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Sample records for acid racemization aar

  1. Amino acid racemization analysis (AAR) as a successful tool for dating Holocene coastal sediments: Stratigraphy of a barrier island spit (Southern Sylt/North Sea)

    NASA Astrophysics Data System (ADS)

    Tillmann, Tanja; Ziehe, Daniel

    2014-05-01

    Dating of Holocene sediments in shallow coastal areas of the German North Sea by conventional techniques is commonly problematic. In particular the marine reservoir effect of radiocarbon means that radiocarbon dating cannot be applied to sediments younger than about 400 years. Amino acid racemization dating (AAR) is a viable alternative for dating young sediments. The method is based on the determination of ratios of D and L amino acid enantiomers in organic matrices of biogenic carbonates. In this study we use AAR as a tool for dating Holocene barrier islands sediments. Based on an AAR derived chronological framework we develop a model of barrier spit accretion which describes the interaction between extreme events, fair weather coastal processes and sedimentary development that constrains the major episodes of barrier island evolution. The stratigraphy was defined using ground-penetrating radar (GPR) surveys complemented by sedimentological coring data. The stratigraphy is then conceptualised in a AAR chronostratigraphic framework to define a chronological order and allow the development of a stratigraphic model of the evolution of Southern Sylt. The AAR data provide high temporal resolution and have been used for dating stages of barrier spit accretion. The time lines are marked as storm surge generated erosion unconformities in the stratigraphic profile. Individual shells and shell fragments of Cerastoderma edule, Mya arenaria, Mytilus edulis and Scrobicularia plana have been accumulated by short-term storm events as shell layers associated with the erosion unconformities and have been dated by AAR. Time lines reveal that the barrier spit accretion occurred episodically, and is dependant on the provided rate of sand delivery. The general trend is that sequences young to the. South. The AAR derived time lines have been verified and correlated by historic maps and sea charts. It is apparent that spit enlargement at this site increased significantly during the

  2. Calibration of amino acid racemization (AAR) kinetics in United States mid-Atlantic Coastal Plain Quaternary mollusks using 87Sr/ 86Sr analyses: Evaluation of kinetic models and estimation of regional Late Pleistocene temperature history

    USGS Publications Warehouse

    Wehmiller, J. F.; Harris, W.B.; Boutin, B.S.; Farrell, K.M.

    2012-01-01

    The use of amino acid racemization (AAR) for estimating ages of Quaternary fossils usually requires a combination of kinetic and effective temperature modeling or independent age calibration of analyzed samples. Because of limited availability of calibration samples, age estimates are often based on model extrapolations from single calibration points over wide ranges of D/L values. Here we present paired AAR and 87Sr/ 86Sr results for Pleistocene mollusks from the North Carolina Coastal Plain, USA. 87Sr/ 86Sr age estimates, derived from the lookup table of McArthur et al. [McArthur, J.M., Howarth, R.J., Bailey, T.R., 2001. Strontium isotopic stratigraphy: LOWESS version 3: best fit to the marine Sr-isotopic curve for 0-509 Ma and accompanying Look-up table for deriving numerical age. Journal of Geology 109, 155-169], provide independent age calibration over the full range of amino acid D/L values, thereby allowing comparisons of alternative kinetic models for seven amino acids. The often-used parabolic kinetic model is found to be insufficient to explain the pattern of racemization, although the kinetic pathways for valine racemization and isoleucine epimerization can be closely approximated with this function. Logarithmic and power law regressions more accurately represent the racemization pathways for all amino acids. The reliability of a non-linear model for leucine racemization, developed and refined over the past 20 years, is confirmed by the 87Sr/ 86Sr age results. This age model indicates that the subsurface record (up to 80m thick) of the North Carolina Coastal Plain spans the entire Quaternary, back to ???2.5Ma. The calibrated kinetics derived from this age model yield an estimate of the effective temperature for the study region of 11??2??C., from which we estimate full glacial (Last Glacial Maximum - LGM) temperatures for the region on the order of 7-10??C cooler than present. These temperatures compare favorably with independent paleoclimate information

  3. Excellent amino acid racemization results from Holocene sand dollars

    NASA Astrophysics Data System (ADS)

    Kosnik, M.; Kaufman, D. S.; Kowalewski, M.; Whitacre, K.

    2015-12-01

    Amino acid racemization (AAR) is widely used as a cost-effective method to date molluscs in time-averaging and taphonomic studies, but it has not been attempted for echinoderms despite their paleobiological importance. Here we demonstrate the feasibility of AAR geochronology in Holocene aged Peronella peronii (Echinodermata: Echinoidea) collected from Sydney Harbour (Australia). Using standard HPLC methods we determined the extent of AAR in 74 Peronella tests and performed replicate analyses on 18 tests. We sampled multiple areas of two individuals and identified the outer edge as a good sampling location. Multiple replicate analyses from the outer edge of 18 tests spanning the observed range of D/Ls yielded median coefficients of variation < 4% for Asp, Phe, Ala, and Glu D/L values, which overlaps with the analytical precision. Correlations between D/L values across 155 HPLC injections sampled from 74 individuals are also very high (pearson r2 > 0.95) for these four amino acids. The ages of 11 individuals spanning the observed range of D/L values were determined using 14C analyses, and Bayesian model averaging was used to determine the best AAR age model. The averaged age model was mainly composed of time-dependent reaction kinetics models (TDK, 71%) based on phenylalanine (Phe, 94%). Modelled ages ranged from 14 to 5539 yrs, and the median 95% confidence interval for the 74 analysed individuals is ±28% of the modelled age. In comparison, the median 95% confidence interval for the 11 calibrated 14C ages was ±9% of the median age estimate. Overall Peronella yields exceptionally high-quality AAR D/L values and appears to be an excellent substrate for AAR geochronology. This work opens the way for time-averaging and taphonomic studies of echinoderms similar to those in molluscs.

  4. Amino acid racemization on planktic foraminifera from the central Arctic Ocean

    NASA Astrophysics Data System (ADS)

    Hanslik, D.; Kaufman, D. S.; Jakobsson, M.

    2009-12-01

    Amino acid racemization (AAR) is the interconversion of amino acids from one chiral form (L - levo) to a mixture of L- and D- (dextro) forms as a function of time and temperature. The extent of AAR in foraminifera shells can be determined by measuring the ratio of D/L amino acids, and can be used as a relative dating method. The technique can also be used to determine numerical ages once the rate of racemization is calibrated for a study area using samples of known ages. In this study sediment cores from the Lomonosov Ridge (88°N) and Morris Jesup Rise (85°N), in the central Arctic Ocean, were analyzed for AAR on monospecific samples of the polar planktic foraminifera Neogloboquadrina pachyderma sinistral. Numerical ages were derived using an equation developed for aspartic and glutamic acids in a previous study on other cores from the Northwind, Mendeleev and Lomonosov ridges, which applies to samples younger than about 150 ka (Kaufman et al., 2008, Paleoceanography 23:PA3224). The calculated AAR ages are in relatively good agreement with 14C ages throughout the range of 14C dating for both of our cores. The core from Morris Jesup Rise includes older sediment beyond the range of 14C dating where ages were inferred from benthic foraminifera events and correlation with other cores with previously published age models. The AAR age for the level of unique occurrence of the benthic foramifera Bulimina aculeata from this core is about 85 ka, which agrees with previous work that assigned this level to MIS 5.1. Beyond about 85 ka, there is a progressively increasing age discrepancy between calculated AAR ages and estimated ages based on benthic foraminifera events. For MIS 5.5, the D/L values for the Epistominella exigua marker are lower in our core than in the cores analyzed by Kaufman et al. (2008). Assuming that this event is a chronostratigraphic marker, then the AAR results suggest that deepwater temperature at our site during MIS 5 was lower than at the other

  5. Amino Acid Racemization and the Preservation of Ancient DNA

    NASA Technical Reports Server (NTRS)

    Poinar, Hendrik N.; Hoss, Matthias

    1996-01-01

    The extent of racemization of aspartic acid, alanine, and leucine provides criteria for assessing whether ancient tissue samples contain endogenous DNA. In samples in which the D/L ratio of aspartic acid exceeds 0.08, ancient DNA sequences could not be retrieved. Paleontological finds from which DNA sequences purportedly millions of years old have been reported show extensive racemization, and the amino acids present are mainly contaminates. An exception is the amino acids in some insects preserved in amber.

  6. Amino acid racemization dating of fossil bones, I. inter-laboratory comparison of racemization measurements

    USGS Publications Warehouse

    Bada, J.L.; Hoopes, E.; Darling, D.; Dungworth, G.; Kessels, H.J.; Kvenvolden, K.A.; Blunt, D.J.

    1979-01-01

    Enantiomeric measurements for aspartic acid, glutamic acid, and alanine in twenty-one different fossil bone samples have been carried out by three different laboratories using different analytical methods. These inter-laboratory comparisons demonstrate that D/L aspartic acid measurements are highly reproducible, whereas the enantiomeric measurements for the other amino acids show a wide variation between the three laboratories. At present, aspartic acid measurements are the most suitable for racemization dating of bone because of their superior analytical precision. ?? 1979.

  7. Assessing amino acid racemization variability in coral intra-crystalline protein for geochronological applications

    NASA Astrophysics Data System (ADS)

    Hendy, Erica J.; Tomiak, Peter J.; Collins, Matthew J.; Hellstrom, John; Tudhope, Alexander W.; Lough, Janice M.; Penkman, Kirsty E. H.

    2012-06-01

    Over 500 Free Amino Acid (FAA) and corresponding Total Hydrolysed Amino Acid (THAA) analyses were completed from eight independently-dated, multi-century coral cores of massive Porites sp. colonies. This dataset allows us to re-evaluate the application of amino acid racemization (AAR) for dating late Holocene coral material, 20 years after Goodfriend et al. (GCA56 (1992), 3847) first showed AAR had promise for developing chronologies in coral cores. This re-assessment incorporates recent method improvements, including measurement by RP-HPLC, new quality control approaches (e.g. sampling and sub-sampling protocols, statistically-based data screening criteria), and cleaning steps to isolate the intra-crystalline skeletal protein. We show that the removal of the extra-crystalline contaminants and matrix protein is the most critical step for reproducible results and recommend a protocol of bleaching samples in NaOCl for 48 h to maximise removal of open system proteins while minimising the induced racemization. We demonstrate that AAR follows closed system behaviour in the intra-crystalline fraction of the coral skeletal proteins. Our study is the first to assess the natural variability in intra-crystalline AAR between colonies, and we use coral cores taken from the Great Barrier Reef, Australia, and Jarvis Island in the equatorial Pacific to explore variability associated with different environmental conditions and thermal histories. Chronologies were developed from THAA Asx D/L, Ala D/L, Glx D/L and FAA Asx D/L for each core and least squares Monte Carlo modelling applied in order to quantify uncertainty of AAR age determinations and assess the level of dating resolution possible over the last 5 centuries. AAR within colonies follow consistent stratigraphic aging. However, there are systematic differences in rates between the colonies, which would preclude direct comparison from one colony to another for accurate age estimation. When AAR age models are developed from

  8. Assessing amino acid racemization variability in coral intra-crystalline protein for geochronological applications.

    PubMed

    Hendy, Erica J; Tomiak, Peter J; Collins, Matthew J; Hellstrom, John; Tudhope, Alexander W; Lough, Janice M; Penkman, Kirsty E H

    2012-06-01

    Over 500 Free Amino Acid (FAA) and corresponding Total Hydrolysed Amino Acid (THAA) analyses were completed from eight independently-dated, multi-century coral cores of massive Porites sp. colonies. This dataset allows us to re-evaluate the application of amino acid racemization (AAR) for dating late Holocene coral material, 20 years after Goodfriend et al. (GCA 56 (1992), 3847) first showed AAR had promise for developing chronologies in coral cores. This re-assessment incorporates recent method improvements, including measurement by RP-HPLC, new quality control approaches (e.g. sampling and sub-sampling protocols, statistically-based data screening criteria), and cleaning steps to isolate the intra-crystalline skeletal protein. We show that the removal of the extra-crystalline contaminants and matrix protein is the most critical step for reproducible results and recommend a protocol of bleaching samples in NaOCl for 48 h to maximise removal of open system proteins while minimising the induced racemization. We demonstrate that AAR follows closed system behaviour in the intra-crystalline fraction of the coral skeletal proteins. Our study is the first to assess the natural variability in intra-crystalline AAR between colonies, and we use coral cores taken from the Great Barrier Reef, Australia, and Jarvis Island in the equatorial Pacific to explore variability associated with different environmental conditions and thermal histories. Chronologies were developed from THAA Asx D/L, Ala D/L, Glx D/L and FAA Asx D/L for each core and least squares Monte Carlo modelling applied in order to quantify uncertainty of AAR age determinations and assess the level of dating resolution possible over the last 5 centuries. AAR within colonies follow consistent stratigraphic aging. However, there are systematic differences in rates between the colonies, which would preclude direct comparison from one colony to another for accurate age estimation. When AAR age models are developed

  9. Amino acid racemization dating of marine shells: A mound of possibilities.

    PubMed

    Demarchi, Beatrice; Williams, Matt G; Milner, Nicky; Russell, Nicola; Bailey, Geoff; Penkman, Kirsty

    2011-07-01

    Shell middens are one of the most important and widespread indicators for human exploitation of marine resources and occupation of coastal environments. Establishing an accurate and reliable chronology for these deposits has fundamental implications for understanding the patterns of human evolution and dispersal. This paper explores the potential application of a new methodology of amino acid racemization (AAR) dating of shell middens and describes a simple protocol to test the suitability of different molluscan species. This protocol provides a preliminary test for the presence of an intracrystalline fraction of proteins (by bleaching experiments and subsequent heating at high temperature), checking the closed system behaviour of this fraction during diagenesis. Only species which pass both tests can be considered suitable for further studies to obtain reliable age information. This amino acid geochronological technique is also applied to midden deposits at two latitudinal extremes: Northern Scotland and the Southern Red Sea. Results obtained in this study indicate that the application of this new method of AAR dating of shells has the potential to aid the geochronological investigation of shell mounds in different areas of the world. PMID:21776187

  10. Amino acid racemization dating of marine shells: A mound of possibilities

    PubMed Central

    Demarchi, Beatrice; Williams, Matt G.; Milner, Nicky; Russell, Nicola; Bailey, Geoff; Penkman, Kirsty

    2011-01-01

    Shell middens are one of the most important and widespread indicators for human exploitation of marine resources and occupation of coastal environments. Establishing an accurate and reliable chronology for these deposits has fundamental implications for understanding the patterns of human evolution and dispersal. This paper explores the potential application of a new methodology of amino acid racemization (AAR) dating of shell middens and describes a simple protocol to test the suitability of different molluscan species. This protocol provides a preliminary test for the presence of an intracrystalline fraction of proteins (by bleaching experiments and subsequent heating at high temperature), checking the closed system behaviour of this fraction during diagenesis. Only species which pass both tests can be considered suitable for further studies to obtain reliable age information. This amino acid geochronological technique is also applied to midden deposits at two latitudinal extremes: Northern Scotland and the Southern Red Sea. Results obtained in this study indicate that the application of this new method of AAR dating of shells has the potential to aid the geochronological investigation of shell mounds in different areas of the world. PMID:21776187

  11. A critical evaluation of the application of amino acid racemization to geochronology and geothermometry

    NASA Technical Reports Server (NTRS)

    Williams, K. M.; Smith, G. G.

    1977-01-01

    Attempts have been made to determine the age of biological samples by measuring the racemization of amino acids in protein samples. The pitfalls and inherent complications in diagenetic racemization studies are reviewed, and recent advances in improving techniques are outlined. Methodological topics include isolation of amino acids from geological samples, resolution of amino acid enantiomers, and the effects of acid hydrolysis. The theory and kinetics of amino acid racemization are discussed with attention to the derivation of the rate expression for amino acid racemization, isoleucine and the equilibrium constant, the mechanism of amino acid racemization, the racemization of 'bound' versus 'free' amino acids, and factors affecting the racemization rates of free amino acids in aqueous solution. Applications of amino acid racemization kinetics to geochronology is considered with reference to shells, marine sediments, and bones. Potential complications include heating and diagenesis, diagenetic formation of amino acids, the effect of clays, species effect, and contamination.

  12. The small RNA Aar in Acinetobacter baylyi: a putative regulator of amino acid metabolism.

    PubMed

    Schilling, Dominik; Findeiss, Sven; Richter, Andreas S; Taylor, Jennifer A; Gerischer, Ulrike

    2010-09-01

    Small non-coding RNAs (sRNAs) are key players in prokaryotic metabolic circuits, allowing the cell to adapt to changing environmental conditions. Regulatory interference by sRNAs in cellular metabolism is often facilitated by the Sm-like protein Hfq. A search for novel sRNAs in A. baylyi intergenic regions was performed by a biocomputational screening. One candidate, Aar, encoded between trpS and sucD showed Hfq dependency in Northern blot analysis. Aar was expressed strongly during stationary growth phase in minimal medium; in contrast, in complex medium, strongest expression was in the exponential growth phase. Whereas over-expression of Aar in trans did not affect bacterial growth, seven mRNA targets predicted by two in silico approaches were upregulated in stationary growth phase. All seven mRNAs are involved in A. baylyi amino acid metabolism. A putative binding site for Lrp, the global regulator of branched-chain amino acids in E. coli, was observed within the aar gene. Both facts imply an Aar participation in amino acid metabolism. PMID:20559624

  13. Amino acid racemization on Mars: implications for the preservation of biomolecules from an extinct martian biota

    NASA Technical Reports Server (NTRS)

    Bada, J. L.; McDonald, G. D.; Miller, S. L. (Principal Investigator)

    1995-01-01

    Using kinetic data, we have estimated the racemization half-lives and times for total racemization of amino acids under conditions relevant to the surface of Mars. Amino acids from an extinct martian biota maintained in a dry, cold (<250 K) environment would not have racemized significantly over the lifetime of the planet. Racemization would have taken place in environments where liquid water was present even for time periods of only a few million years following biotic extinction. The best preservation of both amino acid homochirality and nucleic acid genetic information associated with extinct martian life would be in the polar regions.

  14. Application of the DCP model to a metastable racemate of mandelic acid

    NASA Astrophysics Data System (ADS)

    Pauchet, M.; Coquerel, G.

    2004-12-01

    Mandelic acid is a chiral molecule often used as a resolving agent in the separation of enantiomers. To date, three different crystalline structures have been characterized: the pure enantiomer and two polymorphs of the racemic compound. However, the metastable racemic and the pure enantiomeric crystal structures share analogies. Because of these similarities, the DCP model has been applied to rebuild the metastable racemic compound by recombining a periodic fragment extracted from the crystal structure of the enantiomer. As computations reveal another very similar crystal lattice of the racemic compound, possible disorder and/or twining and/or polytypism are surmised.

  15. Amino Acid Racemization in Pseudomonas putida KT2440

    PubMed Central

    Radkov, Atanas D.

    2013-01-01

    d-Amino acids have been shown to play an increasingly diverse role in bacterial physiology, yet much remains to be learned about their synthesis and catabolism. Here we used the model soil- and rhizosphere-dwelling organism Pseudomonas putida KT2440 to elaborate on the genomics and enzymology of d-amino acid metabolism. P. putida KT2440 catabolized the d-stereoisomers of lysine, phenylalanine, arginine, alanine, and hydroxyproline as the sole carbon and nitrogen sources. With the exception of phenylalanine, each of these amino acids was racemized by P. putida KT2440 enzymes. Three amino acid racemases were identified from a genomic screen, and the enzymes were further characterized in vitro. The putative biosynthetic alanine racemase Alr showed broad substrate specificity, exhibiting measurable racemase activity with 9 of the 19 chiral amino acids. Among these amino acids, activity was the highest with lysine, and the kcat/Km values with l- and d-lysine were 3 orders of magnitude greater than the kcat/Km values with l- and d-alanine. Conversely, the putative catabolic alanine racemase DadX showed narrow substrate specificity, clearly preferring only the alanine stereoisomers as the substrates. However, DadX did show 6- and 9-fold higher kcat/Km values than Alr with l- and d-alanine, respectively. The annotated proline racemase ProR of P. putida KT2440 showed negligible activity with either stereoisomer of the 19 chiral amino acids but exhibited strong epimerization activity with hydroxyproline as the substrate. Comparative genomic analysis revealed differences among pseudomonads with respect to alanine racemase genes that may point to different roles for these genes among closely related species. PMID:23995642

  16. Amino acid deprivation induces CREBZF/Zhangfei expression via an AARE-like element in the promoter.

    PubMed

    Zhang, Yani; Jin, Yaping; Williams, Tegan A; Burtenshaw, Sally M; Martyn, Amanda C; Lu, Rui

    2010-01-15

    CREBZF (also called ZF or Zhangfei) is a basic region-leucine zipper transcription factor that has been implicated in the herpesvirus infection cycle and related cellular processes. Since ATF4 is known to play a key role in cellular responses to various ER stresses as well as amino acid deprivation, we sought to examine the potential involvement of CREBZF in the amino acid response (AAR). We found that the CREBZF protein was induced by amino acid deprivation in the canine MDCK cells. We subsequently cloned a canine CREBZF promoter region (-1767bp to +1bp) that responds to amino acid limitation. Using deletion mapping and site-directed mutagenesis, we identified a 9-bp sequence 5'-ATTCACTCA-3' in the promoter (-1227 to -1219), deletion of which resulted in a complete loss of inducibility by amino acid deprivation. This sequence is similar to the known amino acid response elements (AAREs) found in other AAR-inducible genes, such as CHOP (C/EBP homologous protein, also known as GADD153). These results suggest that CREBZF may be an amino acid stress sensor. Considering the AARE-like sequence found in CREBZF and other similarities between CREBZF and CHOP, we postulate that CREBZF and CHOP may be two sensors that regulate different yet related signaling pathways governing the AAR. PMID:20026304

  17. The Formation of Racemic Amino Acids by UV Photolysis of Interstellar Ice Analogs

    NASA Technical Reports Server (NTRS)

    Bernstein, Max P.; Dworkin, Jason P.; Sandford, Scott A.; Cooper, George; Allamandola, Louis J.; DeVincenzi, Donald (Technical Monitor)

    2001-01-01

    Small biologically relevant organic molecules including the amino acids glycine, alanine, and marine were formed in the laboratory by the UV (Ultraviolet) photolysis of realistic interstellar ice analogs, composed primarily of H2O, and including CH3OH, NH3, and HCN, under interstellar conditions. N-formyl glycine, cycloserine (4-amino-3-isoxazolidinone), and glycerol were detected before hydrolysis, and glycine, racemic alanine, racemic marine, glycerol, ethanolamine, and glyceric acid were found after hydrolysis. This suggests that some meteoritic amino acids (and other molecules) may be the direct result of interstellar ice photochemistry, expanding the current paradigm that they formed by reactions in liquid water on meteorite parent bodies.

  18. Are the Crystal Structures of Enantiopure and Racemic Mandelic Acids Determined by Kinetics or Thermodynamics?

    PubMed

    Hylton, Rebecca K; Tizzard, Graham J; Threlfall, Terence L; Ellis, Amy L; Coles, Simon J; Seaton, Colin C; Schulze, Eric; Lorenz, Heike; Seidel-Morgenstern, Andreas; Stein, Matthias; Price, Sarah L

    2015-09-01

    Mandelic acids are prototypic chiral molecules where the sensitivity of crystallized forms (enantiopure/racemic compound/polymorphs) to both conditions and substituents provides a new insight into the factors that may allow chiral separation by crystallization. The determination of a significant number of single crystal structures allows the analysis of 13 enantiopure and 30 racemic crystal structures of 21 (F/Cl/Br/CH3/CH3O) substituted mandelic acid derivatives. There are some common phenyl packing motifs between some groups of racemic and enantiopure structures, although they show very different hydrogen-bonding motifs. The computed crystal energy landscape of 3-chloromandelic acid, which has at least two enantiopure and three racemic crystal polymorphs, reveals that there are many more possible structures, some of which are predicted to be thermodynamically more favorable as well as slightly denser than the known forms. Simulations of mandelic acid dimers in isolation, water, and toluene do not differentiate between racemic and enantiopure dimers and also suggest that the phenyl ring interactions play a major role in the crystallization mechanism. The observed crystallization behavior of mandelic acids does not correspond to any simple "crystal engineering rules" as there is a range of thermodynamically feasible structures with no distinction between the enantiopure and racemic forms. Nucleation and crystallization appear to be determined by the kinetics of crystal growth with a statistical bias, but the diversity of the mandelic acid crystallization behavior demonstrates that the factors that influence the kinetics of crystal nucleation and growth are not yet adequately understood. PMID:26244445

  19. Sediment accumulation, stratigraphic order, and the extent of time-averaging in lagoonal sediments: a comparison of 210Pb and 14C/amino acid racemization chronologies

    NASA Astrophysics Data System (ADS)

    Kosnik, Matthew A.; Hua, Quan; Kaufman, Darrell S.; Zawadzki, Atun

    2015-03-01

    Carbon-14 calibrated amino acid racemization (14C/AAR) data and lead-210 (210Pb) data are used to examine sediment accumulation rates, stratigraphic order, and the extent of time-averaging in sediments collected from the One Tree Reef lagoon (southern Great Barrier Reef, Australia). The top meter of lagoonal sediment preserves a stratigraphically ordered deposit spanning the last 600 yrs. Despite different assumptions, the 210Pb and 14C/AAR chronologies are remarkably similar indicating consistency in sedimentary processes across sediment grain sizes spanning more than three orders of magnitude (0.1-10 mm). Estimates of long-term sediment accumulation rates range from 2.2 to 1.2 mm yr-1. Molluscan time-averaging in the taphonomically active zone is 19 yrs, whereas below the depth of final burial (~15 cm), it is ~110 yrs/5 cm layer. While not a high-resolution paleontological record, this reef lagoon sediment is suitable for paleoecological studies spanning the period of Western colonization and development. This sedimentary deposit, and others like it, should be useful, albeit not ideal, for quantifying anthropogenic impacts on coral reef systems.

  20. Age estimation in forensic sciences: Application of combined aspartic acid racemization and radiocarbon analysis

    SciTech Connect

    Alkass, K; Buchholz, B A; Ohtani, S; Yamamoto, T; Druid, H; Spalding, S L

    2009-11-02

    Age determination of unknown human bodies is important in the setting of a crime investigation or a mass disaster, since the age at death, birth date and year of death, as well as gender, can guide investigators to the correct identity among a large number of possible matches. Traditional morphological methods used by anthropologists to determine age are often imprecise, whereas chemical analysis of tooth dentin, such as aspartic acid racemization has shown reproducible and more precise results. In this paper we analyze teeth from Swedish individuals using both aspartic acid racemization and radiocarbon methodologies. The rationale behind using radiocarbon analysis is that above-ground testing of nuclear weapons during the cold war (1955-1963) caused an extreme increase in global levels of carbon-14 ({sup 14}C) which have been carefully recorded over time. Forty-four teeth from 41 individuals were analyzed using aspartic acid racemization analysis of tooth crown dentin or radiocarbon analysis of enamel and ten of these were split and subjected to both radiocarbon and racemization analysis. Combined analysis showed that the two methods correlated well (R2=0.66, p < 0.05). Radiocarbon analysis showed an excellent precision with an overall absolute error of 0.6 {+-} 04 years. Aspartic acid racemization also showed a good precision with an overall absolute error of 5.4 {+-} 4.2 years. Whereas radiocarbon analysis gives an estimated year of birth, racemization analysis indicates the chronological age of the individual at the time of death. We show how these methods in combination can also assist in the estimation of date of death of an unidentified victim. This strategy can be of significant assistance in forensic casework involving dead victim identification.

  1. A critical evaluation of the application of amino acid racemization to geochronology and geothermometry.

    PubMed

    Williams, K M; Smith, G G

    1977-08-01

    In this review we have critically evaluated the application of the diagenetic racemization of amino acids to geochronology and geothermometry. Although there has been enthusiastic support given to this new method, it is our opinion that recent developments suggest a more cautious approach. We have discussed the pitfalls and inhereent complications, while outlining the advances which have been accomplished. We conclude that this is an innovative approach which will add valuable information to the scientific literature. However, since our fundamental understanding of diagnetic racemization is still limited, many of the age and paleotemperature estimates which have been assigned to fossil specimens may be unreliable. PMID:335314

  2. Amino acid racemization reveals differential protein turnover in osteoarthritic articular and meniscal cartilages

    PubMed Central

    Stabler, Thomas V; Byers, Samuel S; Zura, Robert D; Kraus, Virginia Byers

    2009-01-01

    Introduction Certain amino acids within proteins have been reported to change from the L form to the D form over time. This process is known as racemization and is most likely to occur in long-lived low-turnover tissues such as normal cartilage. We hypothesized that diseased tissue, as found in an osteoarthritic (OA) joint, would have increased turnover reflected by a decrease in the racemized amino acid content. Methods Using high-performance liquid chromatography methods, we quantified the L and D forms of amino acids reported to racemize in vivo on a biological timescale: alanine, aspartate (Asp), asparagine (Asn), glutamate, glutamine, isoleucine, leucine (Leu), and serine (Ser). Furthermore, using a metabolically inactive control material (tooth dentin) and a control material with normal metabolism (normal articular cartilage), we developed an age adjustment in order to make inferences about the state of protein turnover in cartilage and meniscus. Results In the metabolically inactive control material (n = 25, ages 13 to 80 years) and the normal metabolizing control material (n = 19, ages 17 to 83 years), only Asp + Asn (Asx), Ser, and Leu showed a significant change (increase) in racemization with age (P < 0.01). The age-adjusted proportions of racemized to total amino acid (D/D+L expressed as a percentage of the control material) for Asx, Ser, and Leu when compared with the normal articular cartilage control were 97%, 74%, and 73% in OA meniscal cartilage and 97%, 70%, and 78% in OA articular cartilage. We also observed lower amino acid content in OA articular and meniscal cartilages compared with normal articular cartilage as well as a loss of total amino acids with age in the OA meniscal but not the OA articular cartilage. Conclusions These data demonstrate comparable anabolic responses for non-lesioned OA articular cartilage and OA meniscal cartilage but an excess of catabolism over anabolism for the meniscal cartilage. PMID:19267899

  3. Racemization in Reverse: Evidence that D-Amino Acid Toxicity on Earth Is Controlled by Bacteria with Racemases

    PubMed Central

    Zhang, Gaosen; Sun, Henry J.

    2014-01-01

    D-amino acids are toxic for life on Earth. Yet, they form constantly due to geochemical racemization and bacterial growth (the cell walls of which contain D-amino acids), raising the fundamental question of how they ultimately are recycled. This study provides evidence that bacteria use D-amino acids as a source of nitrogen by running enzymatic racemization in reverse. Consequently, when soils are inundated with racemic amino acids, resident bacteria consume D- as well as L-enantiomers, either simultaneously or sequentially depending on the level of their racemase activity. Bacteria thus protect life on Earth by keeping environments D-amino acid free. PMID:24647559

  4. Amino acid racemization in amber-entombed insects: implications for DNA preservation

    NASA Technical Reports Server (NTRS)

    Bada, J. L.; Wang, X. S.; Poinar, H. N.; Paabo, S.; Poinar, G. O.

    1994-01-01

    DNA depurination and amino acid racemization take place at similar rates in aqueous solution at neutral pH. This relationship suggests that amino acid racemization may be useful in accessing the extent of DNA chain breakage in ancient biological remains. To test this suggestion, we have investigated the amino acids in insects entombed in fossilized tree resins ranging in age from <100 years to 130 million years. The amino acids present in 40 to 130 million year old amber-entombed insects resemble those in a modern fly and are probably the most ancient, unaltered amino acids found so far on Earth. In comparison to other geochemical environments on the surface of the Earth, the amino acid racemization rate in amber insect inclusions is retarded by a factor of >10(4). These results suggest that in amber insect inclusions DNA depurination rates would also likely be retarded in comparison to aqueous solution measurements, and thus DNA fragments containing many hundreds of base pairs should be preserved. This conclusion is consistent with the reported successful retrieval of DNA sequences from amber-entombed organisms.

  5. Comparison of acid anhydrides with carboxylic acids in enantioselective enzymatic esterification of racemic menthol.

    PubMed

    Xu, J; Zhu, J; Kawamoto, T; Atsuo, T; Hu, Y

    1997-01-01

    Optical resolution of racemic menthol has been efficiently achieved by lipase-catalyzed enantioselective esterification in an organic solvent. The performance of the reaction using an acid anhydride as an acyl donor was compared with that using its corresponding free acid. The reactivities of acid anhydrides were found to be higher than their corresponding free acids, but acid anhydrides were also found to be easily hydrolyzed into free acids under the catalysis of the same enzyme. The existence of a too-high concentration of an acid anhydride in a micro-aqueous reaction system will cause dehydration and thus deactivation of the enzyme, and will enhance non-selective esterification of a chiral alcohol, which will reduce the optical purity of the product. All these drawbacks, however, could be effectively overcome in a semi-batch reaction system into which propionic anhydride was continuously fed. This system showed some advantages over a batch reaction system using free propionic acid: the reaction time of dl-menthol was shortened by half, the stability of the enzyme was much enhanced, and the optical purity of the product (l-menthyl ester) was kept at a similarly high level (> 98% ee). PMID:9631262

  6. Patterns of racemization and epimerization of amino acids in land snail shells over the course of the Holocene

    SciTech Connect

    Goodfriend, G.A. )

    1991-01-01

    The patterns of racemization of six amino acids and of epimerization of isoleucine over the course of the Holocene were studied in a series of 38 radiocarbon-dated samples of the land snail Trochoidea seetzeni from the Negev Desert in southern Israel. The D/L ratios of each of the amino acids show a strong correlation with age (r = 0.84-0.94) and thus good age predictive ability. The patterns in faster-racemizing amino acids do not conform to first-order kinetics. Transformation to parabolic kinetics linearizes these faster-racemizing amino acids, except for aspartic acid (which shows a very high initial rate of racemization). After transformation, each amino acid shows an equally good correlation with age (r = 0.91-0.93). The D/L ratios of the various amino acids covary very strongly, even after the covariation due to sample age is removed from the data set. Thus, analysis of more than one amino acid provides largely redundant information on sample age. Nevertheless, because of differences in racemization rates, some amino acids provide better time resolution in different time ranges - aspartic acid is especially useful for very young samples, and glutamic acid and isoleucine for older samples. Neither the depth of burial of the samples nor the burial mode appears to affect the rate of racemization or epimerization.

  7. Crystallization and sublimation of non-racemic mixtures of natural amino acids: a path towards homochirality

    NASA Astrophysics Data System (ADS)

    Tarasevych, Arkadii V.; Guillemin, Jean-Claude

    2012-07-01

    Homochirality of biologically important molecules such as amino acids and sugars is a prerequisite for the origin of life. There are different forces or mechanisms in the Universe to trigger off the primary imbalance in the enantiomeric ratio. Very likely the initial bias of one type of enantiomers over the other on Earth was arisen from the inflow of extraterrestrial matter (carbonaceous meteorites). The phase transitions (crystallization, sublimation) of non-racemic mixtures of enantiomers are ones of the most probable mechanisms for the homochirogenesis[1]. The sublimation, almost uninvestigated subject and forgotten for 30 years, revealed recently a pathway to the enantioenrichment of natural amino acids[2]. Starting from a mixture with a low content of an enantiopure amino acid a partial sublimation gives a considerable enrichment. In our further experiments we combined two first-order phase transitions of amino acid(s) mixtures: crystallization and sublimation. The results show the possibility of the transfer of enantiopurity between different amino acids[3]. Subliming a crystallized mixture of racemic amino acids with an enantiopure one we found that the sublimate is a non-racemic mixture of the same handedness for all components. The significance of the studies can be realized taking into account that just 5 of 22 proteinogenic amino acids are able to homochiral self-organization. The relevance of these studies to the Prebiotic Earth and to the evolution of the single handedness of biological molecules will be discussed. [1] Blackmond, Phil. Trans. R. Soc. B 2011, 366, 2878. [2] Guillemin et al., Chem. Commun. 2010 , 46, 1482. [3] Tarasevych, Guillemin et al., submitted.

  8. Comparative analysis of aspartic acid racemization methods using whole-tooth and dentin samples.

    PubMed

    Sakuma, Ayaka; Ohtani, Susumu; Saitoh, Hisako; Iwase, Hirotaro

    2012-11-30

    One way to estimate biological age is to use the aspartic acid (Asp) racemization method. Although this method has been performed mostly using enamel and dentin, we investigated whether an entire tooth can be used for age estimation. This study used 12 pairs of canines extracted from both sides of the mandible of 12 individuals of known age. From each pair, one tooth was used as a dentin sample and the other as a whole-tooth sample. Amino acids were extracted from each sample, and the integrated peak areas of D-Asp and L-Asp were determined using a gas chromatograph/mass spectrometer. Statistical analysis was performed using the D/L-Asp ratio. Furthermore, teeth from two unidentified bodies, later identified as Japanese and Brazilian, were examined in the same manner. Results showed that the D/L ratios of whole-tooth samples were higher overall than those of dentin samples. The correlation coefficient between the D/L ratios of dentin samples and their age was r=0.98, and that of the whole-tooth samples was r=0.93. The difference between estimated age and actual chronological age was -0.116 and -6.86 years in the Japanese and Brazilian cases, respectively. The use of whole teeth makes the racemization technique easier and can standardize the sampling site. Additionally, using only a few tooth samples per analysis made it possible to reanalyze known-age samples. Although the difficulty in obtaining a proper control sample has prevented racemization from being widely used, the method described here not only ensures the availability of a control tooth, but also enables the teeth to be used for other purposes such as DNA analysis. The use of a whole tooth will increase the application of the racemization technique for age determination. PMID:22989598

  9. Does aspartic acid racemization constrain the depth limit of the subsurface biosphere?

    PubMed

    Onstott, T C; Magnabosco, C; Aubrey, A D; Burton, A S; Dworkin, J P; Elsila, J E; Grunsfeld, S; Cao, B H; Hein, J E; Glavin, D P; Kieft, T L; Silver, B J; Phelps, T J; van Heerden, E; Opperman, D J; Bada, J L

    2014-01-01

    Previous studies of the subsurface biosphere have deduced average cellular doubling times of hundreds to thousands of years based upon geochemical models. We have directly constrained the in situ average cellular protein turnover or doubling times for metabolically active micro-organisms based on cellular amino acid abundances, D/L values of cellular aspartic acid, and the in vivo aspartic acid racemization rate. Application of this method to planktonic microbial communities collected from deep fractures in South Africa yielded maximum cellular amino acid turnover times of ~89 years for 1 km depth and 27 °C and 1-2 years for 3 km depth and 54 °C. The latter turnover times are much shorter than previously estimated cellular turnover times based upon geochemical arguments. The aspartic acid racemization rate at higher temperatures yields cellular protein doubling times that are consistent with the survival times of hyperthermophilic strains and predicts that at temperatures of 85 °C, cells must replace proteins every couple of days to maintain enzymatic activity. Such a high maintenance requirement may be the principal limit on the abundance of living micro-organisms in the deep, hot subsurface biosphere, as well as a potential limit on their activity. The measurement of the D/L of aspartic acid in biological samples is a potentially powerful tool for deep, fractured continental and oceanic crustal settings where geochemical models of carbon turnover times are poorly constrained. Experimental observations on the racemization rates of aspartic acid in living thermophiles and hyperthermophiles could test this hypothesis. The development of corrections for cell wall peptides and spores will be required, however, to improve the accuracy of these estimates for environmental samples. PMID:24289240

  10. Does aspartic acid racemization constrain the depth limit of the subsurface biosphere?

    SciTech Connect

    Onstott, T. C.; Aubrey, A.D.; Kieft, T L; Silver, B J; Phelps, Tommy Joe; Van Heerden, E.; Opperman, D. J.; Bada, J L.

    2014-01-01

    Previous studies of the subsurface biosphere have deduced average cellular doubling times of hundreds to thousands of years based upon geochemical models. We have directly constrained the in situ average cellular protein turnover or doubling times for metabolically active micro-organisms based on cellular amino acid abundances, D/L values of cellular aspartic acid, and the in vivo aspartic acid racemization rate. Application of this method to planktonic microbial communities collected from deep fractures in South Africa yielded maximum cellular amino acid turnover times of ~89 years for 1 km depth and 27 C and 1 2 years for 3 km depth and 54 C. The latter turnover times are much shorter than previously estimated cellular turnover times based upon geochemical arguments. The aspartic acid racemization rate at higher temperatures yields cellular protein doubling times that are consistent with the survival times of hyperthermophilic strains and predicts that at temperatures of 85 C, cells must replace proteins every couple of days to maintain enzymatic activity. Such a high maintenance requirement may be the principal limit on the abundance of living micro-organisms in the deep, hot subsurface biosphere, as well as a potential limit on their activity. The measurement of the D/L of aspartic acid in biological samples is a potentially powerful tool for deep, fractured continental and oceanic crustal settings where geochemical models of carbon turnover times are poorly constrained. Experimental observations on the racemization rates of aspartic acid in living thermophiles and hyperthermophiles could test this hypothesis. The development of corrections for cell wall peptides and spores will be required, however, to improve the accuracy of these estimates for environmental samples.

  11. Does Aspartic Acid Racemization Constrain the Depth Limit of the Subsurface Biosphere?

    NASA Technical Reports Server (NTRS)

    Onstott, T C.; Magnabosco, C.; Aubrey, A. D.; Burton, A. S.; Dworkin, J. P.; Elsila, J. E.; Grunsfeld, S.; Cao, B. H.; Hein, J. E.; Glavin, D. P.; Kieft, T. L.; Silver, B. J.; Phelps, T. J.; Heerden, E. Van; Opperman, D. J.; Bada, J. L.

    2013-01-01

    Previous studies of the subsurface biosphere have deduced average cellular doubling times of hundreds to thousands of years based upon geochemical models. We have directly constrained the in situ average cellular protein turnover or doubling times for metabolically active micro-organisms based on cellular amino acid abundances, D/L values of cellular aspartic acid, and the in vivo aspartic acid racemization rate. Application of this method to planktonic microbial communities collected from deep fractures in South Africa yielded maximum cellular amino acid turnover times of approximately 89 years for 1 km depth and 27 C and 1-2 years for 3 km depth and 54 C. The latter turnover times are much shorter than previously estimated cellular turnover times based upon geochemical arguments. The aspartic acid racemization rate at higher temperatures yields cellular protein doubling times that are consistent with the survival times of hyperthermophilic strains and predicts that at temperatures of 85 C, cells must replace proteins every couple of days to maintain enzymatic activity. Such a high maintenance requirement may be the principal limit on the abundance of living micro-organisms in the deep, hot subsurface biosphere, as well as a potential limit on their activity. The measurement of the D/L of aspartic acid in biological samples is a potentially powerful tool for deep, fractured continental and oceanic crustal settings where geochemical models of carbon turnover times are poorly constrained. Experimental observations on the racemization rates of aspartic acid in living thermophiles and hyperthermophiles could test this hypothesis. The development of corrections for cell wall peptides and spores will be required, however, to improve the accuracy of these estimates for environmental samples.

  12. Aspartic acid racemization dating of Holocene brachiopods and bivalves from the southern Brazilian shelf, South Atlantic

    NASA Astrophysics Data System (ADS)

    Barbour Wood, Susan L.; Krause, Richard A.; Kowalewski, Michał; Wehmiller, John; Simões, Marcello G.

    2006-09-01

    The extent of racemization of aspartic acid (Asp) has been used to estimate the ages of 9 shells of the epifaunal calcitic brachiopod Bouchardia rosea and 9 shells of the infaunal aragonitic bivalve Semele casali. Both taxa were collected concurrently from the same sites at depths of 10 m and 30 m off the coast of Brazil. Asp D/L values show an excellent correlation with radiocarbon age at both sites and for both taxa ( r2Site 9 B. rosea = 0.97, r2Site 1 B. rosea = 0.997, r2Site 9 S. casali = 0.9998, r2Site 1 S. casali = 0.93). The Asp ratios plotted against reservoir-corrected AMS radiocarbon ages over the time span of multiple millennia can thus be used to develop reliable and precise geochronologies not only for aragonitic mollusks (widely used for dating previously), but also for calcitic brachiopods. At each collection site, Bouchardia specimens display consistently higher D/L values than specimens of Semele. Thermal differences between sites are also notable and in agreement with theoretical expectations, as extents of racemization for both taxa are greater at the warmer, shallower site than at the cooler, deeper one. In late Holocene marine settings, concurrent time series of aragonitic and calcitic shells can be assembled using Asp racemization dating, and parallel multi-centennial to multi-millennial records can be developed simultaneously for multiple biomineral systems.

  13. Enantioconvergent Nucleophilic Substitution Reaction of Racemic Alkyne-Dicobalt Complex (Nicholas Reaction) Catalyzed by Chiral Brønsted Acid.

    PubMed

    Terada, Masahiro; Ota, Yusuke; Li, Feng; Toda, Yasunori; Kondoh, Azusa

    2016-08-31

    Catalytic enantioselective syntheses enable a practical approach to enantioenriched molecules. While most of these syntheses have been accomplished by reaction at the prochiral sp(2)-hybridized carbon atom, little attention has been paid to enantioselective nucleophilic substitution at the sp(3)-hybridized carbon atom. In particular, substitution at the chiral sp(3)-hybridized carbon atom of racemic electrophiles has been rarely exploited. To establish an unprecedented enantioselective substitution reaction of racemic electrophiles, enantioconvergent Nicholas reaction of an alkyne-dicobalt complex derived from racemic propargylic alcohol was developed using a chiral phosphoric acid catalyst. In the present enantioconvergent process, both enantiomers of the racemic alcohol were transformed efficiently to a variety of thioethers with high enantioselectivity. The key to achieving success is dynamic kinetic asymmetric transformation (DYKAT) of enantiomeric cationic intermediates generated via dehydroxylation of the starting racemic alcohol under the influence of the chiral phosphoric acid catalyst. The present fascinating DYKAT involves the efficient racemization of these enantiomeric intermediates and effective resolution of these enantiomers through utilization of the chiral conjugate base of the phosphoric acid. PMID:27490239

  14. Rhodium-catalysed asymmetric allylic arylation of racemic halides with arylboronic acids

    NASA Astrophysics Data System (ADS)

    Sidera, Mireia; Fletcher, Stephen P.

    2015-11-01

    Csp2-Csp2 cross-coupling reactions between arylboronic acid and aryl halides are widely used in both academia and industry and are strategically important in the development of new agrochemicals and pharmaceuticals. Csp2-Csp3 cross-coupling reactions have been developed, but enantioselective variations are rare and simply retaining the stereochemistry is a problem. Here we report a highly enantioselective Csp2-Csp3 bond-forming method that couples arylboronic acids to racemic allyl chlorides. Both enantiomers of a cyclic chloride are converted into a single enantiomer of product via a dynamic kinetic asymmetric transformation. This Rh-catalysed method uses readily available and inexpensive building blocks and is mild and broadly applicable. For electron-deficient, electron-rich or ortho-substituted boronic acids better results are obtained with racemic allyl bromides. Oxygen substitution in the allyl halide is tolerated and the products can be functionalized to provide diverse building blocks. The approach fills a significant gap in the methods for catalytic asymmetric synthesis.

  15. Enigmatic Isovaline: Investigating the Stability, Racemization, and Formation of a Non-biological Meteoritic Amino Acid

    NASA Technical Reports Server (NTRS)

    Hudson, Reggie; Moore, Marla; Lewis, Ariel; Dworkin, Jason

    2008-01-01

    Among the Murchison meteoritic amino acids, isovaline stands out as being both nonbiological (non-protein) and having a relatively high abundance. While approximately equal amounts of D- and L-isovaline have been reported in Murchison and other CM meteorites, the molecule's structure appears to prohibit its racemization in aqueous solutions. We recently have investigated the low-temperature solid-phase chemistry of both isovaline and valine with an eye toward each molecule's formation, stability, and possible interconversions of D and L enantiomers. Ion-irradiated isovaline- and valinecontaining ices were examined by IR spectroscopy and highly-sensitive liquid chromatography/time-of-flight mass spectral methods to assess both amino acid destruction and racemization. Samples were studied in the presence and in the absence of water-ice, and the destruction of both isovaline and valine was measured as a function of radiation dose. In addition, we have undertaken experiments to synthesize isovaline, valine, and their amino acid isomers by solid-phase radiation-chemical pathways other than the oft-invoked Strecker process. This presentation will review and summarize some of our recent findings. -- Our work has been supported by a grant to the Goddard Center for Astrobiology through the NASA Astrobiology Institute. Experiments were performed in the Cosmic Ice Laboratory (RLH, MHM, AL) and the Astrobiology Analytical Laboratory (JPD, DPG) at the NASA Goddard Space Flight Center.

  16. Use Of Amino Acid Racemization To Investigate The Metabolic Activity Of ?Dormant? Microorganisms In Siberian Permafrost

    NASA Astrophysics Data System (ADS)

    Tsapin, A.; McDonald, G.

    2002-12-01

    search for extraterrestrial life or its remnants is based on studying the most probable environments in which life (extant or extinct) may be found, and determining the maximum period of time over which such life could be preserved. The terrestrial permafrost, inhabited by cold adapted microbes, can be considered as an extraterrestrial analog environment. The cells and their metabolic end-products in Earth's permafrost can be used in the search for possible ecosystems and potential inhabitants on extraterrestrial cryogenic bodies. The study of microorganisms (or their remnants) that were buried for a few million years in permafrost provides us with a unique opportunity to determine the long-term viability of (micro)organisms. We have analyzed the degree of racemization of aspartic acid in permafrost samples from Northern Siberia (Brinton et al. 2002, Astrobiology 2, 77), an area from which microorganisms of apparent ages up to a few million years have previously been isolated and cultured. We find that the extent of aspartic acid racemization in permafrost cores increases very slowly up to an age of approximately 25,000 years (around 5 m depth). The apparent temperature of racemization over the age range 0-25,000 years, determined using measured aspartic acid racemization rate constants, is ?19 C. This apparent racemization temperature is significantly lower than the measured environmental temperature (?11 to ?13 C), and suggests active recycling of D-aspartic acid in Siberian permafrost up to an age of around 25,000 years. This indicates that permafrost organisms are capable of repairing some molecular damage incurred while they are in a ?dormant? state over geologic time.

  17. Amino acid racemization dating of Upper Pleistocene - Holocene terrestrial gastropods from a Mediterranean region (Murcia, SE Spain)

    NASA Astrophysics Data System (ADS)

    Garcia-Mayordomo, Julian; Ortiz, Jose E.; Torres, Trinidad; Insua-Arevalo, Juan M.; Martinez-Diaz, Jose J.; Altolaguirre, Yul; Canales-Fernandez, Maria L.; Martin-Banda, Raquel

    2014-05-01

    The amino acid racemization method has become a widely used geochronological tool for dating Quaternary deposits. The method is based on the fact that living organisms contain only L-amino acids which gradually racemize into D-amino acids after death. Thus, the D/L ratio increases with time after death until it is equal to 1, that is, when equilibrium is reached. Gastropod shells are particularly useful for amino acid racemization dating. Because the amino acid racemization method is not a numerical dating method in isolation, it needs to be calibrated, mainly with radiometric dating methods. The racemization process is genus- and temperature-dependent. In this work we present a preliminary analysis that compares the radiometric age estimated from different dating methods of a number of gastropods recovered in localities from Murcia (Southeastern Spain), with the age obtained through the amino acid racemization method. Taking advantage of recent paleoseismological research in the Murcia region (SE Spain), 28 gastropods specimens were collected from different trenches dug in young Quaternary alluvial deposits. The specimens were subsequently classified and then analyzed according to the standards protocols of the Biomolecular Stratigraphy Laboratory (UPM, Madrid School of Mines). The species found were Otala lactea, Iberus gualterianus, Sphincterochila candidissima and Theba pisana. The D/L ratios of aspartic acid, leucine, phenylalanine and glutamic acid were determined, and the corresponding average age of each specimen was calculated introducing the D/L values in the age calculation algorithm of Torres et al. (1997) for gastropods of central and southern Spain. The racemization age for each locality was then compared to the radiometric age of the deposit where the specimens were collected. To this respect, the samples were classified in different groups considering the reliability on the age control method. The most reliable sample consists only on dates obtained

  18. Reactivity of fluoride dentifrices with artificial caries. III. Quantitative aspects of acquired acid resistance (AAR): F uptake, retention, surface hardening and remineralization.

    PubMed

    White, D J

    1991-01-01

    A pH cycling remineralization/dimineralization model has been used to compare remineralization and acid resistance benefits provided by commercial MFP and NaF dentifrices. Test results show that fluoride dentifrice systems were effective in enhancing lesion remineralization and providing acquired acid resistance (AAR) to carious lesions, with AAR benefits considerably greater in magnitude. Fluoride uptake into the carious lesions was associated with remineralization and AAR benefits. Dentifrices containing the highest levels of soluble ionic fluoride were found most effective in this protocol with MFP dentifrices showing significantly less activity. MFP dentifrice efficacy was enhanced slightly in calcium abrasives. The enhanced activity could be explained by increased levels of background ionic fluoride in the formulations. In contrast to the latter effects, a dual-active NaF+MFP dentifrice in a calcium abrasive system exhibited decreased efficacy relative to a silica abrasive formulation due to incompatibility of free fluoride ion. Comparison of analytical techniques for measurement of AAR in shallow lesions demonstrates that surface microhardness methods match radiographic measures and are thus adequate for ICT measurement of cariogenicity and F remineralization. PMID:1812910

  19. Pharmacokinetics of (-)-folinic acid after oral and intravenous administration of the racemate.

    PubMed Central

    Greiner, P O; Zittoun, J; Marquet, J; Cheron, J M

    1989-01-01

    1. A pharmacokinetic study of the natural (-)-isomer of folinic acid ((-)-5 CHOTHF) and of total (-)-folates was performed in 12 healthy subjects after i.v. and oral administration of the racemic form of folinic acid. 2. After a 25 mg i.v. injection, (-)-5 CHOTHF kinetics were described by a biexponential function. The mean steady state volume of distribution (Vss) was 161; systemic and renal clearances averaged 335 and 53 ml min-1, respectively. After the same oral dose, (-)-5 CHOTHF was rapidly absorbed. Plasma concentrations of unchanged drug were much lower than those achieved after i.v. administration but in nine subjects, the disposition kinetics were also biexponential. Absolute bioavailability was only 4% as a consequence of a significant intestinal first pass effect. 3. AUC and t1/2Z values for total (-)-folates were similar after both routes of administration, indicating that the drug was fully absorbed. However the AUC of the active metabolite after i.v. dosage was only half that after oral dosage. 4. The amounts of total (-)-folates excreted in urine after both routes of administration were not significantly different and averaged one third of the dose after 24 h, whereas excretion of (-)-5 CHOTHF was three times less after oral treatment than after parenteral treatment. 5. Oral administration is a more suitable route for folinic acid therapy because more of the active metabolite is produced than after parenteral injection. PMID:2789922

  20. Enantioselective Crystallization of Sodium Chlorate in the Presence of Racemic Hydrophobic Amino Acids and Static Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Zorzano, María-Paz; Osuna-Esteban, Susana; Ruiz-Bermejo, Marta; Menor-Salván, Cesar; Veintemillas-Verdaguer, Sabino

    2014-06-01

    We study the bias induced by a weak (200 mT) external magnetic field on the preferred handedness of sodium chlorate crystals obtained by slow evaporation at ambient conditions of its saturated saline solution with 20 ppm of added racemic (dl) hydrophobic amino acids. By applying the Fisher test to pairs of experiments with opposing magnetic field orientation we conclude, with a confidence level of 99.7%, that at the water-air interface of this saline solution there is an enantioselective magnetic interaction that acts upon racemic mixtures of hydrophobic chiral amino acids. This interaction has been observed with the three tested racemic hydrophobic amino acids: dl-Phe, dl-Try and dl-Trp, at ambient conditions and in spite of the ubiquitous chiral organic contamination. This enantioselective magnetic dependence is not observed when there is only one handedness of added chiral amino-acid, if the added amino acid is not chiral or if there is no additive. This effect has been confirmed with a double blind test. This novel experimental observation may have implications for our view of plausible initial prebiotic scenarios and of the roles of the geomagnetic field in homochirality in the biosphere.

  1. A comparative study of the kinetics of amino acid racemization/epimerization in fossil and modern mollusk shells

    SciTech Connect

    Goodfriend, G.A. Carnegie Inst. of Washington, Washington DC ); Meyer, V.R. )

    1991-11-01

    The present study examines the question of whether heating experiments on modern shell material accurately model the pattern of kinetics of racemization/epimerization in fossils. Using one modern sample and four fossil samples (dating to 9700-1700 yr B.P.) of a species of land snail from the Negev Desert, the kinetic behavior of the samples in laboratory heating experiments are compared. Results are then compared to the Holocene trend in kinetic patterns observed in a large series of radio-carbon-dated shells. For most amino acids (alanine, alloisoleucine/isoleucine, phenylalanine, and glutamic acid), the fossil material displays the same pattern of kinetics in relation to time as the modern shells; deviant patterns are observed for aspartic acid, proline, and methionine. Adherence to a first order kinetic pattern in heated shells occurs only in alloisoleucine/isoleucine (within the range of D/L ratios studied). Differences in the temperature dependence of racemization/epimerization rates are found between modern and fossil samples. In most cases this relationship when extrapolated to natural temperatures, does not agree well with observed rates of racemization/epimerization in the fossil series. However the pattern of change in rate of racemization/epimerization with time in heating experiments generally follows the trend observed in the fossil series rather well. The experiments indicate that heating experiment results for certain amino acids, such as the widely used alloisoleucine/isoleucine, do give good predictions of kinetic patterns in relation to time in fossils but that predictions of the temperature dependence of rates are less accurate.

  2. Two types of rare earth-organic frameworks constructed by racemic tartaric acid

    SciTech Connect

    Jiang Zhanguo; Lv Yaokang; Cheng Jianwen; Feng Yunlong

    2012-01-15

    Hydrothermal reactions of rare earth oxides with racemic tartaric acid (H{sub 2}tar) yielded 7 rare earth(III) MOFs with general formulas [R{sub 2}(tar){sub 3}(H{sub 2}O){sub 2}]{sub n} (R=Y (1), Sm (4), Eu (5), Tb (6), Dy (7)) and [R{sub 2}(tar){sub 2}(C{sub 2}O{sub 4})(H{sub 2}O){sub 2}]{sub n}{center_dot}4nH{sub 2}O (R=La (2), Nd (3)). X-ray powder diffraction analysis and single-crystal X-ray diffraction analysis reveal that they present two different structural types. MOFs 1, 4, 5, 6 and 7 are isostructural and crystallize in the orthorhombic non-centrosymmetric space group Iba2, and feature unusual fsc-3,4-Iba2 topology. MOFs 2 and 3 are isostructural and crystallize in monoclinic P2{sub 1}/c space group and display rare fsx-4,5-P2{sub 1}/c topology containing hydrophilic channels bounded by triple helical chains along a axis. MOFs 3, 4, 5, 6 and 7 exhibit intense lanthanide characteristic photoluminescence at room temperature. - Graphical Abstract: [R{sub 2}(tar){sub 2}(C{sub 2}O{sub 4})(H{sub 2}O){sub 2}]{sub n}{center_dot}4nH{sub 2}O (R=La (2), Nd (3)) display rare fsx-4,5-P2{sub 1}/c topology containing hydrophilic channels bounded by triple helical chains along a axis. Highlights: Black-Right-Pointing-Pointer Two types of rare earth MOFs were synthesized by hydrothermal conditions. Black-Right-Pointing-Pointer MOFs feature unusual fsc-3,4-Iba2 and rare fsx-4,5-P2{sub 1}/c topology structures. Black-Right-Pointing-Pointer MOFs exhibit intense lanthanide characteristic photoluminescence.

  3. Immobilized chiral tropine ionic liquid on silica gel as adsorbent for separation of metal ions and racemic amino acids.

    PubMed

    Qian, Guofei; Song, Hang; Yao, Shun

    2016-01-15

    Tropine-type chiral ionic liquid with proline anion was immobilized on silica gel by chemical modification method for the first time, which was proved by elemental, infrared spectrum and thermogravimetric analysis. Secondly, the performance of this kind of ionic liquid-modified silica gel was investigated in the adsorption of some metal ions, which included Cu(2+), Fe(3+), Mn(2+) and Ni(2+). Then the effects of time, initial concentration and temperature on adsorption for Cu(2+) ions were studied in detail, which was followed by the further research of adsorption kinetics and thermodynamics. The adsorption could be better described by pseudo-second-order kinetics model and that the process was spontaneous, exothermic and entropy decreasing. In the mode of 'reuse after adsorption', the ionic liquid-modified silica gel with saturated adsorption of Cu(2+) was finally used in resolution of racemic amino acids for the first time. The static experiment showed that adsorption rate of two enantiomers was obviously different. Inspired by this, the complex was packed in chromatographic column for the separation of racemic amino acids and d-enantiomers were firstly eluted by water or ethanol. Steric hindrance was found as one of key influencing factors for its effect on the stability of the complex. PMID:26711153

  4. Phosphine-Catalyzed Doubly Stereoconvergent γ-Additions of Racemic Heterocycles to Racemic Allenoates: The Catalytic Enantioselective Synthesis of Protected α,α-Disubstituted α-Amino Acid Derivatives

    PubMed Central

    2015-01-01

    Methods have recently been developed for the phosphine-catalyzed asymmetric γ-addition of nucleophiles to readily available allenoates and alkynoates to generate useful α,β-unsaturated carbonyl compounds that bear a stereogenic center in either the γ or the δ position (but not both) with high stereoselectivity. The utility of this approach would be enhanced considerably if the stereochemistry at both termini of the new bond could be controlled effectively. In this report, we describe the achievement of this objective, specifically, that a chiral phosphepine can catalyze the stereoconvergent γ-addition of a racemic nucleophile to a racemic electrophile; through the choice of an appropriate heterocycle as the nucleophilic partner, this new method enables the synthesis of protected α,α-disubstituted α-amino acid derivatives in good yield, diastereoselectivity, and enantioselectivity. PMID:26192217

  5. Wide range of racemization of amino acids in peptides from human fossil bone and its implications for amino acid racemization dating

    SciTech Connect

    Kimber, R.W.L.; Hare, P.E. )

    1992-02-01

    Aspartic acid from an HCl hydrolyzed portion of 20-25th Dynasty Egyptian bone gave a D/L value of 0.28. Various peptide and molecular weight fractions separated before hydrolysis from another aliquot of the same bone portion yielded D/L aspartic acid values ranging from 0.09 to 0.68. Higher molecular weight and higher content of hydrophobic amino acids are factors leading to lower D/L aspartic acid values. Insoluble, high molecular weight polypeptide residues showed very low D/L aspartic acid values of 0.09. The authors propose that particularly stable peptides be isolated and characterized and then used for comparison with similarly isolated peptides from other fossil bone samples for purposes of age estimation.

  6. Numerical dating of a Late Quaternary spit-shoreline complex at the northern end of Silver Lake playa, Mojave Desert, California: A comparison of the applicability of radiocarbon, luminescence, terrestrial cosmogenic nuclide, electron spin resonance, U-series and amino acid racemization methods

    USGS Publications Warehouse

    Owen, L.A.; Bright, Jordon; Finkel, R.C.; Jaiswal, M.K.; Kaufman, D.S.; Mahan, S.; Radtke, U.; Schneider, J.S.; Sharp, W.; Singhvi, A.K.; Warren, C.N.

    2007-01-01

    A Late Quaternary spit-shoreline complex on the northern shore of Pleistocene Lake Mojave of southeastern California, USA was studied with the goal of comparing accelerator mass spectrometry (AMS) radiocarbon, luminescence, electron spin resonance (ESR), terrestrial cosmogenic radionuclide (TCN) surface exposure, amino acid racemization (AAR) and U-series dating methods. The pattern of ages obtained by the different methods illustrates the complexity of processes acting in the lakeshore environment and highlights the utility of a multi-method approach. TCN surface exposure ages (mostly ???20-30 ka) record the initial erosion of shoreline benches, whereas radiocarbon ages on shells (determined in this and previous studies) within the spit, supported by AAR data, record its construction at fluctuating lake levels from ???16 to 10 ka. Luminescence ages on spit sediment (???6-7 ka) and ESR ages on spit shells (???4 ka) are anomalously young relative to radiocarbon ages of shells within the same deposits. The significance of the surprisingly young luminescence ages is not clear. The younger ESR ages could be a consequence of post-mortem enrichment of U in the shells. High concentrations of detrital thorium in tufa coating spit gravels inhibited the use of single-sample U-series dating. Detailed comparisons such as this provide one of the few means of assessing the accuracy of Quaternary dating techniques. More such comparisons are needed. ?? 2007 Elsevier Ltd and INQUA.

  7. Importance of Hydrogen-Bonding Sites in the Chiral Recognition Mechanism Between Racemic D3 Terbium(III) Complexes and Amino Acids

    PubMed Central

    MOUSSA, AHMED; PHAM, CHRISTINE; BOMMIREDDY, SHRUTHI; MULLER, GILLES

    2009-01-01

    The perturbation of the racemic equilibrium of luminescent D3 terbium(III) complexes with chelidamic acid (CDA), a hydroxylated derivative of 2,6-pyridine-dicarboxylic acid (DPA), by added chiral biomolecules such as l-amino acids has been studied using circularly polarized luminescence and 13C NMR spectroscopy. It is shown in this work that the chiral-induced equilibrium shift of [Tb(CDA)3]6− by l-amino acids (i.e. l-proline or l-arginine) was largely influenced by the hydrogen-bonding networks formed between the ligand interface of racemic [Tb(CDA)3]6− and these added chiral agents. The capping of potential hydrogen-bonding sites by acetylation in l-proline led to a ∼100-fold drop in the induced optical activity of the [Tb(CDA)3]6−:N-acetyl-l-proline system. This result suggested that the hydrogen-bonding networks serve as the basis for further noncovalent discriminatory interactions between racemic [Tb(CDA)3]6− and added l-amino acids. PMID:18698640

  8. Racemic amino acids from the ultraviolet photolysis of interstellar ice analogues

    NASA Technical Reports Server (NTRS)

    Bernstein, Max P.; Dworkin, Jason P.; Sandford, Scott A.; Cooper, George W.; Allamandola, Louis J.

    2002-01-01

    The delivery of extraterrestrial organic molecules to Earth by meteorites may have been important for the origin and early evolution of life. Indigenous amino acids have been found in meteorites-over 70 in the Murchison meteorite alone. Although it has been generally accepted that the meteoritic amino acids formed in liquid water on a parent body, the water in the Murchison meteorite is depleted in deuterium relative to the indigenous organic acids. Moreover, the meteoritical evidence for an excess of laevo-rotatory amino acids is hard to understand in the context of liquid-water reactions on meteorite parent bodies. Here we report a laboratory demonstration that glycine, alanine and serine naturally form from ultraviolet photolysis of the analogues of icy interstellar grains. Such amino acids would naturally have a deuterium excess similar to that seen in interstellar molecular clouds, and the formation process could also result in enantiomeric excesses if the incident radiation is circularly polarized. These results suggest that at least some meteoritic amino acids are the result of interstellar photochemistry, rather than formation in liquid water on an early Solar System body.

  9. Temperature calibration of amino acid racemization: age implications for the Yuha skeleton

    USGS Publications Warehouse

    Bischoff, J.L.; Childers, W.M.

    1979-01-01

    D/L of aspartic acid ranged from 0.52 to 0.56 for femur samples of the Yuha skeleton. Subsurface temperature measurements made at the burial site indicate average annual temperature is 18??C and diagenetic temperature is 21.6??C. These data and a relation derived for the dependence of the aspartic acid rate constant on diagenetic temperature indicate an age of 23,600. The result is consistent with 14C and 230Th dating of calcrete found coating the bones. ?? 1979.

  10. NON-RACEMIC AMINO ACID PRODUCTION BY ULTRAVIOLET IRRADIATION OF ACHIRAL INTERSTELLAR ICE ANALOGS WITH CIRCULARLY POLARIZED LIGHT

    SciTech Connect

    De Marcellus, Pierre; Nuevo, Michel; Danger, Gregoire; Deboffle, Dominique; Le Sergeant d'Hendecourt, Louis; Meinert, Cornelia; Filippi, Jean-Jacques; Meierhenrich, Uwe J.; Nahon, Laurent E-mail: ldh@ias.u-psud.fr

    2011-02-01

    The delivery of organic matter to the primitive Earth via comets and meteorites has long been hypothesized to be an important source for prebiotic compounds such as amino acids or their chemical precursors that contributed to the development of prebiotic chemistry leading, on Earth, to the emergence of life. Photochemistry of inter/circumstellar ices around protostellar objects is a potential process leading to complex organic species, although difficult to establish from limited infrared observations only. Here we report the first abiotic cosmic ice simulation experiments that produce species with enantiomeric excesses (e.e.'s). Circularly polarized ultraviolet light (UV-CPL) from a synchrotron source induces asymmetric photochemistry on initially achiral inter/circumstellar ice analogs. Enantioselective multidimensional gas chromatography measurements show significant e.e.'s of up to 1.34% for ({sup 13}C)-alanine, for which the signs and absolute values are related to the helicity and number of CPL photons per deposited molecule. This result, directly comparable with some L excesses measured in meteorites, supports a scenario in which exogenous delivery of organics displaying a slight L excess, produced in an extraterrestrial environment by an asymmetric astrophysical process, is at the origin of biomolecular asymmetry on Earth. As a consequence, a fraction of the meteoritic organic material consisting of non-racemic compounds may well have been formed outside the solar system. Finally, following this hypothesis, we support the idea that the protosolar nebula has indeed been formed in a region of massive star formation, regions where UV-CPL of the same helicity is actually observed over large spatial areas.

  11. Aspartic Acid Racemization and Collagen Degradation Markers Reveal an Accumulation of Damage in Tendon Collagen That Is Enhanced with Aging*

    PubMed Central

    Thorpe, Chavaunne T.; Streeter, Ian; Pinchbeck, Gina L.; Goodship, Allen E.; Clegg, Peter D.; Birch, Helen L.

    2010-01-01

    Little is known about the rate at which protein turnover occurs in living tendon and whether the rate differs between tendons with different physiological roles. In this study, we have quantified the racemization of aspartic acid to calculate the age of the collagenous and non-collagenous components of the high strain injury-prone superficial digital flexor tendon (SDFT) and low strain rarely injured common digital extensor tendon (CDET) in a group of horses with a wide age range. In addition, the turnover of collagen was assessed indirectly by measuring the levels of collagen degradation markers (collagenase-generated neoepitope and cross-linked telopeptide of type I collagen). The fractional increase in d-Asp was similar (p = 0.7) in the SDFT (5.87 × 10−4/year) and CDET (5.82 × 10−4/year) tissue, and d/l-Asp ratios showed a good correlation with pentosidine levels. We calculated a mean (±S.E.) collagen half-life of 197.53 (±18.23) years for the SDFT, which increased significantly with horse age (p = 0.03) and was significantly (p < 0.001) higher than that for the CDET (34.03 (±3.39) years). Using similar calculations, the half-life of non-collagenous protein was 2.18 (±0.41) years in the SDFT and was significantly (p = 0.04) lower than the value of 3.51 (±0.51) years for the CDET. Collagen degradation markers were higher in the CDET and suggested an accumulation of partially degraded collagen within the matrix with aging in the SDFT. We propose that increased susceptibility to injury in older individuals results from an inability to remove partially degraded collagen from the matrix leading to reduced mechanical competence. PMID:20308077

  12. Enzymatic dynamic kinetic resolution of racemic N-formyl- and N-carbamoyl-amino acids using immobilized L-N-carbamoylase and N-succinyl-amino acid racemase.

    PubMed

    Soriano-Maldonado, Pablo; Las Heras-Vazquez, Francisco Javier; Clemente-Jimenez, Josefa María; Rodriguez-Vico, Felipe; Martínez-Rodríguez, Sergio

    2015-01-01

    Taking advantage of the catalytic promiscuity of L-carbamoylase from Geobacillus stearothermophilus CECT43 (BsLcar) and N-succinyl-amino acid racemase from Geobacillus kaustophilus CECT4264 (GkNSAAR), we have evaluated the production of different optically pure L-α-amino acids starting from different racemic N-formyl- and N-carbamoyl-amino acids using a dynamic kinetic resolution approach. The enzymes were immobilized on two different solid supports, resulting in improved stability of the enzymes in terms of thermostability and storage when compared to the enzymes in solution. The bienzymatic system retained up to 80% conversion efficiency after 20 weeks at 4 °C and up to 90% after 1 week at 45 °C. The immobilization process also resulted in a great enhancement of the activity of BsLcar toward N-formyl-tryptophan, showing for the first time that substrate specificity of L-carbamoylases can be influenced by this approach. The system was effective for the biosynthesis of natural and unnatural L-amino acids (enantiomeric excess (e.e.) >99.5%), such as L-methionine, L-alanine, L-tryptophan, L-homophenylalanine, L-aminobutyric acid, and L-norleucine, with a higher performance toward N-formyl-α-amino acid substrates. Biocatalyst reuse was studied, and after 10 reaction cycles, over 75% activity remained. PMID:24993356

  13. Polymorphic Crystallization and Crystalline Reorganization of Poly(l-lactic acid)/Poly(d-lactic acid) Racemic Mixture Influenced by Blending with Poly(vinylidene fluoride).

    PubMed

    Yu, Chengtao; Han, Lili; Bao, Jianna; Shan, Guorong; Bao, Yongzhong; Pan, Pengju

    2016-08-18

    The effects of poly(vinylidene fluoride) (PVDF) on the crystallization kinetics, competing formations of homocrystallites (HCs) and stereocomplexes (SCs), polymorphic crystalline structure, and HC-to-SC crystalline reorganization of the poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) racemic mixture were investigated. Even though the PLLA/PDLA/PVDF blends are immiscible, blending with PVDF enhances the crystallization rate and SC formation of PLLA/PDLA components at different temperatures that are higher or lower than the melting temperature of the PVDF component; it also facilitates the HC-to-SC melt reorganization upon heating. The crystallization rate and degree of SC crystallinity (Xc,SC) of PLLA/PDLA components in nonisothermal crystallization increase after immiscible blending with PVDF. At different isothermal crystallization temperatures, the crystallization half-time of PLLA/PDLA components decreases; its spherulitic growth rate and Xc,SC increase as the mass fraction of PVDF increases from 0 to 0.5 in the presence of either a solidified or a molten PVDF phase. The HCs formed in primary crystallization of PLLA/PDLA components melt and recrystallize into SCs upon heating; the HC-to-SC melt reorganization is promoted after blending with PVDF. We proposed that the PVDF-promoted crystallization, SC formation, and HC-to-SC melt reorganization of PLLA/PDLA components in PLLA/PDLA/PVDF blends stem from the enhanced diffusion ability of PLLA and PDLA chains. PMID:27414064

  14. Comparison of amino acid racemization geochronometry with lithostratigraphy, biostratigraphy, uranium-series coral dating, and magnetostratigraphy in the Atlantic Coastal Plain of the southeastern United States

    NASA Astrophysics Data System (ADS)

    McCartan, L.; Owens, J. P.; Blackwelder, B. W.; Szabo, B. J.; Belknap, D. F.; Kriausakul, N.; Mitterer, R. M.; Wehmiller, J. F.

    1982-11-01

    The results of an integrated study comprising litho- and biostratigraphic investigations, uranium-series coral dating, amino acid racemization in molluscs, and paleomagnetic measurements are compared to ascertain relative and absolute ages of Pleistocene deposits of the Atlantic Coastal Plain in North and South Carolina. Four depositional events are inferred for South Carolina and two for North Carolina by all methods. The data suggest that there are four Pleistocene units containing corals that have been dated at about 100,000 yr, 200,000 yr, 450,000 yr, and over 1,000,000 yr. Some conflicts exist between the different methods regarding the correlation of the younger of these depositional events between Charleston and Myrtle Beach. Lack of good uranium-series dates for the younger material at Myrtle Beach makes the correlation with the deposits at Charleston more difficult.

  15. Comparison of amino acid racemization geochronometry with lithostratigraphy, biostratigraphy, uranium-series coral dating, and magnetostratigraphy in the Atlantic Coastal Plain of the southeastern United States

    USGS Publications Warehouse

    McCartan, L.; Owens, J.P.; Blackwelder, B. W.; Szabo, B. J.; Belknap, D.F.; Kriausakul, N.; Mitterer, R.M.; Wehmiller, J. F.

    1982-01-01

    The results of an integrated study comprising litho- and biostratigraphic investigations, uranium-series coral dating, amino acid racemization in molluscs, and paleomagnetic measurements are compared to ascertain relative and absolute ages of Pleistocene deposits of the Atlantic Coastal Plain in North and South Carolina. Four depositional events are inferred for South Carolina and two for North Carolina by all methods. The data suggest that there are four Pleistocene units containing corals that have been dated at about 100,000 yr, 200,000 yr, 450,000 yr, and over 1,000,000 yr. Some conflicts exist between the different methods regarding the correlation of the younger of these depositional events between Charleston and Myrtle Beach. Lack of good uranium-series dates for the younger material at Myrtle Beach makes the correlation with the deposits at Charleston more difficult. ?? 1982.

  16. Some considerations regarding the use of amino acid racemization in human dentine as an indicator of age at death.

    PubMed

    Carolan, V A; Gardner, M L; Lucy, D; Pollard, A M

    1997-01-01

    An HPLC method is described for simultaneously obtaining the enantiomeric ratio of three amino acids (aspartic acid, serine, and glutamic acid) from dental collagen, with a view to using this information for estimating age at death. Results are reported from a sample of twenty three known age modern teeth, six known age 19th C. AD teeth, and two unknown age Romano-British teeth. It was found (as expected) that all three D/L ratios changed significantly with chronological age. Standard calibration techniques were used to estimate ages for the six 19th C. AD specimens from regression equations estimated from the modern specimens, and also to predict (for the first time) the error associated with such estimates. Errors using aspartic acid were found to be similar to those obtained by other methods of age estimation from dental evidence, serine, and glutamic acid providing much poorer age estimates. Additionally, a systematic difference in the age-enantiomeric ratio relationship was observed between modern and older dental samples. It is concluded that there is some fundamental difference in the observed enantiomeric ratios between modern teeth and older samples, possibly as a result of the chemical alteration of the dental proteins. PMID:8988569

  17. Liquid chromatographic resolution of amino acid esters of acyclovir including racemic valacyclovir on crown ether-based chiral stationary phases.

    PubMed

    Ahn, Seong Ae; Hyun, Myung Ho

    2015-03-01

    Valacyclovir, a potential prodrug for the treatment of patients with herpes simplex and herpes zoster, and its analogs were resolved on two chiral stationary phases (CSPs) based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 covalently bonded to silica gel. In order to find out an appropriate mobile phase condition, various mobile phases consisting of various organic modifiers in water containing various acidic modifiers were applied to the resolution of valacyclovir and its analogs. When 30% acetonitrile in water containing any of 0.05 M, 0.10 M, or 0.15 M perchloric acid was used as a mobile phase, valacyclovir and its analogs were resolved quite well on the two CSPs with the separation factors (α) in the range of 2.49 ~ 6.35 and resolutions (RS ) in the range of 2.95 ~ 12.21. Between the two CSPs, the CSP containing residual silanol protecting n-octyl groups on the silica surface was found to be better than the CSP containing residual silanol groups. PMID:25626672

  18. Enhanced catalysis and enantioselective resolution of racemic naproxen methyl ester by lipase encapsulated within iron oxide nanoparticles coated with calix[8]arene valeric acid complexes.

    PubMed

    Sayin, Serkan; Akoz, Enise; Yilmaz, Mustafa

    2014-09-14

    In this study, two types of nanoparticles have been used as additives for the encapsulation of Candida rugosa lipase via the sol-gel method. In one case, the nanoparticles were covalently linked with a new synthesized calix[8]arene octa valeric acid derivative (C[8]-C4-COOH) to produce new calix[8]arene-adorned magnetite nanoparticles (NP-C[8]-C4-COOH), and then NP-C[8]-C4-COOH was used as an additive in the sol-gel encapsulation process. In the other case, iron oxide nanoparticles were directly added into the sol-gel encapsulation process in order to interact electrostatically with both C[8]-C4-COOH and Candida rugosa lipase. The catalytic activities and enantioselectivities of two novel encapsulated lipases (Enc-NP-C[8]-C4-COOH and Enc-C[8]-C4-COOH@Fe3O4) in the hydrolysis reaction of racemic naproxen methyl ester were evaluated. The results showed that the activity and enantioselectivity of the lipase were improved when the lipase was encapsulated in the presence of calixarene-based additives. Indeed, the encapsulated lipases have an excellent rate of enantioselectivity, with E = 371 and 265, respectively, as compared to the free enzyme (E = 137). The lipases encapsulated with C[8]-C4-COOH and iron oxide nanoparticles (Enc-C[8]-C4-COOH@Fe3O4) retained more than 86% of their initial activities after 5 repeated uses and 92% with NP-C[8]-C4-COOH. PMID:25012138

  19. A regulatory cascade involving AarG, a putative sensor kinase, controls the expression of the 2'-N-acetyltransferase and an intrinsic multiple antibiotic resistance (Mar) response in Providencia stuartii.

    PubMed

    Rather, P N; Paradise, M R; Parojcic, M M; Patel, S

    1998-06-01

    A recessive mutation, aarG1, has been identified that resulted in an 18-fold increase in the expression of beta-galactosidase from an aac(2')-lacZ fusion. Transcriptional fusions and Northern blot analysis demonstrated that the aarG1 allele also resulted in a large increase in the expression of aarP, a gene encoding a transcriptional activator of aac(2')-Ia. The effects of aarG1 on aac(2')-Ia expression were mediated by aarP-dependent and -independent mechanisms. The aarG1 allele also resulted in a multiple antibiotic resistance (Mar) phenotype, which included increased chloramphenicol, tetracycline and fluoroquinolone resistance. This Mar phenotype also resulted from aarP-dependent and -independent mechanisms. Sequence analysis of the aarG locus revealed the presence of two open reading frames, designated aarR and aarG, organized in tandem. The putative AarR protein displayed 75% amino acid identity to the response regulator PhoP, and the AarG protein displayed 57% amino acid identity to the sensor kinase PhoQ. The aarG1 mutation, a C to T substitution, resulted in a threonine to isoleucine substitution at position 279 (T279I) in the putative sensor kinase. The AarG product was functionally similar to PhoQ, as it was able to restore wild-type levels of maganin resistance to a Salmonella typhimurium phoQ mutant. However, expression of the aarP and aac(2')-Ia genes was not significantly affected by the levels of Mg2+ or Ca2+, suggesting that aarG senses a signal other than divalent cations. PMID:9680222

  20. aarC, an essential gene involved in density-dependent regulation of the 2'-N-acetyltransferase in Providencia stuartii.

    PubMed Central

    Rather, P N; Solinsky, K A; Paradise, M R; Parojcic, M M

    1997-01-01

    The 2'-N-acetyltransferase [AAC(2')-Ia] in Providencia stuartii has a dual function where it is involved in the acetylation of peptidoglycan and certain aminoglycosides. A search for negative regulators of the aac(2')-Ia gene has resulted in the identification of aarC. A missense allele (aarC1) resulted in an 8.9-fold increase in beta-galactosidase accumulation from an aac(2')-lacZ transcriptional fusion. Northern blot analysis demonstrated an increase in aac(2')-Ia mRNA accumulation that was specific to cells at high density. In addition, the aarC1 allele also resulted in a substantial increase in the expression of aarP, a transcriptional activator of the aac(2')-Ia gene. The wild-type aarC gene was isolated by complementation and encodes a predicted protein of 365 amino acids with a molecular mass of 39,815 Da. The predicted AarC protein exhibited 88% amino acid homology to the previously identified GcpE protein of Escherichia coli and 86% homology to a gene product from Haemophilus influenzae. The E. coli gcpE gene was able to functionally complement the aarC1 allele in P. stuartii. The aarC1 allele was identified as a T to G transversion that resulted in a valine to glycine substitution at position 136 in the AarC protein. The aarC gene appears to be essential for cell viability as construction of a disrupted copy (aarC::lacZ) was possible only in cells that carried an episomal copy of aarC or gcpE. PMID:9079912

  1. Deuteration protects asparagine residues against racemization.

    PubMed

    Lowenson, Jonathan D; Shmanai, Vadim V; Shklyaruck, Denis; Clarke, Steven G; Shchepinov, Mikhail S

    2016-09-01

    Racemization in proteins and peptides at sites of L-asparaginyl and L-aspartyl residues contributes to their spontaneous degradation, especially in the biological aging process. Amino acid racemization involves deprotonation of the alpha carbon and replacement of the proton in the opposite stereoconfiguration; this reaction is much faster for aspartate/asparagine than for other amino acids because these residues form a succinimide ring in which resonance stabilizes the carbanion resulting from proton loss. To determine if the replacement of the hydrogen atom on the alpha carbon with a deuterium atom might decrease the rate of racemization and thus stabilize polypeptides, we synthesized a hexapeptide, VYPNGA, in which the three carbon-bound protons in the asparaginyl residue were replaced with deuterium atoms. Upon incubation of this peptide in pH 7.4 buffer at 37 °C, we found that the rate of deamidation via the succinimide intermediate was unchanged by the presence of the deuterium atoms. However, the accumulation of the D-aspartyl and D-isoaspartyl-forms resulting from racemization and hydrolysis of the succinimide was decreased more than five-fold in the deuterated peptide over a 20 day incubation at physiological temperature and pH. Additionally, we found that the succinimide intermediate arising from the degradation of the deuterated asparaginyl peptide was slightly less likely to open to the isoaspartyl configuration than was the protonated succinimide. These findings suggest that the kinetic isotope effect resulting from the presence of deuteriums in asparagine residues can limit the accumulation of at least some of the degradation products that arise as peptides and proteins age. PMID:27169868

  2. Synthesis of nano-sized stereoselective imprinted polymer by copolymerization of (S)-2-(acrylamido) propanoic acid and ethylene glycol dimethacrylate in the presence of racemic propranolol and copper ion.

    PubMed

    Alizadeh, Taher; Bagherzadeh, Azam; Shamkhali, Amir Nasser

    2016-06-01

    A new chiral functional monomer of (S)-2-(acrylamido) propanoic acid was obtained by reaction of (l)-alanine with acryloyl chloride. The resulting monomer was characterized by FT-IR and HNMR and then utilized for the preparation of chiral imprinted polymer (CIP). This was carried out by copolymerization of (l)-alanine-derived chiral monomer and ethylene glycol dimethacrylate, in the presence of racemic propranolol and copper nitrate, via precipitation polymerization technique, resulting in nano-sized networked polymer particles. The polymer obtained was characterized by scanning electron microscopy and FT-IR. The non-imprinted polymer was also synthesized and used as blank polymer. Density functional theory (DFT) was also employed to optimize the structures of two diasterometric ternary complexes, suspected to be created in the pre-polymerization step, by reaction of optically active isomers of propranolol, copper ion and (S)-2-(acrylamido) propanoic acid. Relative energies and other characteristics of the described complexes, calculated by the DFT, predicted the higher stability of (S)-propranolol involved complex, compared to (R)-propranolol participated complex. Practical batch extraction test which employed CIP as solid phase adsorbent, indicated that the CIP recognized selectively (S)-propranolol in the racemic mixture of propranolol; whereas, the non-imprinted polymer (NIP) showed no differentiation capability between two optically active isomers of propranolol. PMID:27040217

  3. IGFBP-1 hyperphosphorylation in response to leucine deprivation is mediated by the AAR pathway.

    PubMed

    Malkani, Niyati; Jansson, Thomas; Gupta, Madhulika B

    2015-09-01

    Insulin-like growth factor-1 (IGF-I) is the key regulator of fetal growth. IGF-I bioavailability is markedly diminished by IGF binding protein-1 (IGFBP-1) phosphorylation. Leucine deprivation strongly induces IGFBP-1 hyperphosphorylation, and plays an important role in fetal growth restriction (FGR). FGR is characterized by decreased amino acid availability, which activates the amino acid response (AAR) and inhibits the mechanistic target of rapamycin (mTOR) pathway. We investigated the role of AAR and mTOR in mediating IGFBP-1 secretion and phosphorylation in HepG2 cells in leucine deprivation. mTOR inhibition (rapamycin or raptor + rictor siRNA), or activation (DEPTOR siRNA) demonstrated a role of mTOR in leucine deprivation-induced IGFBP-1 secretion but not phosphorylation. When the AAR was blocked (U0126, or ERK/GCN2 siRNA), both IGFBP-1 secretion and hyperphosphorylation (pSer101/pSer119/pSer169) due to leucine deprivation were prevented. CK2 inhibition by TBB also attenuated IGFBP-1 phosphorylation in leucine deprivation. These results suggest that the AAR and mTOR independently regulate IGFBP-1 secretion and phosphorylation in response to decreased amino acid availability. PMID:25957086

  4. Dual Role of Hydrophobic Racemic Thioesters of α-Amino Acids in the Generation of Isotactic Peptides and Co-peptides in Water; Implications for the Origin of Homochirality

    NASA Astrophysics Data System (ADS)

    Illos, Roni A.; Clodic, Gilles; Bolbach, Gerard; Weissbuch, Isabelle; Lahav, Meir

    2010-02-01

    Thioesters of α-amino acids are considered as plausible monomers for the generation of the primeval peptides. DL-Leucine-thioethyl esters (LeuSEt), where the L-enantiomer was tagged with deuterium atoms, undergo polycondensation in water or in bicarbonate or imidazole buffer solutions to yield mainly heterochiral (atactic) peptides and diketopiperazine, as analyzed by MALDI-TOF and ESI mass-spectrometry. In variance, when polymerization of DL(d10) -Leu, first activated with N,N'-carbonyldiimidazole, then initiated with ethanethiol or with DL(d3) -LeuSEt yielded a library of peptides up to 30 detectable residues where those of homochiral sequence (isotactic) are the dominant diastereoisomers. At these conditions, racemic β-sheets are formed and operate as stereoselective templates in the process of chain-elongation. Isotopic L: L(d10)-Leu co-peptides were obtained in the polymerization of L(d10)-Leu with L-LeuSEt. By contrast, mixtures of oligo- D-Leu and oligo- L(d10)-Leu were obtained in the polymerization of mixtures of D-LeuSEt with activated L(d10)-Leu. Isotactic co-peptides containing Leu and Val residues were formed in the polymerization of mixtures of activated DL(d8)-Val with DL(d3) -LeuSEt in water, implying that the racemic β-sheets exert regio-enantio-selection but not chemo-selection. A reaction pathway is suggested, where LeuSEt operates both as initiator of the reaction as well as a multimer.

  5. Rationally re-designed mutation of NAD-independent l-lactate dehydrogenase: high optical resolution of racemic mandelic acid by the engineered Escherichia coli

    PubMed Central

    2012-01-01

    Background NAD-independent l-lactate dehydrogenase (l-iLDH) from Pseudomonas stutzeri SDM can potentially be used for the kinetic resolution of small aliphatic 2-hydroxycarboxylic acids. However, this enzyme showed rather low activity towards aromatic 2-hydroxycarboxylic acids. Results Val-108 of l-iLDH was changed to Ala by rationally site-directed mutagenesis. The l-iLDH mutant exhibited much higher activity than wide-type l-iLDH towards l-mandelate, an aromatic 2-hydroxycarboxylic acid. Using the engineered Escherichia coli expressing the mutant l-iLDH as a biocatalyst, 40 g·L-1 of dl-mandelic acid was converted to 20.1 g·L-1 of d-mandelic acid (enantiomeric purity higher than 99.5%) and 19.3 g·L-1 of benzoylformic acid. Conclusions A new biocatalyst with high catalytic efficiency toward an unnatural substrate was constructed by rationally re-design mutagenesis. Two building block intermediates (optically pure d-mandelic acid and benzoylformic acid) were efficiently produced by the one-pot biotransformation system. PMID:23176608

  6. Enantiomeric resolution of multiple chiral centres racemates by capillary electrophoresis.

    PubMed

    Ali, Imran; Suhail, Mohd; Al-Othman, Zeid A; Alwarthan, Abdulrahman; Aboul-Enein, Hassan Y

    2016-05-01

    Enantiomeric resolution of multichiral centre racemates is an important area as some multichiral centre racemates are of great medicinal importance. However, enantioseparation of such types of racemates is a challenging task. Amongst many analytical techniques, capillary electrophoresis is a powerful technique and may be used to resolve such racemates. Only few papers are available describing enantiomeric resolution of such racemates. Therefore, efforts have been made to describe the enantiomeric resolution of multichiral centre racemates by capillary electrophoresis. This article discusses the importance of multichiral racemates, the need for capillary electrophoresis in enantiomeric resolution and chiral resolution of multichiral centre racemates using various chiral selectors. Further, attempts have been made to discuss the future challenges and prospects of enantiomeric resolution of multichiral racemates. The various chiral selectors used for the purpose are chiral crown ether, cyclodextrins, polysaccharides, macrocyclic glycopeptide antibiotics and ligand exchange. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26840015

  7. Characterization and quantification of racemic and meso-ethylenediamine-N,N'-bis(2-hydroxy-5-sulfophenylacetic) acid/iron (III) by ion-pair ultra-high performance liquid chromatography coupled with diode array detector and electrospray tandem mass spectrometry.

    PubMed

    Biasone, Alessandro; Cianci, Giusto; Di Tommaso, Donata; Piaggesi, Alberto; Tagliavini, Emilio; Galletti, Paola; Moretti, Fabio

    2013-03-22

    EDDHSA/Fe is a promising substitute of EDDHA/Fe to fight iron chlorosis. o,o-EDDHSA structure contains two chiral carbons giving the racemic and meso couples of stereoisomers. Ion-pair HPLC and UHPLC-UV/Vis-ESI-MS/MS methods were developed for the determination of racemic and meso-o,o-EDDHSA/Fe in commercial samples of chelates. The lack of a commercial EDDHSA standard was overcome by sulfonation of a commercial available o,o-EDDHA standard and subsequent quantification by (1)H-NMR. Assignment of configurations was carried out starting from racemic and meso-o,o-EDDHA/Fe by direct sulfonation to give the corresponding o,o-EDDHSA/Fe isomers. The performances of these methods were assessed in terms of intra and inter-day precision, linearity and selectivity. The high selectivity and lower detection limit (nanomolar) of the UHPLC-ESI-MS/MS method could allow to deepen the knowledge relative to meso and rac-o,o-EDDHSA/Fe interactions with plants, its fate in different soil conditions, its mobility and other environmental aspects. PMID:23411145

  8. The Automated Aircraft Rework System (AARS): A system integration approach

    NASA Technical Reports Server (NTRS)

    Benoit, Michael J.

    1994-01-01

    The Mercer Engineering Research Center (MERC), under contract to the United States Air Force (USAF) since 1989, has been actively involved in providing the Warner Robins Air Logistics Center (WR-ALC) with a robotic workcell designed to perform rework automated defastening and hole location/transfer operations on F-15 wings. This paper describes the activities required to develop and implement this workcell, known as the Automated Aircraft Rework System (AARS). AARS is scheduled to be completely installed and in operation at WR-ALC by September 1994.

  9. Racemization of Isobornyl Chloride via Carbocations: A Nonclassical Look at a Classic Mechanism

    ERIC Educational Resources Information Center

    Rzepa, Henry S.; Allan, Charlotte S. M.

    2010-01-01

    Our understanding of carbonium ions as intermediates in chemical reaction mechanisms derives from the early work of Julius Stieglitz and the more famous Hans Meerwein, the latter studying the racemization of isobornyl chloride when treated with Lewis acids. This review analyzes how key mechanistic concepts for this reaction evolved and gives the…

  10. Spin crossover properties of enantiomers, co-enantiomers, racemates, and co-racemates.

    PubMed

    Qin, Long-Fang; Pang, Chun-Yan; Han, Wang-Kang; Zhang, Feng-Li; Tian, Lei; Gu, Zhi-Guo; Ren, Xuehong; Li, Zaijun

    2016-04-25

    Through multi-component self-assembly of chiral phenylethylamine, 1-alkyl-2-imidazolecarboxaldehyde and iron(ii) ions, two couples of enantiomeric iron(ii) complexes , , and with the formula of fac-Λ or Δ-[Fe(L)3](2+)(L = R or S-1-phenyl-N-(1-alkyl-1H-imidazol-2-ylmethylene)ethanamine) have been designed and synthesized as building blocks. Further binary cocrystallization of the prefabricated enantiomers enabled us to construct spin crossover co-enantiomers and , racemates and , and co-racemate . Compared with in a high spin state and with spin crossover at 291 K, the co-enantiomers exhibited gradual spin crossover at a higher temperature of 301 K, and the racemic alloys showed hysteresis loops induced by desolvation above room temperature. It was demonstrated that molecular chirality could be used effectively for stereochemical engineering of spin crossover materials. In addition, crystal packing, intramolecular π-π stacking, intermolecular C-Hπ interactions and solvent effects were elucidated to be responsible for the distinct spin crossover properties. This collective structural and magnetic study not only enriched the spin crossover library, but also provided a full comparison of optically pure, homochiral, and racemic materials with similar molecular structures. PMID:27021212

  11. Racemization of undesired enantiomers: Immobilization of mandelate racemase and application in a fixed bed reactor.

    PubMed

    Wrzosek, Katarzyna; Rivera, Mariel A García; Bettenbrock, Katja; Seidel-Morgenstern, Andreas

    2016-03-01

    Production of optically pure products can be based on simple unselective synthesis of racemic mixtures combined with a subsequent separation of the enantiomers; however, this approach suffers from a 50% yield limitation which can be overcome by racemization of the undesired enantiomer and recycling. Application of biocatalyst for the racemization steps offers an attractive option for high-yield manufacturing of commercially valuable compounds. Our work focuses on exploiting the potential of racemization with immobilized mandelate racemase. Immobilization of crude mandelate racemase via covalent attachment was optimized for two supports: Eupergit(®) CM and CNBr-activated Sepharose 4 Fast Flow. To allow coupling of enzymatic reaction with enantioselective chromatography, a mobile phase composition compatible with both processes was used in enzymatic reactor. Kinetic parameters obtained analyzing experiments carried out in a batch reactor could be successfully used to predict fixed-bed reactor performance. The applicability of the immobilized enzyme and the determined kinetic parameters were validated in transient experiments recording responses to pulse injections of R-mandelic acid. The approach investigated can be used for futher design and optimization of high yield combined resolution processes. The characterized fixed-bed enzymatic reactor can be integrated e.g. with chromatographic single- or multicolumn steps in various configurations. PMID:26773335

  12. Enantioselective enzymatic hydrolysis of racemic drugs by encapsulation in sol-gel magnetic sporopollenin.

    PubMed

    Yilmaz, Elif

    2012-05-01

    Candida rugosa lipase was encapsulated within a sol-gel procedure and improved considerably by fluoride-catalyzed hydrolysis of mixtures of octyltriethoxysilane and tetraethoxysilane in the presence of magnetic sporopollenin. The catalytic properties of the immobilized lipases were evaluated into model reactions, i.e., the hydrolysis of p-nitrophenylpalmitate (p-NPP), and the enantioselective hydrolysis of racemic naproxen methyl ester, mandelic acid methyl ester or 2-phenoxypropionic acid methyl ester that were studied in aqueous buffer solution/isooctane reaction system. The encapsulated magnetic sporopollenin (Spo-M-E) was found to give 319 U/g of support with 342% activity yield. It has been observed that the percent activity yields and enantioselectivity of the magnetic sporopollenin encapsulated lipase were higher than that of the encapsulated lipase without support. The substrate specificity of the encapsulated lipase revealed more efficient hydrolysis of the racemic naproxen methyl ester and 2-phenoxypropionic acid methyl ester than racemic mandelic acid methyl ester. It was observed that excellent enantioselectivity (E > 400) was obtained for encapsulated lipase with magnetic sporopollenin with an ee value of S-Naproxen and R-2 phenoxypropionic acid about 98%. PMID:21932062

  13. Racemization and the origin of optically active organic compounds in living organisms

    NASA Technical Reports Server (NTRS)

    Bada, J. L.; Miller, S. L.

    1987-01-01

    The organic compounds synthesized in prebiotic experiments are racemic mixtures. A number of proposals have been offered to explain how asymmetric organic compounds formed on the Earth before life arose, with the influence of chiral weak nuclear interactions being the most frequent proposal. This and other proposed asymmetric syntheses give only sight enantiomeric excess and any slight excess will be degraded by racemization. This applies particularly to amino acids where half-lives of 10(5)-10(6) years are to be expected at temperatures characteristic of the Earth's surface. Since the generation of chiral molecules could not have been a significant process under geological conditions, the origins of this asymmetry must have occurred at the time of the origin of life or shortly thereafter. It is possible that the compounds in the first living organisms were prochiral rather than chiral; this is unlikely for amino acids, but it is possible for the monomers of RNA-like molecules.

  14. Crystallization and biochemical characterization of the human spliceosomal Aar2-Prp8(RNaseH) complex.

    PubMed

    Santos, Karine; Preussner, Marco; Heroven, Anna Christina; Weber, Gert

    2015-11-01

    In eukaryotes, the removal of nuclear noncoding sequences (pre-mRNA splicing) is catalyzed by the spliceosome, which consists of five ribonucleoprotein particles (U1, U2, U4, U5 and U6 snRNPs, each with a respective snRNA) and a plethora of protein factors that aid spliceosomal maturation, assembly, activation and disassembly. Recently, the U5 snRNP maturation factor Aar2p from baker's yeast has been characterized structurally and biochemically. Aar2p binds to the RNaseH (RH) and Jab1/MPN domains of the highly conserved U5-specific Prp8p, which forms a framework for the spliceosomal catalytic centre. Thereby, Aar2p sterically excludes Brr2p, a helicase essential for the catalytic activation of the spliceosome, from Prp8p binding. At the same time, Aar2p blocks U4/U6 di-snRNA binding to Prp8p. Aar2p therefore prevents premature spliceosome activation and its functions are regulated by reversible phosphorylation. To date, little is known about the hypothetical human Aar2 (hsAar2) orthologue C20ORF4. This study identifies C20ORF4 (i) as part of the HeLa proteome by Western blotting and (ii) as a true Aar2 orthologue which binds to the RH domain (hsRH) of Prp8 and corroborates an evolutionary link between yeast and human Aar2 function. An elaborate strategy was devised to crystallize hsAar2 in complex with hsRH. The analysis of initial weakly diffracting crystals obtained by in situ proteolysis and homology modelling guided the design of an hsAar2 construct in which an internal loop was replaced by three serines (hsAar2(Δloop)). A complex of hsAar2(Δloop) and hsRH crystallized in space group C2; the crystals diffracted to 2.35 Å resolution and were suitable for structure determination by molecular-replacement approaches. The study presented here suggests a connection between Aar2 and the spliceosome in human cells and paves the way for structural studies of human Aar2. PMID:26527271

  15. FASD -- De Aar mums get beyond the 'tippling point'.

    PubMed

    Bateman, Chris

    2010-11-01

    When most of the low-income folk in the 'ghost train' town of De Aar began remonstrating with any pregnant mother who was boozing, excited campaigners thought they'd broken through the 'tippling point'. However, their research colleagues proved they'd gone even further -- the dedicated local platoon of social workers, nurses, therapists and volunteers had in three short years reduced the prevalence of fetal alcohol spectrum disorder (FASD) by 30%. This is in a town with the worst recorded FASD prevalence in any single community in the world, where 120 out of every 1 000 residents suffer from FASD (12%). PMID:21081033

  16. Racemic crystallography of synthetic protein enantiomers used to determine the X-ray structure of plectasin by direct methods

    PubMed Central

    Mandal, Kalyaneswar; Pentelute, Brad L; Tereshko, Valentina; Thammavongsa, Vilasak; Schneewind, Olaf; Kossiakoff, Anthony A; Kent, Stephen B H

    2009-01-01

    We describe the use of racemic crystallography to determine the X-ray structure of the natural product plectasin, a potent antimicrobial protein recently isolated from fungus. The protein enantiomers l-plectasin and d-plectasin were prepared by total chemical synthesis; interestingly, l-plectasin showed the expected antimicrobial activity, while d-plectasin was devoid of such activity. The mirror image proteins were then used for racemic crystallization. Synchrotron X-ray diffraction data were collected to atomic resolution from a racemic plectasin crystal; the racemate crystallized in the achiral centrosymmetric space group with one l-plectasin molecule and one d-plectasin molecule forming the unit cell. Dimer-like intermolecular interactions between the protein enantiomers were observed, which may account for the observed extremely low solvent content (13%–15%) and more highly ordered nature of the racemic crystals. The structure of the plectasin molecule was well defined for all 40 amino acids and was generally similar to the previously determined NMR structure, suggesting minimal impact of the crystal packing on the plectasin conformation. PMID:19472324

  17. Racemic crystallography of synthetic protein enantiomers used to determine the X-ray structure of plectasin by direct methods

    SciTech Connect

    Mandal, Kalyaneswar; Pentelute, Brad L.; Tereshko, Valentina; Thammavongsa, Vilasak; Schneewind, Olaf; Kossiakoff, Anthony A.; Kent, Stephen B.H.

    2009-06-30

    We describe the use of racemic crystallography to determine the X-ray structure of the natural product plectasin, a potent antimicrobial protein recently isolated from fungus. The protein enantiomers L-plectasin and D-plectasin were prepared by total chemical synthesis; interestingly, L-plectasin showed the expected antimicrobial activity, while D-plectasin was devoid of such activity. The mirror image proteins were then used for racemic crystallization. Synchrotron X-ray diffraction data were collected to atomic resolution from a racemic plectasin crystal; the racemate crystallized in the achiral centrosymmetric space group P1 with one L-plectasin molecule and one D-plectasin molecule forming the unit cell. Dimer-like intermolecular interactions between the protein enantiomers were observed, which may account for the observed extremely low solvent content (13%-15%) and more highly ordered nature of the racemic crystals. The structure of the plectasin molecule was well defined for all 40 amino acids and was generally similar to the previously determined NMR structure, suggesting minimal impact of the crystal packing on the plectasin conformation.

  18. Synthesis and Antifeedant Activity of Racemic and Optically Active Hydroxy Lactones with the p-Menthane System.

    PubMed

    Grudniewska, Aleksandra; Kłobucki, Marek; Dancewicz, Katarzyna; Szczepanik, Maryla; Gabryś, Beata; Wawrzeńczyk, Czesław

    2015-01-01

    Two racemic and two enantiomeric pairs of new δ-hydroxy-γ-lactones based on the p-menthane system were prepared from racemic and optically active cis- and trans-piperitols. The Johnson-Claisen rearrangement of the piperitols, epoxidation of the γδ-unsaturated esters, and acidic lactonization of the epoxy esters were described. The structures of the compounds were confirmed spectroscopically. The antifeedant activities of the hydroxy lactones and racemic piperitone were evaluated against three insect pests: lesser mealworm, Alphitobius diaperinus (Panzer); Colorado potato beetle, Leptinotarsa decemlineata (Say); and peach-potato aphid, Myzus persicae (Sulz.). The chemical transformation of piperitone by the introduction of a lactone moiety and a hydroxy group changed its antifeedant properties. Behavioral bioassays showed that the feeding deterrent activity depended on the insect species and the structure of the compounds. All hydroxy lactones deterred the settling of M. persicae. Among chewing insects, the highest sensitivity showed A. diaperinus adults. PMID:26132506

  19. Synthesis and Antifeedant Activity of Racemic and Optically Active Hydroxy Lactones with the p-Menthane System

    PubMed Central

    Grudniewska, Aleksandra; Kłobucki, Marek; Dancewicz, Katarzyna; Szczepanik, Maryla; Gabryś, Beata; Wawrzeńczyk, Czesław

    2015-01-01

    Two racemic and two enantiomeric pairs of new δ-hydroxy-γ-lactones based on the p-menthane system were prepared from racemic and optically active cis- and trans-piperitols. The Johnson-Claisen rearrangement of the piperitols, epoxidation of the γδ-unsaturated esters, and acidic lactonization of the epoxy esters were described. The structures of the compounds were confirmed spectroscopically. The antifeedant activities of the hydroxy lactones and racemic piperitone were evaluated against three insect pests: lesser mealworm, Alphitobius diaperinus (Panzer); Colorado potato beetle, Leptinotarsa decemlineata (Say); and peach-potato aphid, Myzus persicae (Sulz.). The chemical transformation of piperitone by the introduction of a lactone moiety and a hydroxy group changed its antifeedant properties. Behavioral bioassays showed that the feeding deterrent activity depended on the insect species and the structure of the compounds. All hydroxy lactones deterred the settling of M. persicae. Among chewing insects, the highest sensitivity showed A. diaperinus adults. PMID:26132506

  20. Localizing Perturbations of the Racemic Equilibria Involving Dipicolinate-Derived Lanthanide(III) Complexes.

    PubMed

    Nguyen, Brian T; Ingram, Andrew J; Muller, Gilles

    2016-04-01

    Helical D3 tris(4-amino-2,6-pyridine-dicarboxylate)terbium(III) and europium(III) complexes, which form a racemic equilibrium in aqueous solution, were prepared to study their secondary coordination sphere interactions with chiral amino acids. These interactions were probed using a combination of circularly polarized luminescence (CPL) and 13C NMR spectroscopy. The results indicate that, regardless of the interaction between the chiral molecule and the complex, without an accessible hydrogen-bond donor on the associating molecule, perturbation of the racemic equilibrium cannot occur. A generalized conclusion is established that indicates that the mechanism of chiral recognition by tris(dipicolinate)lanthanide(III) complexes is similar across a variety of analogous ligands. PMID:26935003

  1. Solubility properties of racemic praziquantel and its enantiomers.

    PubMed

    el-Arini, S K; Giron, D; Leuenberger, H

    1998-11-01

    The purpose of this study was to characterize the solubility and thermodynamic properties of the optical isomers of the anti-schistosomal drug, praziquantel (PZQ) and to compare these properties to those of the racemic product used in commercial preparations (Biltricide, generic drugs). The crystalline enantiomers of PZQ exhibited different thermal properties than the racemic drug. The melting points and the enthalpies of fusion obtained from the differential scanning calorimetry (DSC) scans were nearly identical between the isomers and were substantially lower than those of racemic PZQ [(+/-)-PZQ]. The DSC results indicate that (+/-)-PZQ is a racemic compound and not a racemic mixture. This was confirmed by powder x-ray diffraction analysis and the IR spectra. The 30 degrees decrease in the melting point was reflected in increased solubility of the enantiomers, which amounted to twice that of the racemic PZQ. The behavior of the isomers in the presence of beta-cyclodextrin (beta-CD) was studied in water at 37 degrees C. The solubility data (phase solubility diagrams) were linear for up to the highest concentration of added beta-CD investigated. The apparent stability constants determined from the phase solubility diagrams showed that both the (+) and (-) enantiomers as well as (+/-)-PZQ exhibited moderate affinity to form a 1:1 complex in solution with beta-CD. The findings of this study may be of importance when efforts are considered to improve pharmaceutical formulation of this anti-schistosomal drug. PMID:9834959

  2. The real gordian knot: racemic mixtures versus pure enantiomers.

    PubMed

    Szelenyi, I; Geisslinger, G; Polymeropoulos, E; Paul, W; Herbst, M; Brune, K

    1998-04-01

    Many drugs exist as asymmetric three-dimensional (chiral) molecules and will therefore have several stereoisomers. There are often pharmacodynamic, pharmacokinetic and/or toxicological differences between enantiomers. The choice between developing a racemate or single enantiomers depends on therapeutic advances and developmental costs involved. Regarding the target environment for drug intervention, even if natural physiological mediators are achiral, their receptors may demonstrate a preference for the (-)- or (+)-enantiomer of agonists or antagonists. It is also obvious that the majority of enzymes and channels are stereospecific, at least to a variable extent. From a pharmacokinetics point of view, chirality can have an influence on drug absorption, distribution, metabolism and elimination. With a few exceptions, toxicological differences between isomers of known drugs are less dramatic than thought to be and only seldom substantiate the necessity of a racemic switch. The pharmaceutical industry is currently very interested in the so-called "racemic switch." Before proceeding to a racemic switch it is necessary to determine if 1) it is chemically feasible to produce a single enantiomer; 2) a clinical advantage is obtainable through a racemic switch; and 3) a marketing advantage is obtainable. The real goal of a racemic switch should be the rational development of compounds that are profitable for the company and--first of all--beneficial for the patient. PMID:15616615

  3. Chiroptical properties and the racemization of pyrene and tetrathiafulvalene-substituted allene: substitution and solvent effects on racemization in tetrathiafulvalenylallene.

    PubMed

    Hasegawa, Masashi; Iwata, Seiya; Sone, Yasuto; Endo, Junta; Matsuzawa, Hideyo; Mazaki, Yasuhiro

    2014-01-01

    Dissymmetric 1,3-diphenylallene derivative 3 connected with 4,5-bis(methyl-thio)tetrathiafulvalenyl and 1-pyrenyl substituents was prepared and characterized. The molecular structure was determined by X-ray crystallographic analysis. Optical resolution was accomplished using a recycling chiral HPLC, and its chiroptical properties were examined with optical rotation and electronic circular dichroism (ECD) spectra. The title compound underwent photoracemization under daylight. This behavior was investigated in various solvents and compared with that of 1,3-bis(tetrathiafulvalenyl)allene (bis-TTF-allene) derivative 2. The first-order rate plot of the intensity of the ECD spectra at a given time interval gave the rate of racemization. Mild racemization was observed in polar solvents, whereas a relatively fast rate was obtained in less polar solvents. In addition, the TTF groups of the allene also accelerate the racemization rate. These results suggest that the racemization mechanism occurs via a non-polar diradical structure. PMID:24599123

  4. Adult Attachment Ratings (AAR): an item response theory analysis.

    PubMed

    Pilkonis, Paul A; Kim, Yookyung; Yu, Lan; Morse, Jennifer Q

    2014-01-01

    The Adult Attachment Ratings (AAR) include 3 scales for anxious, ambivalent attachment (excessive dependency, interpersonal ambivalence, and compulsive care-giving), 3 for avoidant attachment (rigid self-control, defensive separation, and emotional detachment), and 1 for secure attachment. The scales include items (ranging from 6-16 in their original form) scored by raters using a 3-point format (0 = absent, 1 = present, and 2 = strongly present) and summed to produce a total score. Item response theory (IRT) analyses were conducted with data from 414 participants recruited from psychiatric outpatient, medical, and community settings to identify the most informative items from each scale. The IRT results allowed us to shorten the scales to 5-item versions that are more precise and easier to rate because of their brevity. In general, the effective range of measurement for the scales was 0 to +2 SDs for each of the attachment constructs; that is, from average to high levels of attachment problems. Evidence for convergent and discriminant validity of the scales was investigated by comparing them with the Experiences of Close Relationships-Revised (ECR-R) scale and the Kobak Attachment Q-sort. The best consensus among self-reports on the ECR-R, informant ratings on the ECR-R, and expert judgments on the Q-sort and the AAR emerged for anxious, ambivalent attachment. Given the good psychometric characteristics of the scale for secure attachment, however, this measure alone might provide a simple alternative to more elaborate procedures for some measurement purposes. Conversion tables are provided for the 7 scales to facilitate transformation from raw scores to IRT-calibrated (theta) scores. PMID:24033268

  5. Antinociceptive activity of NK1 receptor antagonists: non-specific effects of racemic RP67580.

    PubMed Central

    Rupniak, N. M.; Boyce, S.; Williams, A. R.; Cook, G.; Longmore, J.; Seabrook, G. R.; Caeser, M.; Iversen, S. D.; Hill, R. G.

    1993-01-01

    1. Release of substance P in the dorsal horn is considered a primary event in the perception of pain. The profile of racemic RP67580, a non-peptide antagonist at the NK1 (substance P) receptor, was examined in a range of antinociception tests on rodents. 2. At doses up to 30 mg kg-1, s.c. racemic RP67580 exhibited antinociceptive activity in writhing and formalin paw tests in mice and gerbils. Acetic acid induced writhing and the licking response to formalin were reduced to 40-50% of the level observed in vehicle-treated animals (P < 0.05). However, this agent was not active in mouse tail flick, rat paw pressure or rat and guinea-pig formalin paw tests. 3. Like racemic RP67580, the calcium channel blockers nifedipine (30 mg kg-1, i.p.) and verapamil (10 or 20 mg kg-1, s.c.) inhibited the response to formalin by approximately 60% in gerbils (P < 0.05 compared with vehicle-treated animals). 4. Evidence for calcium channel antagonist activity of RP67580 was obtained in vitro. Racemic RP67580 inhibited calcium entry into depolarized strips of guinea-pig ileum longitudinal muscle myenteric plexus (apparent KB = 587 +/- 115 nM), inhibited [3H]-diltiazem binding to rabbit skeletal membranes (IC50 = 298 nM) and depressed high threshold calcium currents in neurones cultured from rat cortex (10% inhibition at 10 microM). 5. These findings indicate that the acute antinociceptive effects of RP67580 may not be attributable to a specific interaction with NK1 receptors and may be mediated via calcium channel blockade. PMID:8306108

  6. 76 FR 47612 - AAR Manufacturing, Inc.; Completion of Radiological Survey Activities at CSX Transportation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-05

    ... NRC informed AAR that radioactive thorium surface and subsurface contamination had been detected at... contamination on the CSXT property would result in doses well below NRC's criteria for unrestricted...

  7. Differential Occurrence of Interactions and Interaction Domains in Proteins Containing Homopolymeric Amino Acid Repeats.

    PubMed

    Pelassa, Ilaria; Fiumara, Ferdinando

    2015-01-01

    Homopolymeric amino acids repeats (AARs), which are widespread in proteomes, have often been viewed simply as spacers between protein domains, or even as "junk" sequences with no obvious function but with a potential to cause harm upon expansion as in genetic diseases associated with polyglutamine or polyalanine expansions, including Huntington disease and cleidocranial dysplasia. A growing body of evidence indicates however that at least some AARs can form organized, functional protein structures, and can regulate protein function. In particular, certain AARs can mediate protein-protein interactions, either through homotypic AAR-AAR contacts or through heterotypic contacts with other protein domains. It is still unclear however, whether AARs may have a generalized, proteome-wide role in shaping protein-protein interaction networks. Therefore, we have undertaken here a bioinformatics screening of the human proteome and interactome in search of quantitative evidence of such a role. We first identified the sets of proteins that contain repeats of any one of the 20 amino acids, as well as control sets of proteins chosen at random in the proteome. We then analyzed the connectivity between the proteins of the AAR-containing protein sets and we compared it with that observed in the corresponding control networks. We find evidence for different degrees of connectivity in the different AAR-containing protein networks. Indeed, networks of proteins containing polyglutamine, polyglutamate, polyproline, and other AARs show significantly increased levels of connectivity, whereas networks containing polyleucine and other hydrophobic repeats show lower degrees of connectivity. Furthermore, we observed that numerous protein-protein, -nucleic acid, and -lipid interaction domains are significantly enriched in specific AAR protein groups. These findings support the notion of a generalized, combinatorial role of AARs, together with conventional protein interaction domains, in shaping

  8. Stereoselective sulphate conjugation of racemic terbutaline by human liver cytosol.

    PubMed

    Walle, T; Walle, U K

    1990-07-01

    1. The enantioselectivity of the sulphation of racemic terbutaline by phenolsulphotransferases was examined in vitro using cytosol from human livers (n = 3) and [35S]-3'-phosphoadenosine-5'-phosphosulphate (PAP35S) as the sulphate donor. 2. The radioactive sulphate conjugate formed was isolated by h.p.l.c. and its enantiomers were separated intact by h.p.l.c. after chiral derivatization. 3. Sulphation of racemic terbutaline occurred with the same apparent Km value for both enantiomers (270 microM). The extent of sulphation of the (+)-enantiomer was double that of the (-)-enantiomer, solely due to a difference in their apparent Vmax values. 4. Sulphation of racemic prenalterol, a structural analogue of terbutaline, also showed a two-fold preference for the (+)-enantiomer. 5. These findings suggest that enantioselective sulphate conjugation of chiral phenolic sympathomimetic amine drugs may lead to enantioselective pharmacokinetics that should be considered in the clinical use of these drugs. PMID:2390423

  9. The cost effectiveness of levalbuterol versus racemic albuterol.

    PubMed

    Quinn, Campion

    2004-07-01

    Albuterol is a selective beta2-agonist that is widely used in the prevention and treatment of reactive airway disease. It is formulated as a racemic mixture containing equal parts of the R- and S-isomers. The therapeutic activity of albuterol is due entirely to the R-isomer, whereas the S-isomer may actually have detrimental effects. Because the slowly metabolized S-isomer tends to accumulate in the body, there has been concern that chronic use of racemic albuterol might lead to loss of effectiveness and clinical deterioration, with potentially serious health and cost consequences. Levalbuterol is a formulation containing only the R-isomer of albuterol, and clinical trials have demonstrated that it offers therapeutic advantages over racemic albuterol. The cost effectiveness of levalbuterol derives mainly from reduced need for acute medical care and hospitalization. PMID:15354680

  10. Induced circularly polarized luminescence arising from anion or protein binding to racemic emissive lanthanide complexes

    NASA Astrophysics Data System (ADS)

    Carr, Rachel; Puckrin, Robert; McMahon, Brian K.; Pal, Robert; Parker, David; Pålsson, Lars-Olof

    2014-06-01

    A circularly polarized luminescence (CPL) spectrometer has been built and used to study the binding interaction of lactate and four different proteins with racemic EuIII and TbIII complexes in aqueous solution. Lactate binding gives rise to strong induced CPL spectra, and the observed emission dissymmetry factors vary linearly with enantiomeric composition. Particularly strong induced TbIII CPL also characterizes the binding interaction of alpha-1-acid glycoprotein with a dissociation constant, Kd, of 2.5 μM.

  11. Diversity in a simple co-crystal: racemic and kryptoracemic behaviour.

    PubMed

    Rao Khandavilli, U B; Lusi, Matteo; Bhogala, Balakrishna R; Maguire, Anita R; Stein, Matthias; Lawrence, Simon E

    2016-07-01

    The crystal structure containing (±)-3-methyl-2-phenylbutyramide with salicylic acid is the first example of a kryptoracemate co-crystal. It exhibits the first temperature mediated reversible single-crystal to single-crystal transition between two kryptoracemate forms, in addition to crystallising in another, racemic, form. Theoretical calculations and structural analysis reveal that there are only small differences in both energy and packing arrangements between the three forms. These results suggest that co-crystals can be an opportunity to investigate kryptoracemate behaviour. PMID:27297725

  12. Which bioequivalence study for a racemic drug? Application to milnacipran.

    PubMed

    Deprez, D; Chassard, D; Baille, P; Mignot, A; Ung, H L; Puozzo, C

    1998-01-01

    Milnacipran, a new non tricyclic antidepressant drug, is a racemic mixture (F2207) composed of two enantiomers: F2695 and F2696, both demonstrated to be active. A randomized open label, single-dose latin square study was undertaken in 24 healthy volunteers to compare, based on racemate data, the relative bioavailability of two new formulations to that of a reference formulation. Later on, as suggested by actual regulatory trend, analysis was carried out on enantiomer data, although in a supportive way. Bioequivalence was assessed on calculation of 90% confidence intervals for log-transformed Cmax and AUC(0-infinity) and on Wilcoxon test for Tmax with a 5% level of significance. Based on racemate data, both test formulations were demonstrated to be equivalent to the reference capsule in terms of Cmax and AUC-(0-infinity). Differences in Tmax reached statistical significance, although their mean magnitude was small, and probably not relevant when related to antidepressant long-term therapy. When considering the test capsule - reference capsule comparison, the equivalence demonstrated for the racemate reflect that of each enantiomer. On the contrary, equivalence between the test tablet and the reference capsule demonstrated for the racemate, is not supported by both enantiomers as Cmax of F2696 fails to reach bioequivalence criteria, making more uncertain the conclusion of bioequivalence. From this experience, it seems than when equivalence is demonstrated close to the limits for the racemate, it is difficult, especially for a low variability drug such as milnacipran, to comply with equivalence criteria for both enantiomers. PMID:9725476

  13. Protein L-isoaspartyl methyltransferase catalyzes in vivo racemization of Aspartate-25 in mammalian histone H2B.

    PubMed

    Young, Glen W; Hoofring, Sarah A; Mamula, Mark J; Doyle, Hester A; Bunick, Gerard J; Hu, Yonglin; Aswad, Dana W

    2005-07-15

    Protein L-isoaspartyl methyltransferase (PIMT) has been implicated in the repair or metabolism of proteins containing atypical L-isoaspartyl peptide bonds. The repair hypothesis is supported by previous studies demonstrating in vitro repair of isoaspartyl peptides via formation of a succinimide intermediate. Utilization of this mechanism in vivo predicts that PIMT modification sites should exhibit significant racemization as a side reaction to the main repair pathway. We therefore studied the D/L ratio of aspartic acid at specific sites in histone H2B, a known target of PIMT in vivo. Using H2B from canine brain, we found that Asp25 (the major PIMT target site in H2B) was significantly racemized, exhibiting d/l ratios as high as 0.12, whereas Asp51, a comparison site, exhibited negligible racemization (D/L < or = 0.01). Racemization of Asp25 was independent of animal age over the range of 2-15 years. Using H2B from 2-3-week mouse brain, we found a similar D/L ratio (0.14) at Asp25 in wild type mice, but substantially less racemization (D/L = 0.035) at Asp25 in PIMT-deficient mice. These findings suggest that PIMT functions in the repair, rather than the metabolic turnover, of isoaspartyl proteins in vivo. Because PIMT has numerous substrates in cells, these findings also suggest that D-aspartate may be more common in cellular proteins than hitherto imagined and that its occurrence, in some proteins at least, is independent of animal age. PMID:15908425

  14. Application of direct crystallization for racemic compound propranolol hydrochloride.

    PubMed

    Wang, Xiujuan; Lu, Jie; Ching, Chi Bun

    2007-10-01

    The application of direct crystallization integrating with chromatography to the resolution of a racemic compound propranolol hydrochloride was studied and the crystallization progression was clearly illustrated in terms of the diagram of solubility and metastable zone widths with different enantiomeric compositions. The solubility and metastable zone widths of propranolol hydrochloride in the mixture of methanol and isopropanol were determined using an in situ Lasentec Focused Beam Reflectance Measurement (FBRM) probe. The direct crystallizations were carried out in an automatic lab reactor (Mettler Toledo LabMax) system. The optical purity of final product crystals was examined using differential scanning calorimetry (DSC), HPLC and PXRD. The crystal size distribution and morphology were analyzed using Malvern Mastersizer and Jeol SEM. It was found that optically pure crystal product could be obtained within certain safe supersaturation limit and there was no evidence of polymorph or solvate/hydrate transformation during the crystallization process. There was no selectivity of crystal growth or nucleation between the pure enantiomer and its racemate when the solution reaches the temperature lower than saturation temperature of the racemate. Hence, the critical supersaturation control of a solution was essential to obtain pure enantiomers from a partially resolved racemate. PMID:17549769

  15. Cysteine Racemization on IgG Heavy and Light Chains

    PubMed Central

    Zhang, Qingchun; Flynn, Gregory C.

    2013-01-01

    Under basic pH conditions, the heavy chain 220-light chain 214 (H220-L214) disulfide bond, found in the flexible hinge region of an IgG1, can convert to a thioether. Similar conditions also result in racemization of the H220 cysteine. Here, we report that racemization occurs on both H220 and L214 on an IgG1 with a λ light chain (IgG1λ) but almost entirely on H220 of an IgGl with a κ light chain (IgG1κ) under similar conditions. Likewise, racemization was detected at significant levels on H220 and L214 on endogenous human IgG1λ but only at the H220 position on IgG1κ. Low but measurable levels of d-cysteines were found on IgG2 cysteines in the hinge region, both with monoclonal antibodies incubated under basic pH conditions and on antibodies isolated from human serum. A simplified reaction mechanism involving reversible β-elimination on the cysteine is presented that accounts for both base-catalyzed racemization and thioether formation at the hinge disulfide. PMID:24142697

  16. Determination of relative enantiomer migration order using a racemic sample.

    PubMed

    Müllerová, Ludmila; Dubský, Pavel; Ördögová, Magda; Gaš, Bohuslav

    2015-12-11

    We developed a method that enables us to distinguish between the same or the opposite enantiomer migration order (EMO) of two enantiomers of a chiral compound with two different selectors. The method is applicable to racemic samples and thus a standard of the pure enantiomeric form(s) is not required. First, complexation constants and mobilities of complexes of the two enantiomers with the first and second selector are determined. However, for a racemic sample it is not possible to deduce whether the first migrating enantiomer with one selector is the same one as the first migrating enantiomer with the second selector. A specific mixture of the two selectors is designed to resolve this. In case the two enantiomers exhibit the same, respectively the opposite EMO in the two selectors, the mixture does, respectively does not separate the racemic sample. Thus two peaks are detected in the first case, while a single coalescent peak is recorded in the opposite case. We demonstrate the method on a racemic sample of amphetamine. Its relative EMO is determined with three cyclodextrins, heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, (2-hydroxypropyl)-β-cyclodextrin and heptakis(2,3-di-O-acetyl-6-O-sulfo)-β-cyclodextrin. PMID:26585204

  17. Oxyma-based phosphates for racemization-free peptide segment couplings

    PubMed Central

    Mitachi, Katsuhiko; Kurosu, Yuki E.; Hazlett, Brandon T.; Kurosu, Michio

    2016-01-01

    Glyceroacetonide-Oxyma [(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 2-cyano-2-(hydroxyimino)acetate (1)] displayed remarkable physico-chemical properties as an additive for peptide-forming reactions. Although racemization-free amide-forming reactions have been established for N-urethane-protected α-amino acids with EDCI, 1, and NaHCO3 in water or DMF-water media, amide-forming reactions of N-acyl-protected α-amino acids and segment couplings of oligopeptides still require further development. Diethylphosphoryl-Glyceroacetonide-Oxyma (DPGOx, 3) exhibits relative stability in aprotic solvents and is an effective coupling reagent for N-acyl-protected α-amino acids and oligo peptide segments. The conditions reported here is also effective in lactam-forming reactions. Unlike most of the reported coupling reagents, simple aqueous work-up procedures can remove the reagent and by-products generated in the reactions. PMID:26856693

  18. Homochiral oligopeptides via surface recognition and enantiomeric cross impediment in the polymerization of racemic phenylalanine N-carboxyanhydride crystals suspended in water.

    PubMed

    Nery, Jose Geraldo; Eliash, Ran; Bolbach, Gerard; Weissbuch, Isabelle; Lahav, Meir

    2007-08-01

    As part of our program on the search of possible prebiotic routes for the formation of oligopeptides of homochiral sequence (isotactic) from racemic precursors in aqueous environment, we report the polymerization of racemic crystals of phenylalanine N-carboxyanhydrides, enantioselectively tagged with five deuterium atoms, suspended in water containing various amine initiators. Racemic mixtures of isotactic oligopeptides, comprising up to 25 repeat units of the same handedness, as the dominant component for each length, were observed in a MALDI-TOF mass spectrometry analysis. The racemic mixtures of the peptides could be desymmetrized by initiating the polymerization reaction with water-soluble methyl esters of either enantiopure alpha-amino acids or dipeptides. A three-step mechanism is proposed to account for these results: (i) Surface recognition of the chiral initiator by the chiral sites present at specific faces of the crystal; (ii) Oligopeptide elongation at the polymer/crystal interface; and (iii) Self-assembly of the short isotactic peptides into racemic antiparallel beta-sheets as templates followed by cross-enantiomeric impediment in the growth of enantiomeric chains at the peptide beta-sheet/crystal interface. PMID:17354263

  19. Long-term management of AAR-affected structures - An international perspective

    SciTech Connect

    Charlwood, R.G.; Solymar, Z.V.

    1995-12-31

    The objective of the paper is to review international practice and comment on progress made in the long-term management of existing AAR-affected dams and hydroelectric plants. A updated detailed worldwide listing which now includes 104 AAR-affected structures constructed since 1900 will be presented. The listing gives summary data on the year of construction, the year that significant problems were noted, aggregate and cement types, measured expansion rates, test data, time to initial deterioration, duration of reaction, damage to the structures and effects on equipment, and repairs or replacement. A comprehensive bibliography will also be given. Analysis of the database and significant case histories will be used to identify issues affecting dam safety, plant operations, remedial measures and long-term performance of AAR-affected structures. The presentation will be illustrated by several case histories where remedial measures have been implemented.

  20. Copper-catalyzed divergent kinetic resolution of racemic allylic substrates.

    PubMed

    Pineschi, Mauro; Di Bussolo, Valeria; Crotti, Paolo

    2011-10-01

    When a racemic mixture is fully consumed the products may still be enantiomerically enriched. In particular, the regiodivergent kinetic resolution is a process in which a single chiral catalyst or reagent reacts with a racemic substrate to form regioisomers possessing an opposite configuration on the newly-formed stereogenic centers. This review reports the major advances in the field of the copper-catalyzed regiodivergent and stereodivergent kinetic resolution of allylic substrates with organometallic reagents. The chiral recognition matching phenomena found with particular allylic substrates with the absolute configuration of the chiral catalyst allows in some cases an excellent control of the regio- and stereoselectivity, sheding some light on the so-called "black-box" mechanism of a copper-catalyzed asymmetric allylic alkylation. PMID:21837639

  1. Hidden chirality in superficially racemic patchy silver films.

    PubMed

    Larsen, George K; He, Yizhuo; Ingram, Whitney; Zhao, Yiping

    2013-01-01

    Chiral patchy particle films where morphological enantiomers exist in equal proportion are found to have significant circular dichroism. It is determined that the rotation direction during glancing angle deposition breaks the racemic symmetry, resulting in a distribution of material which enhances the chirality of one set of enantiomers relative to the other. Microscopic analysis and geometric chirality calculations reveal that the chirality of the bulk film results from incomplete cancellations of even stronger local chiralities. PMID:24256449

  2. Enantioselectivity of hydroxylation of racemic piperitone by fungi.

    PubMed

    Grudniewska, Aleksandra; Gniłka, Radosław; Wawrzeńczyk, Czesław

    2010-11-01

    The biotransformation of racemic piperitone ((±)-1) was investigated using four strains of fungi selected in the screening procedure. The substrate was transformed by Botrytis cinerea AM235, Absidia cylindrospora AM336, Absidia coerulea AM93, and Absidia glauca AM177 into more polar metabolites. The transformation of racemic piperitone ((±)-1) catalyzed by B. cinerea AM235 gave 7-hydroxypiperitone (2) as the only product. The biotransformation of (±)-1 by A. cylindrospora AM336 afforded mixture of three products: (-)-(R)-7-hydroxypiperitone ((-)-2), (+)-(4S,6R)-trans-6-hydroxypiperitone ((+)-3), and (+)-(4R,6R)-cis-6-hydroxypiperitone ((+)-4). The transformation of this substrate ((±)-1) by A. coerulea AM93 gave (±)-7-hydroxypiperitone ((±)-2), (-)-(4R,6S)-trans-6-hydroxypiperitone (-)-3), and (-)-(4S,6S)-cis-6-hydroxypiperitone ((-)-4). The last strain studied, A. glauca AM177, converted racemic piperitone ((±)-1) to four products: (+)-(S)-7-hydroxypiperitone (2), (+)-(4S,6R)-trans-6-hydroxypiperitone ((+)-3), (±)-cis-6-hydroxypiperitone ((±)-4), and 8-hydroxypiperitone (5). PMID:20872669

  3. Scalemic and racemic imprinting with a chiral crosslinker.

    PubMed

    Hebert, Britney; Meador, Danielle S; Spivak, David A

    2015-08-26

    The development of molecularly imprinted chiral stationary phases has traditionally been limited by the need for a chiral pure template. Paradoxically, availability of a chiral pure template largely defeats the purpose of developing a chiral stationary phase. To solve this paradox, imprinting of scalemic and racemic template mixtures was investigated using both chiral (N-α-bismethacryloyl-L-alanine) and achiral (N,O-bisacrylamide ethanolamine) crosslinkers. Imprinting of scalemic mixtures provided polymers capable of partial separation of Boc-tyrosine enantiomers with virtually the same results when using either the chiral or achiral crosslinker. However, the chiral crosslinker was required for chiral differentiation by the racemic imprinted polymers which were evaluated in both batch rebinding and chromatographic modes. Batch rebinding analysis revealed intersecting binding isotherms for the L- and D-Boc-tyrosine, indicating bias for the D or L enantiomer is concentration dependent. Partial chromatographic separation was achieved by the racemic imprinted polymers providing variable D or L bias in equal probability over multiple replicates of polymer synthesis. Correlation of enantiomer bias with the batch rebinding results and optimization of HPLC parameters are discussed. PMID:26347178

  4. Enzymatic kinetic resolution of racemic ibuprofen: past, present and future.

    PubMed

    José, Carla; Toledo, María Victoria; Briand, Laura E

    2016-10-01

    This review is a journey concerning the investigations of the kinetic resolution of racemic ibuprofen for the last 20 years. The relevancy of the pharmacological uses of the S( + ) enantiomer along with its higher cost compared with racemic profen are the driving forces of a variety of scientific research studies addressing the enzymatic resolution of ibuprofen through enantiomeric esterification using lipases as biocatalysts. Lipases of fungal sources such as Candida rugosa, Rhizomucor miehei and the lipase B of Candida antarctica have been extensively studied both in homogeneous and heterogeneous (immobilized on solid supports) processes. In this context, the various alcohols and organic co-solvents frequently used in the esterification of racemic ibuprofen are summarized and discussed in this review. Moreover, recent investigations using membranes as reactors coupled with the separation of the desired product and microfluidic devices are presented. Finally, some guidelines about future perspectives regarding the technology of the kinetic resolution of profens and research niches are given. PMID:26121932

  5. Aqueous microwave-assisted solid-phase peptide synthesis using Fmoc strategy. III: racemization studies and water-based synthesis of histidine-containing peptides.

    PubMed

    Hojo, Keiko; Shinozaki, Natsuki; Hidaka, Koushi; Tsuda, Yuko; Fukumori, Yoshinobu; Ichikawa, Hideki; Wade, John D

    2014-10-01

    In this study, we describe the first aqueous microwave-assisted synthesis of histidine-containing peptides in high purity and with low racemization. We have previously shown the effectiveness of our synthesis methodology for peptides including difficult sequences using water-dispersible 9-fluorenylmethoxycarbonyl-amino acid nanoparticles. It is an organic solvent-free, environmentally friendly method for chemical peptide synthesis. Here, we studied the racemization of histidine during an aqueous-based coupling reaction with microwave irradiation. Under our microwave-assisted protocol using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, the coupling reaction can be efficiently performed with low levels of racemization of histidine. Application of this water-based microwave-assisted protocol with water-dispersible 9-fluorenylmethoxycarbonyl-amino acid nanoparticles led to the successful synthesis of the histidine-containing hexapeptide neuropeptide W-30 (10-15), Tyr-His-Thr-Val-Gly-Arg-NH₂, in high yield and with greatly reduced histidine racemization. PMID:24965528

  6. Comparison of racemic epi-inosose and (-)-epi-inosose.

    PubMed

    Krishnaswamy, Shobhana; Patil, Madhuri T; Shashidhar, Mysore S

    2011-11-01

    The conversion of myo-inositol to epi-inositol can be achieved by the hydride reduction of an intermediate epi-inosose derived from myo-inositol. (-)-epi-Inosose, (I), crystallized in the monoclinic space group P2(1), with two independent molecules in the asymmetric unit [Hosomi et al. (2000). Acta Cryst. C56, e584-e585]. On the other hand, (2RS,3SR,5SR,6SR)-epi-inosose, C(6)H(10)O(6), (II), crystallized in the orthorhombic space group Pca2(1). Interestingly, the conformation of the molecules in the two structures is nearly the same, the only difference being the orientation of the C-3 and C-4 hydroxy H atoms. As a result, the molecular organization achieved mainly through strong O-H···O hydrogen bonding in the racemic and homochiral lattices is similar. The compound also follows Wallach's rule, in that the racemic crystals are denser than the optically active form. PMID:22051958

  7. Separation and enrichment of enantiopure from racemic compounds using magnetic levitation.

    PubMed

    Yang, Xiaochuan; Wong, Shin Yee; Bwambok, David K; Atkinson, Manza B J; Zhang, Xi; Whitesides, George M; Myerson, Allan S

    2014-07-18

    Crystallization of a solution with high enantiomeric excess can generate a mixture of crystals of the desired enantiomer and the racemic compound. Using a mixture of S-/RS-ibuprofen crystals as a model, we demonstrated that magnetic levitation (MagLev) is a useful technique for analysis, separation and enantioenrichment of chiral/racemic products. PMID:24875274

  8. Aqueous microwave-assisted solid-phase peptide synthesis using fmoc strategy. II. Racemization studies and water based synthesis of cysteine-containing peptides.

    PubMed

    Hojo, Keiko; Shinozaki, Natsuki; Hara, Asaki; Onishi, Mare; Fukumori, Yoshinobu; Ichikawa, Hideki

    2013-10-01

    We have developed a microwave (MW)-assisted peptide synthesis using Fmoc-amino acid nanoparticles in water previously. It is an organic solvent-free, environmentally friendly method for peptide synthesis. In this study, we have investigated the racemization of cysteine during an aqueous based coupling reaction with MW irradiation. Under our MW-assisted protocol using WSCI and DMTMM, the coupling reaction can be performed with low levels of racemization of cysteine. We also demonstrated the synthesis of the nonapeptide oxytocin analogue, Cys(Acm)-Tyr-Ile-Gln-Asn- Cys(Acm)-Pro-Leu-Gly-NH2 using our water based MW-assisted protocol with Fmoc-amino acid nanoparticles. PMID:23517723

  9. [Ketamine racemate and S-(+)-ketamine. Cerebrovascular effects and neuroprotection following focal ischemia].

    PubMed

    Werner, C; Reeker, W; Engelhard, K; Lu, H; Kochs, E

    1997-03-01

    The phencyclidine derivative ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist with the thalamo-neocortical projection system as the primary site of action. Racemic ketamine consists of the enantiomers S(+)-ketamine and R(-)-ketamine. Racemic ketamine has never been considered an adequate anaesthetic agent in neurosurgical patients since it produces regionally specific stimulation of cerebral metabolism (CMRO2) and increases cerebral blood flow (CBF) and intracranial pressure (ICP). However, recent experiments suggest that both tracemic ketamine and S(+)-ketamine may reduce infarct size in animal models of incomplete cerebral ischaemia and brain injury. This experimental protective effect appears to be related to decreases in Ca++ influx and maintenance of brain tissue magnesium levels due to NMDA and quisqualate receptor blockade by ketamine. Studies in dogs have shown that racemic ketamine (2.0 mg/kg) increases CBF in the presence of the cerebral vasodilator N2O. In contrast, studies in rats without background anaesthesia showed increases in CBF after racemic ketamine (100 mg/kg i.p.). This suggests that the cerebrovascular effects of racemic ketamine are related to the pre-existing cerebrovascular tone induced by background anaesthetics. Cerebrovascular CO2 reactivity was maintained regardless of the baseline cerebrovascular resistance. There are several mechanisms by which racemic ketamine may increase CBF. It induces dose-dependent respiratory depression with consequent mild hypercapnia in spontaneously ventilating subjects. This produces vasodilation due to the intact cerebrovascular CO2 reactivity. Racemic ketamine also induces regional neuroexcitation, which leads to stimulation of cerebral glucose consumption in the limbic, extrapyramidal, auditory, and sensory-motor systems. This regional neuroexcitation with increased CMRO2 produces increases in CBF that can be blocked by infusion of barbiturates or benzodiazepines. However

  10. Is the required therapeutic effect always achieved by racemic switch of proton-pump inhibitors?

    PubMed Central

    Zhou, Quan; Yan, Xiao-Feng; Pan, Wen-Sheng; Zeng, Su

    2008-01-01

    Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole. PMID:18442220

  11. A patient satisfaction survey comparing levalbuterol with racemic albuterol in children.

    PubMed

    Berger, William E; Ames, Dale E; Harrison, Doug

    2004-01-01

    Patient preference studies provide important data on the impact of asthma symptoms and the effects of medication on patients' quality of life and functional activity levels. Such studies are lacking in the evaluation of short-acting beta2-agonist treatment for asthma, especially for racemic albuterol. The introduction in 1999 of levalbuterol, the (R)-isomer of racemic albuterol, has provided the opportunity to assess patient preference between racemic albuterol and levalbuterol. Studies with levalbuterol, 1.25 mg, indicated greater bronchodilation than and comparable beta2-mediated side effects to the standard 2.5-mg dose of racemic albuterol, while lower doses of levalbuterol (0.63 mg) provided comparable bronchodilation with reduced beta2-mediated side effects in patients with asthma. This study evaluated treatment satisfaction by the caregivers of children with asthma who currently use and/or have used either levalbuterol (n = 66) or racemic albuterol (n = 76). Twenty-minute-long telephone surveys were administered to caregivers, asking them to rate satisfaction with their child's asthma treatment and provide reasons for satisfaction and dissatisfaction. Significantly more caregivers administering levalbuterol (92%) were "extremely" or "very satisfied" with therapy versus those who currently administered racemic albuterol (51%; p = 0.001). Symptom relief was graded 8.7 (out of 10) for levalbuterol treatment versus 7.5 for racemic albuterol (p = 0.001). Although these differences, in part, may have been influenced by some of the study limitations (e.g., open-label, non-placebo-controlled and nonrandomized design, and potential caregiver recall bias), the statistically significant differences consistently favored levalbuterol and are consistent with results obtained from other clinical studies. The efficacy, dosing flexibility, and improved side effect profile of levalbuterol were the sources of greatest satisfaction for parents/ caregivers in the levalbuterol

  12. Enzymatic Synthesis of (S)-(-)-gamma-Methyl-gamma-butyrolactone from Racemic Methyl gamma-hydroxypentanoate Using Porcine Pancreatic Lipase: A Microscale Advanced Bioorganic Chemistry Laboratory Project

    NASA Astrophysics Data System (ADS)

    Lee, Moses

    1998-02-01

    The use of enzymes in academic as well as industrial chemical laboratories is now common, and in some cases live organisms are utilized. In this laboratory project, porcine pancreatic lipase (PPL) is used to convert a racemic sample of methyl gamma-hydroxypentanoate into gamma-methyl-gamma-butyrolactone in an effort to demonstrate the ability of enzymes to differentiate between enantiomeric substrates. This project also uses a number of chemical and spectroscopic techniques commonly used by organic and biochemists. Students are asked to complete two lactonization reactions of racemic methyl gamma-hydroxypentanoate: one is catalyzed by PPL and the other by para-toluenesulfonic acid, which produces a racemic mixture of gamma-methyl-gamma-butyrolactone. Both samples of the gamma-lactone are analyzed by TLC, purified by silica gel column chromatography, and characterized by infrared and 1H-NMR studies. While the sample of g-lactone obtained from the PPL catalyzed reaction is optically active, [alpha]D25° = -13.4° (c = 0.0098, chloroform), the sample from the acid catalyzed reaction is not. Results from 1H-NMR studies of these lactones with a mole equivalent of (R)-(-)-2,2,2-trifluoro-1-(9-anthryl)ethanol show the enantiomeric excess of the optically active lactone to be 37 + 4 % favoring the S-enantiomer.

  13. Comparative clinical trial of S-pantoprazole versus racemic pantoprazole in the treatment of gastro-esophageal reflux disease

    PubMed Central

    Pai, Vikas G; Pai, Nitin V; Thacker, Hemant P; Shinde, Jaisingh K; Mandora, Vijay P; Erram, Subhash S

    2006-01-01

    AIM: To compare the efficacy and tolerability of S-pantoprazole (20 mg once a day) versus racemic Pantoprazole (40 mg once a day) in the treatment of gastro-esophageal reflux disease (GERD). METHODS: This multi-centre, randomized, double-blind clinical trial consisted of 369 patients of either sex suffering from GERD. Patients were randomly assigned to receive either one tablet (20 mg) of S-pantoprazole once a day (test group) or 40 mg racemic pantoprazole once a day (reference group) for 28 d. Patients were evaluated for reduction in baseline on d 0, GERD symptom score on d 14 and 28, occurrence of any adverse effect during the course of therapy. Gastrointestinal (GI) endoscopy was performed in 54 patients enrolled at one of the study centers at baseline and on d 28. RESULTS: Significant reduction in the scores (mean and median) for heart burn (P < 0.0001), acid regurgitation (P < 0.0001), bloating (P < 0.0001), nausea (P < 0.0001) and dysphagia (P < 0.001) was achieved in both groups on d 14 with further reduction on continuing the therapy till 28 d. There was a statistically significant difference in the proportion of patients showing improvement in acid regurgitation and bloating on d 14 and 28 (P = 0.004 for acid regurgitation; P = 0.03 for bloating) and heart burn on d 28 (P = 0.01) between the two groups, with a higher proportion in the test group than in the reference group. Absolute risk reductions for heartburn/acid regurgitation/bloating were approximately 15% on d 14 and 10% on d 28. The relative risk reductions were 26%-33% on d 14 and 15% on d 28. GI endoscopy showed no significant difference in healing of esophagitis (P = 1) and gastric erosions (P = 0.27) between the two groups. None of the patients in either group reported any adverse effect during the course of therapy. CONCLUSION: In GERD, S-pantoprazole (20 mg) is more effective than racemic pantoprazole (40 mg) in improving symptoms of heartburn, acid regurgitation, bloating and equally

  14. Structure elucidation of the Pribnow box consensus promoter sequence by racemic DNA crystallography.

    PubMed

    Mandal, Pradeep K; Collie, Gavin W; Srivastava, Suresh C; Kauffmann, Brice; Huc, Ivan

    2016-07-01

    It has previously been shown that the use of racemic mixtures of naturally chiral macromolecules such as protein and DNA can significantly aid the crystallogenesis process, thereby addressing one of the major bottlenecks to structure determination by X-ray crystallographic methods-that of crystal growth. Although previous studies have provided convincing evidence of the applicability of the racemic crystallization technique to DNA through the study of well-characterized DNA structures, we sought to apply this method to a historically challenging DNA sequence. For this purpose we chose a non-self-complementary DNA duplex containing the biologically-relevant Pribnow box consensus sequence 'TATAAT'. Four racemic crystal structures of this previously un-crystallizable DNA target are reported (with resolutions in the range of 1.65-2.3 Å), with further crystallographic studies and structural analysis providing insight into the racemic crystallization process as well as structural details of this highly pertinent DNA sequence. PMID:27137886

  15. Disposition of Chiral and Racemic Fluoxetine and Norfluoxetine Across Childbearing

    PubMed Central

    Sit, Dorothy; Perel, James M.; Luther, James F.; Wisniewski, Stephen R.; Helsel, Joseph C.; Wisner, Katherine L.

    2011-01-01

    Objective To add to the limited data on the clinical pharmacology of antidepressants during pregnancy, we examined the dose-corrected chiral and racemic levels (level/dose) of fluoxetine (FLX) and norfluoxetine (NorFLX) during pregnancy and early postpartum. Methods The authors evaluated 17 pregnant women who received fluoxetine therapy. Doses were recorded weekly across gestation and postpartum. At 20, 30, and 36 weeks of gestation, during delivery, and 12 weeks after delivery, the depression level was assessed with the Hamilton Rating Scale for Depression (HRS-D), and plasma samples were analyzed for levels of S- and R-FLX and S- and R-NorFLX. Results The mean ratios of the chiral parent drug (S-FLX + R-FLX) to metabolite levels (S-NorFLX + R-NorFLX) decreased across pregnancy. The differences were significant between 20–36 weeks and 30–36 weeks. After delivery, the mean dose–corrected level of the active moiety S-FLX and the mean ratio of the chiral parent drug (S-FLX + R-FLX) to metabolite level (S-NorFLX + R-NorFLX) significantly increased between delivery and 12 weeks postpartum. Most of the fluoxetine-treated subjects experienced remitted depressive episodes and euthymic mood levels during pregnancy and postpartum. Conclusions The findings extend earlier reports of increased antidepressant metabolism during pregnancy and refractory metabolism after delivery. These data may inform treatment decisions related to dosing in patients who receive fluoxetine during pregnancy. PMID:20631556

  16. Chiral resolution and absolute configuration of a pair of rare racemic spirodienone sesquineolignans from Xanthium sibiricum.

    PubMed

    Shi, Yusheng; Liu, Yunbao; Li, Yong; Li, Li; Qu, Jing; Ma, Shuanggang; Yu, Shishan

    2014-10-17

    A pair of racemic spirodienone neolignan enantiomers, (±)-sibiricumin A, were isolated from the extract of the fruits of Xanthium sibiricum. The resolution of (+)- and (-)-sibiricumin A was achieved by chiral HPLC. The absolute configurations of the racemes were assigned by X-ray and by electronic circular dichroism (ECD). This experiment is the first unambiguous determination of the absolute configuration of spirodienone neolignan. PMID:25275854

  17. Enantioselective autocatalysis. II. Racemization studies on a 1,4-benzodiazepinooxazole derivative

    NASA Astrophysics Data System (ADS)

    Bonner, William A.

    1995-08-01

    Since the bromofluoro-1,4-benzodiazepinooxazole derivativeI may undergo spontaneous resolution on crystallization from methanol solution, it provides an ideal substrate on which to study the phenomenon of enantioselective autocatalysis involving spontaneous resolution under racemizing conditions (srurc). in order to augment the understanding of factors which might be important in such a process we have now undertaken to study the racemization ofI in more detail by observing its rate under a wide variety of experimental conditions.

  18. Use of After Action Reports (AARs) to Promote Organizational and Systems Learning in Emergency Preparedness

    PubMed Central

    Savoia, Elena; Agboola, Foluso; Biddinger, Paul D.

    2012-01-01

    Many public health and healthcare organizations use formal knowledge management practices to identify and disseminate the experiences gained over time. The “lessons-learned” approach is one such example of knowledge management practice applied to the wider concept of organizational learning. In the field of emergency preparedness, the lessons-learned approach stands on the assumption that learning from experience improves practice and minimizes avoidable deaths and negative economic and social consequences of disasters. In this project, we performed a structured review of AARs to analyze how lessons learned from the response to real-incidents may be used to maximize knowledge management and quality improvement practices such as the design of public health emergency preparedness (PHEP) exercises. We chose as a source of data the “Lessons Learned Information Sharing (LLIS.gov)” system, a joined program of the U.S. Department of Homeland Security DHS and FEMA that serves as the national, online repository of lessons learned, best practices, and innovative ideas. We identified recurring challenges reported by various states and local public health agencies in the response to different types of incidents. We also strived to identify the limitations of systematic learning that can be achieved due to existing weaknesses in the way AARs are developed. PMID:23066408

  19. Use of after action reports (AARs) to promote organizational and systems learning in emergency preparedness.

    PubMed

    Savoia, Elena; Agboola, Foluso; Biddinger, Paul D

    2012-08-01

    Many public health and healthcare organizations use formal knowledge management practices to identify and disseminate the experiences gained over time. The "lessons-learned" approach is one such example of knowledge management practice applied to the wider concept of organizational learning. In the field of emergency preparedness, the lessons-learned approach stands on the assumption that learning from experience improves practice and minimizes avoidable deaths and negative economic and social consequences of disasters. In this project, we performed a structured review of AARs to analyze how lessons learned from the response to real-incidents may be used to maximize knowledge management and quality improvement practices such as the design of public health emergency preparedness (PHEP) exercises. We chose as a source of data the "Lessons Learned Information Sharing (LLIS.gov)" system, a joined program of the U.S. Department of Homeland Security DHS and FEMA that serves as the national, online repository of lessons learned, best practices, and innovative ideas. We identified recurring challenges reported by various states and local public health agencies in the response to different types of incidents. We also strove to identify the limitations of systematic learning that can be achieved due to existing weaknesses in the way AARs are developed. PMID:23066408

  20. A Study on Amino Acids: Synthesis of Alpha-Aminophenylacetic Acid (Phenylglycine) and Determination of its Isoelectric Point.

    ERIC Educational Resources Information Center

    Barrelle, M.; And Others

    1983-01-01

    Background information and procedures are provided for an experimental study on aminophenylacetic acid (phenylglycine). These include physical chemistry (determination of isoelectric point by pH measurement) and organic chemistry (synthesis of an amino acid in racemic form) experiments. (JN)

  1. Experimental and theoretical study of racemization, stability and tautomerism of vitamin C stereoisomers.

    PubMed

    Dabbagh, Hossein A; Azami, Fatemeh

    2014-12-01

    Experimental degradation of vitamin C (VC) in water was monitored using specific rotation, FT-IR and (1)H NMR at room temperature and at 80-90°C. The optical activity was reduced (100%) to zero after 6 and 63 days at 80-90°C (≅25% in less than 24h) and room temperature, respectively. (1)H NMR and FT-IR was performed after these periods which indicated the formation of a complex mixture at higher stirring time and elevated temperature. These observations indicated that vitamin C is unstable in solution at room temperature or at elevated temperature. The solid VC did not lose optical activity after several mounts at room temperature. The instability of VC was related to isomerization (loss of optical activity) of the l-enantiomer either to d-enantiomer (racemization), degradation to undesired products or tautomerization to other isomers. Theoretical investigation (at B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of theory in vacuo and aqueous phases) formulated tautomerization for RS-stereoisomers of ascorbic acids (AA). The mechanism for deactivation of VC was examined. PMID:24996345

  2. Responses to the AAR-Teagle White Paper: "The Religious Studies Major in a Post-9/11 World"

    ERIC Educational Resources Information Center

    Webster, Jane S.; Buckley, James J.; Jensen, Tim; Floyd-Thomas, Stacey

    2011-01-01

    In October 2008 The American Academy of Religion published the findings of an eighteen month study (conducted with funding from the Teagle Foundation) on "The Religious Studies Major in a Post-9/11 World: New Challenges, New Opportunities." Re-published here, this AAR-Teagle White Paper provides the opportunity for four respondents to raise issues…

  3. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR).

    PubMed

    Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J; Laclette, Juan P; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

    2015-01-01

    Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest. PMID:25989346

  4. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR)

    PubMed Central

    Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J.; Laclette, Juan P.; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

    2015-01-01

    Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest. PMID:25989346

  5. A NASA F/A-18, participating in the Automated Aerial Refueling (AAR) project, flies over the Dryden

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA F/A-18 is participating in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acts as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  6. Pairwise comparison of levalbuterol versus racemic albuterol in the treatment of moderate-to-severe asthma.

    PubMed

    Pleskow, Warren W; Nelson, Harold S; Schaefer, Kendyl; Claus, Raymond; Roach, James M

    2004-01-01

    The object of this study is a post hoc pairwise comparison of levalbuterol versus racemic albuterol for asthma in a multicenter, double-blind, randomized, placebo-controlled clinical trial. The participants are patients > or =12 years of age (n = 362) with FEV1 45-70% of predicted. The patients received nebulized levalbuterol (0.63 or 1.25 mg), racemic albuterol (1.25 or 2.5 mg), or placebo t.i.d. for 4 weeks. The primary endpoints, published in Nelson HS, Bensch G, Pleskow WW, et al. Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma. J Allergy Clin Immunol 102:943-952, 1998, included comparisons of active treatments with placebo and of the combined levalbuterol with the combined racemic albuterol groups for pulmonary function and rescue medication use. After the first dose, levalbuterol 1.25 mg produced a significantly greater increase in the mean peak change in FEV1 compared with both doses of racemic albuterol (p < 0.03) in all patients and in those with more severe asthma. Levalbuterol 1.25 mg also produced a significantly greater (p < 0.05) mean area under the curve (AUC) of the FEV1 versus time plot (AUC FEV1) compared with all other treatments after the first dose in all patients and in the subset with more severe disease, illustrating better overall improvement in FEV1. Active treatment groups demonstrated significant improvements compared with the placebo group (p < 0.05), except for AUC FEV1 in the racemic albuterol 1.25-mg group at week 4. Levalbuterol in the absence of the (S)-isomer provided greater bronchodilation than the same quantity of (R)-albuterol delivered as the racemate. These data suggest that (S)-albuterol may compromise the efficacy of (R)-albuterol. PMID:15709454

  7. Halogen and trace element geochemistry in Mid-Ocean Ridge basalts from the Australian-Antarctic Ridge (AAR)

    NASA Astrophysics Data System (ADS)

    Yang, Y. S.; Seo, J. H.; Park, S. H.; Kim, T.

    2015-12-01

    Australian-Antarctic Ridge (AAR) is an extension of easternmost SE Indian Mid-Ocean Ridge (MOR).We collected volcanic glasses from the "in-axis" of the KR1 and KR2 MOR, and the overlapping zones of the KR1 MOR and the nearby seamounts ("KR1 mixing"). We determined trace and halogen elements in the glasses. Halogen concentrations and its ratios in the glasses are important to understand the mantle metasomatism and volatile recycling. 52 of the collected glasses are "primitive" (higher than 6 wt% MgO), while 3 of them have rather "evolved" composition (MgO wt% of 1.72, 2.95 and 4.15). K2O concentrations and Th/Sc ratios in the glasses show a negative correlation with its MgO concentration. Incompatible element ratios such as La/Sm are rather immobile during a magma differentiation so the ratios are important to understand mantle composition (Hofmann et al. 2003). La/Sm ratios in the glasses are 0.95 ~ 3.28 suggesting that the AAR basalts can be classified into T-MORB and E-MORB (Schilling et al., 1983). La/Sm ratios are well-correlated with incompatible elements such as U, Ba, Nb, and negatively correlated with compatible elements such as Sc, Eu2+, Mg. The AAR glasses contain detectable halogen elements. The "KR1 mixing" glasses in halogen elements are more abundant than "in-axis" the glasses. Cl is the least variable element compared to the other halogens such as Br and I in the AAR. The "KR1 mixing" glasses have the largest variations of Br/Cl ratios compared to the "in-axis" glasses. The Cl/Br and Th/Sc ratios in the "in-axis" glasses and in the "KR1 mixing" glasses show positive and negative correlations, respectively. The Br-rich glasses in the "KR1 mixing" zone might be explained by a recycled Br-rich oceanic slab of paleo-subduction or by a hydrothermal alteration in the AAR. I composition in the glasses does not show a correlation other trace elements. The K/Cl and K/Ti ratios in the AAR glasses are similar to the basalts from the Galapagos Spreading Center

  8. The Front of the Aar Massif: A Crustal-Scale Ramp Anticline?

    NASA Astrophysics Data System (ADS)

    Herwegh, Marco; Mock, Samuel; Wehrens, Philip; Baumberger, Roland; Berger, Alfons; Wangenheim, Cornelia; Glotzbach, Christoph; Kissling, Edi

    2015-04-01

    The front of the Aar Massif (Swiss Central Alps) is characterized by Paleozoic basement rocks exposed at altitudes of more than 4600m above sea level, followed by a steeply north dipping Mesozoic sedimentary cover and overlying Helvetic nappes. The sediments turn into subhorizontal orientations just few kilometers to the N, where the top of the basement is situated at depths of about 7000m below sea level. What is the origin of this vertical jump of about 12000m of the basement rocks over such short horizontal distances? Recent structural investigations at the Basement-Cover contact indicate a complex structural evolution involving reactivation of extensional faults and inversion of half-grabens during early compressional stages. In the internal parts of the Aar Massif a general steepening of the faults resulted with progressive compression. In the northern frontal part, however, a new spaced cleavage evolved, which is dipping with 20-30° to the SE. In places, the new cleavage in the basement rocks is intense and pervasive and correlates with a steepening of the basement-cover contact and its offsets of several tens to hundreds of meters. Hence strain is strongly partitioned in a large number of high strain zones, which cover a cumulative thickness of at least 2000m, eventually even much more considering subsurface continuation. The Mesozoic sediments affected by this large-scale deformation zone are either intensely ductile folded in the case of limestones or faulted and imbricated in the case of dolomites. These differences in deformation style result from the deformation conditions of about < 250-300°C, where calcite still deforms in a ductile manner, while dolomite and crystalline basement preferentially undergo brittle deformation in combination of dissolution-precipitation processes. In a large-scale point of view, we suggest that the high strain domain in the crystalline basement in fact represents a crustal-scale several kilometers wide shear zone, which

  9. Quasi-Racemic X-ray Structures of K27-Linked Ubiquitin Chains Prepared by Total Chemical Synthesis.

    PubMed

    Pan, Man; Gao, Shuai; Zheng, Yong; Tan, Xiaodan; Lan, Huan; Tan, Xianglong; Sun, Demeng; Lu, Lining; Wang, Tian; Zheng, Qingyun; Huang, Yichao; Wang, Jiawei; Liu, Lei

    2016-06-15

    Quasi-racemic crystallography has been used to determine the X-ray structures of K27-linked ubiquitin (Ub) chains prepared through total chemical synthesis. Crystal structures of K27-linked di- and tri-ubiquitins reveal that the isopeptide linkages are confined in a unique buried conformation, which provides the molecular basis for the distinctive function of K27 linkage compared to the other seven Ub chains. K27-linked di- and triUb were found to adopt different structural conformations in the crystals, one being symmetric whereas the other triangular. Furthermore, bioactivity experiments showed that the ovarian tumor family de-ubiquitinase 2 significantly favors K27-linked triUb than K27-linked diUb. K27-linked triUb represents the so-far largest chemically synthesized protein (228 amino acids) that has been crystallized to afford a high-resolution X-ray structure. PMID:27268299

  10. meso-Tetrahydropyranylperoxides: molecular structures in solution, in the crystal, and by DFT calculations and their isomerization to the racemate.

    PubMed

    Balaban, Teodor Silviu; Eichhöfer, Andreas; Ghiviriga, Ion; Hugo, Holger; Wenzel, Wolfgang

    2003-06-27

    The crystalline peroxide 3a is the main product (out of 10 theoretically possible) from the aerial peroxidation of all-cis-2,4,6-trimethyltetrahydropyran (2a). It has a similar structure both in solution and in the crystal as shown by nuclear Overhauser effects and X-ray analysis, respectively. Theoretical calculations at a density functional theory level (B3LYP/6-31G) provide insight into the stabilities of the different stereoisomers of this peroxide, accounting for the facile, acid-catalyzed isomerization from the meso form to the racemate. Peroxide 3b, which is the 2-tert-butyl analogue of 3a, out of 22 theoretically possible isomers, crystallizes in a similar meso form. As a result of crystal packing effects and the intrinsically (axial) chiral peroxy "chromophore" that deviates slightly from the antiperiplanar conformation, both enantiomorphic forms of 3b are encountered in the lattice. PMID:12816495

  11. Evaluation of Fe and Ru Pincer-Type Complexes as Catalysts for the Racemization of Secondary Benzylic Alcohols.

    PubMed

    Bornschein, Christoph; Gustafson, Karl P J; Verho, Oscar; Beller, Matthias; Bäckvall, Jan-E

    2016-08-01

    Fe and Ru pincer-type catalysts are used for the racemization of benzylic alcohols. Racemization with the Fe catalyst was achieved within 30 minutes under mild reaction conditions, with a catalyst loading as low as 2 mol %. This reaction constitutes the first example of an iron-catalyzed racemization of an alcohol. The efficiency for racemization of the Fe catalyst and its Ru analogue was evaluated for a wide range of sec-benzylic alcohols. The commercially available Ru complex proved to be highly robust and even tolerated the presence of water in the reaction mixture. PMID:27311070

  12. Enantiomeric Excesses of Acid Labile Amino Acid Precursors of the Murchison Meteorite

    NASA Technical Reports Server (NTRS)

    Pizzarello, Sandra

    1998-01-01

    Amino acids present in carbonaceous chondrite are extracted in water in part as free compounds and in approximately equal part as acid labile precursors. On the assumption that they would be free of contamination, the precursors of two Murchison amino acids that have terrestrial occurrence, alanine and glutamic acid, have been targeted for analysis of their enantiomeric ratios. Pyroglutamic acid, the precursor of glutamic acid, was found with an L-enantiomeric excess comparable to that of the free acid, while alanine's precursor, N-acetyl alanine, appears approximately racemic. Also alpha-imino propioacetic acid, a proposed end product of alanine synthesis in the meteorite, was analyzed and found racemic.

  13. Emulsification-Induced Homohelicity in Racemic Helical Polymer for Preparing Optically Active Helical Polymer Nanoparticles.

    PubMed

    Zhao, Biao; Deng, Jinrui; Deng, Jianping

    2016-04-01

    Optically active nano- and microparticles have constituted a significant category of advanced functional materials. However, constructing optically active particles derived from synthetic helical polymers still remains as a big challenge. In the present study, it is attempted to induce a racemic helical polymer (containing right- and left-handed helices in equal amount) to prefer one predominant helicity in aqueous media by using emulsifier in the presence of chiral additive (emulsification process). Excitingly, the emulsification process promotes the racemic helical polymer to unify the helicity and directly provides optically active nanoparticles constructed by chirally helical polymer. A possible mechanism is proposed to explain the emulsification-induced homohelicity effect. The present study establishes a novel strategy for preparing chirally helical polymer-derived optically active nanoparticles based on racemic helical polymers. PMID:26829250

  14. Highly efficient photochemically induced thiyl radical-mediated racemization of aliphatic amines at 30 degrees C.

    PubMed

    Routaboul, Lucie; Vanthuyne, Nicolas; Gastaldi, Stéphane; Gil, Gérard; Bertrand, Michèle

    2008-01-18

    UV irradiation in the presence of thiol enables the performance of highly efficient aliphatic amines racemization, under mild conditions at 30 degrees C. The reaction proceeds via the reversible generation of prochiral alpha-aminoalkyl radicals. The latter may result either from a redox process between the thiyl radical and the amine or from direct hydrogen atom abstraction by thiyl radical. As hydrogen atom donor, the thiol plays a crucial role. While the racemization of both primary and secondary amines were fast processes, the racemization of tertiary amines was sluggish. A tentative rationale is based on the photostimulated amine-catalyzed oxidation of the thiol into the corresponding disulfide, which makes the hydrogen atom donor concentration in the reaction medium drop up to trace amount at a rate that depends on the nature of the amine. PMID:18076189

  15. Racemized and Isomerized Proteins in Aging Rat Teeth and Eye Lens.

    PubMed

    Warmack, Rebeccah A; Mansilla, Eduardo; Goya, Rodolfo G; Clarke, Steven G

    2016-08-01

    The quantification of aspartic acid racemization in the proteins of nonmetabolically active tissues can be used as a measure of chronological aging in humans and other long-lived organisms. However, very few studies have been conducted in shorter-lived animals such as rodents, which are increasingly used as genetic and metabolic models of aging. An initial study had reported significant changes in the ratio of d- to l-aspartate in rat molars with age. Using a sensitive HPLC method for the determination of d- and l-aspartate from protein hydrolysates, we found no accumulation of d-aspartate in the molars of 17 rats that ranged in age from 2 to 44 months, and the amount of d-aspartate per molar did not correspond with molar eruption date as had been previously reported. However, developing an alternate approach, we found significant accumulation of isomerized aspartyl residues in eye lens proteins that are also formed by spontaneous degradation processes. In this study, we used the human protein l-isoaspartate/d-aspartate O-methyltransferase (PCMT1) as an analytical reagent in a sensitive and convenient procedure that could be used to rapidly examine multiple samples simultaneously. We found levels of isomerized aspartyl residues to be about 35 times higher in the lens extracts of 18-month-old rats versus 2-month-old rats, suggesting that isomerization may be an effective marker for biological aging in this range of ages. Importantly, we found that the accumulation appeared to plateau in rats of 18 months and older, indicating that potentially novel mechanisms for removing altered proteins may develop with age. PMID:26650547

  16. Racemic R,S-venlafaxine hydrochloride-DNA interaction: Experimental and computational evidence

    NASA Astrophysics Data System (ADS)

    Shahabadi, Nahid; Hadidi, Saba; Ghasemian, Zeinab; Taherpour, Avat(Arman)

    2015-06-01

    The interaction of racemic R,S-venlafaxine hydrochloride (rac-VEN) drug with calf thymus deoxyribonucleic acid (ct-DNA) was studied using various physico-chemical techniques and molecular docking at simulated physiological conditions (pH = 7.4). The fluorescence study shows that ct-DNA interacted with rac-VEN and quenched its intrinsic fluorescence in a static quenching process. These results are further supported by UV-Vis spectra. The binding constant of rac-VEN with ct-DNA (0.57 × 104) obtained from the spectroscopic techniques, which is more in keeping with the groove binding with DNA. Furthermore, the competition experiment using Hoechst33258 indicated that rac-VEN may bind to ct-DNA by a minor groove binding mode. In addition, iodide quenching effect on the fluorescence of rac-VEN before and after the interaction with ct-DNA is another evidence to groove binding. The thermodynamic parameters are calculated by van't Hoff equation, which demonstrated that hydrogen bonds and van der Waals interactions played major roles in the binding reaction. Molecular simulation studies carried out by using the AutoDock4 and Spartan10 programs. From the best docking map, we found that R and S-isomers fit in the A6T7T8/T19A18A17 region in minor groove of B-DNA. Finally, these results indicated that the docking of S-VEN-B-DNA is more stable than R-VEN-B-DNA.

  17. The "racemic approach" in the evaluation of the enantiomeric NorA efflux pump inhibition activity of 2-phenylquinoline derivatives.

    PubMed

    Carotti, Andrea; Ianni, Federica; Sabatini, Stefano; Di Michele, Alessandro; Sardella, Roccaldo; Kaatz, Glenn W; Lindner, Wolfgang; Cecchetti, Violetta; Natalini, Benedetto

    2016-09-10

    Among the mechanisms adopted by bacteria, efflux pumps (EPs) have been recognized as being significantly involved in contributing to resistance to commonly used antibacterial agents. However, little is known about their three-dimensional structures or the steric requirements for their inhibition. Lack of such knowledge includes NorA, one of the most studied Staphylococcus aureus EPs. In the present study, the use of two commercialized Cinchona alkaloid-based zwitterionic chiral stationary phases allowed the enantioseparation of four 2-((2-(4-propoxyphenyl)quinolin-4-yl)oxy)alkylamines 1-4 previously found to be potent S. aureus NorA efflux pump inhibitors when tested as racemates. In the identified optimal polar-ionic conditions (MeOH/THF/H2O-49/49/2 (v/v/v)+25mM formic acid, 12.5mM diethylamine), repeated consecutive injections of 1 allowed the isolation of sufficient amount of its enantiomers (2.6mg and 2.8mg, for (R)-1 and (S)-1, respectively) and then to evaluate their ability to inhibit the S. aureus NorA efflux pump. The biological evaluation highlighted the main contribution of the (R)-1 enantiomer to both the EtBr efflux inhibition and synergistic effect with against SA-1199B (norA+/A116E GrlA) respect to the racemate activity. The comparison between the experimental electronic circular dichroism and the time-dependent density functional theory calculations spectra of the two isolated enantiomeric fractions allowed for all compounds a clear and easy assignment of the enantiomeric elution order. PMID:27429367

  18. X-ray Structure of Native Scorpion Toxin BmBKTx1 by Racemic Protein Crystallography Using Direct Methods

    SciTech Connect

    Mandal, Kalyaneswar; Pentelute, Brad L.; Tereshko, Valentina; Kossiakoff, Anthony A.; Kent, Stephen B.H.

    2009-04-08

    Racemic protein crystallography, enabled by total chemical synthesis, has allowed us to determine the X-ray structure of native scorpion toxin BmBKTx1; direct methods were used for phase determination. This is the first example of a protein racemate that crystallized in space group I41/a.

  19. Lake Biel Holocene sediment record before and after the Aare river deviation (1878 AD)

    NASA Astrophysics Data System (ADS)

    Jeannet, Alice; Corella, Juan Pablo; Kremer, Katrina; Girardclos, Stéphanie

    2014-05-01

    Lake sediments are excellent archives of environmental and climate changes as well as human impact on lake- and river-systems. Lake Biel is a medium-sized peri-alpine lake in Switzerland, with a maximum depth of 74 m, and lies at an altitude of 429 m a.s.l. Lake Biel, which formed during the Pleistocene by glacial erosion, is part of the Aare river system. Our study focuses on the south-west part of the lake basin where the lake sedimentation was originally (i.e. naturally) mainly controlled by autochthonous sedimentation. This area is currently under a strong influence of water and sediment input from this river catchment since the Aare river deviation through the Hagneck canal in 1878. A 10.05 m long composite sediment sequence, cored from a 52 m water depth in September 2011, was built from two long cores retrieved with the ETH Zurich/Eawag Uwitec system. A radiocarbon age model indicates that the retrieved sedimentary sequence spans the last 7500 years. The upper sediments were correlated to previous short core radionuclide stratigraphy for the 1.5 m upper part (Thevenon et al., 2013). Magnetic susceptibility and density were measured by Geotek MultiSensor Core Logger at 0.5 cm resolution. Granulometry was measured with a CILAS grain sizer every 10 cm, and X-ray fluorescence (XRF) was carried out using an Avaatech core scanner at 1-cm resolution. This technique provides semi-quantitative information of the sediment elemental composition and shows how runoff and river input (Ti, Al, Si) or redox conditions (Fe/Mn) vary through time. Lake Biel sediment record suggests marked environmental changes with runoff decrease linked to climate and vegetation change during Atlantic chronobiozone, as well as a complex climate-human impact during the 'La Tène' and Roman cultural times. The most prominent recorded feature is the 10-times increase of sediment rate that occurred after the Aare river deviation through the Hagneck canal into Lake Biel in 1878. This artificial

  20. A NASA F/A-18, participating in the Automated Aerial Refueling (AAR) project, flies over the Dryden

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA F/A-18 flies over the Dryden Flight Research Center and Rogers Dry Lake on December 11, 2002. The aircraft is participating in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acts as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  1. Structure elucidation of the Pribnow box consensus promoter sequence by racemic DNA crystallography

    PubMed Central

    Mandal, Pradeep K.; Collie, Gavin W.; Srivastava, Suresh C.; Kauffmann, Brice; Huc, Ivan

    2016-01-01

    It has previously been shown that the use of racemic mixtures of naturally chiral macromolecules such as protein and DNA can significantly aid the crystallogenesis process, thereby addressing one of the major bottlenecks to structure determination by X-ray crystallographic methods—that of crystal growth. Although previous studies have provided convincing evidence of the applicability of the racemic crystallization technique to DNA through the study of well-characterized DNA structures, we sought to apply this method to a historically challenging DNA sequence. For this purpose we chose a non-self-complementary DNA duplex containing the biologically-relevant Pribnow box consensus sequence ‘TATAAT’. Four racemic crystal structures of this previously un-crystallizable DNA target are reported (with resolutions in the range of 1.65–2.3 Å), with further crystallographic studies and structural analysis providing insight into the racemic crystallization process as well as structural details of this highly pertinent DNA sequence. PMID:27137886

  2. Synthesis of a Racemic Ester and Its Lipase Catalyzed Kinetic Resolution

    NASA Astrophysics Data System (ADS)

    Stetca, Delia; Arends, Isabel W. C. E.; Hanefeld, Ulf

    2002-11-01

    A first-year organic chemistry laboratory experiment is described in which an enzyme is utilized for the kinetic resolution of a racemic ester. In the first step, the racemic ester is synthesized from racemic 1-phenylethanol and acetic anhydride in the presence of pyridine. In the second step, only one of the two enantiomers of the racemic ester is selectively hydrolyzed. This reaction is enzyme-catalyzed and it clearly demonstrates the great ease with which enzymes can be used for the synthesis of enantiomerically-enriched compounds. The two enantiomerically-enriched compounds formed are isolated and analyzed for their optical purity. In these experiments the students are exposed to enzyme chemistry in combination with standard organic methods. Indeed, all the products are purified by techniques that are applied in the research laboratory (column chromatography and distillation), ensuring that these experiments come as close to the research environment as possible. By means of these experiments, topics such as enantioselective synthesis, enzymes in synthesis, enzyme kinetics, and analytical techniques such as IR, TLC, and optical rotation can be introduced to the students.

  3. [Ketamine racemate or S-(+)-ketamine and midazolam. The effect on vigilance, efficacy and subjective findings].

    PubMed

    Doenicke, A; Kugler, J; Mayer, M; Angster, R; Hoffmann, P

    1992-10-01

    Ketamine is a racemic mixture containing equal amounts of optical isomers that have almost identical pharmacokinetic properties but different pharmacodynamic effects. The S-(+)-isomer of ketamine has about twice the anaesthetic and analgesic potency of the racemic ketamine preparation and is judged to induce less psychic emergence reactions and to be followed by a more rapid recovery of vigilance. The present study was designed to assess whether the S-(+)-isomer of ketamine is superior to the racemic mixture in cardiovascular characteristics, emergence reactions and cognitive functions, and whether side effects may be reduced or prevented by administration of midazolam prior to injection of S-(+)-ketamine. METHODS. Following ethics committee approval and informed consent, 30 volunteers were randomly allocated in this double-blind study to three groups of 10 each. Group 1 received 2 mg/kg bw racemic ketamine, group 2, 1 mg/kg bw S-(+)-ketamine and group 3, 1 mg/kg bw S-(+)-ketamine after premedication with 0.1 mg/kg midazolam i.v. Cardiovascular changes, state of vigilance, cognitive performance, subjective mood and acceptance of anaesthesia were assessed by means of haemodynamic routine monitoring, electroencephalography (EEG), psychometric tests and interview. RESULTS. The increases in mean arterial pressure and heart rate following the injection of racemic ketamine and S-(+)-ketamine were identical and the differences from baseline values significant after both. Premedication with midazolam ensured stable haemodynamics after injection of S-(+)-ketamine. EEG analysis displayed the characteristic changes well known from ketamine anaesthesia for both racemic and S-(+)-ketamine. The vigilosomnoscript showed an identical profile of vigilance up to 30 min after injection of both drugs. The vigilance status after 125 min was less impaired by S-(+)-ketamine than by racemic ketamine. Psychological assessment showed a prompter recovery of visual attentiveness and

  4. Enantioselective Regulation of Lactate Racemization by LarR in Lactobacillus plantarum

    PubMed Central

    Desguin, Benoît; Goffin, Philippe; Bakouche, Nordine; Diman, Aurélie; Viaene, Eric; Dandoy, Damien; Fontaine, Laetitia; Hallet, Bernard

    2014-01-01

    Lactobacillus plantarum is a lactic acid bacterium that produces a racemic mixture of l- and d-lactate from sugar fermentation. The interconversion of lactate isomers is performed by a lactate racemase (Lar) that is transcriptionally controlled by the l-/d-lactate ratio and maximally induced in the presence of l-lactate. We previously reported that the Lar activity depends on the expression of two divergently oriented operons: (i) the larABCDE operon encodes the nickel-dependent lactate racemase (LarA), its maturases (LarBCE), and a lactic acid channel (LarD), and (ii) the larR(MN)QO operon encodes a transcriptional regulator (LarR) and a four-component ABC-type nickel transporter [Lar(MN), in which the M and N components are fused, LarQ, and LarO]. LarR is a novel regulator of the Crp-Fnr family (PrfA group). Here, the role of LarR was further characterized in vivo and in vitro. We show that LarR is a positive regulator that is absolutely required for the expression of Lar activity. Using gel retardation experiments, we demonstrate that LarR binds to a 16-bp palindromic sequence (Lar box motif) that is present in the larR-larA intergenic region. Mutations in the Lar box strongly affect LarR binding and completely abolish transcription from the larA promoter (PlarA). Two half-Lar boxes located between the Lar box and the −35 box of PlarA promote LarR multimerization on DNA, and point mutations within one or both half-Lar boxes inhibit PlarA induction by l-lactate. Gel retardation and footprinting experiments indicate that l-lactate has a positive effect on the binding and multimerization of LarR, while d-lactate antagonizes the positive effect of l-lactate. A possible mechanism of LarR regulation by lactate enantiomers is proposed. PMID:25349156

  5. Structural Evolution in the Aar Massif (Central Alps): First attempts of linking the micron- to the kilometer-scale

    NASA Astrophysics Data System (ADS)

    Wehrens, P.; Baumberger, R.; Herwegh, M.

    2012-04-01

    The Aar massif belongs to the external massifs of the Alps and is mainly composed of granitoids and gneisses. Despite numerous detailed studies in the past decades, the overall exhumation history and the associated massif internal deformation (internal strain distribution and its evolution in time, kinematics etc.) are largely unknown at present. In this project, we aim to investigate the role of shear zones in the deformation history at a variety of scales. In this context it is important to understand their microstructural evolution, the involved deformation processes, kinematics and relative ages as well as the associated changes in rheology. A GIS-based remote-sensing structural map, verified by fieldwork, (see Baumberger et al., this volume) served as base for our investigations. Lithological differences between the units (Central Aare granite, ZAGr; Grimsel granodiorte, GrGr and gneisses) cause strain to localize along these contacts. Furthermore, the initial magmatic differentiation in the granitoids locally controls the Alpine deformational overprint because of differences in effective viscosity during solid-state deformation. This behavior is illustrated by the increase of foliation intensity and the number of shear zones per rock volume from ZAGr to GrGr. Preliminary results show that deformation at the N boundary of the Aar massif has to be distinguished from the central and the southern part. In the North steep NE-SW trending foliations and shear zones with subvertical lineations represent the major structures. The shear zones acted both as normal faults and as reverse faults, which mostly used pre-existing lithological boundaries between the different gneiss units. In a later stage, E-W trending shear zones and shear bands with moderate dipping angles cross cut the earlier structures. They always show a top to the North component and might be related to the late north directed movements of the Aar massif. Yet, no absolute age dating has been performed

  6. Amino acids in modern and fossil woods

    NASA Technical Reports Server (NTRS)

    Lee, C.; Bada, J. L.; Peterson, E.

    1976-01-01

    The amino acid composition and the extent of racemization in several modern and fossil woods are reported. The method of analysis is described, and data are presented on the total amino acid concentration, the amino acid ratios, and the enantiomeric ratios in each sample. It is found that the amino acid concentration per gram of dry wood decreases with age of the sample, that the extent of racemization increases with increasing age, and that the amounts of aspartic acid, threonine, and serine decrease relative to valine with increasing age. The relative racemization rates of amino acids in wood, bone, and aqueous solution are compared, and it is shown that racemization in wood is much slower than in bone or aqueous solution. Racemization results for woods from the Kalambo Falls area of Zambia are used to calculate a minimum age of 110,000 years for the transition between the Sangoan and Acheulian industries at that site. This result is shown to be consistent with numerous radiometric dates for older Acheulian sites in Africa and to compare well with geologically inferred dates for the beginning of the Eemian and the end of the Acheulian industry in southern Africa.

  7. Enantioselective Synthesis of (2R, 3S)- and (2S, 3R)-4,4,4-trifluoro-N-Fmoc-O-tert-butyl-threonine and their Racemization-free Incorporation into Oligopeptides via Solid-phase Synthesis

    PubMed Central

    Xiao, Nu; Jiang, Zhong-Xing; Yu, Y. Bruce

    2010-01-01

    An efficient method for the enantioselective synthesis of (2R, 3S)- and (2S, 3R)-4,4,4-trifluoro-N-Fmoc-O-tert-butyl-threonine (tfT) on multi-gram scales was developed. Absolute configurations of the two stereoisomers were ascertained by X-ray crystallography. Racemization-free coupling conditions for the incorporation of tfT into oligopeptides were then explored. For solution-phase synthesis, tfT racemization was not an issue under conventional coupling conditions. For solid-phase synthesis, the following conditions were identified to achieve racemization-free synthesis: if tfT (3.0 eq.) was not the first amino acid to be linked to the resin (1.0 eq.), the condition is: 2.7 eq. DIC/3.0 eq. HOBt as the coupling reagent at 0 °C for 20 h; if tfT (3.0 eq.) was the first amino acid to be linked to the resin (1.0 eq.), then 1.0 eq. of CuCl2 needs to be added to the coupling reagent. PMID:17702025

  8. ATF4-dependent Regulation of the JMJD3 Gene during Amino Acid Deprivation Can Be Rescued in Atf4-deficient Cells by Inhibition of Deacetylation*

    PubMed Central

    Shan, Jixiu; Fu, Lingchen; Balasubramanian, Mukundh N.; Anthony, Tracy; Kilberg, Michael S.

    2012-01-01

    Following amino acid deprivation, the amino acid response (AAR) induces transcription from specific genes through a collection of signaling mechanisms, including the GCN2-eIF2-ATF4 pathway. The present report documents that the histone demethylase JMJD3 is an activating transcription factor 4 (ATF4)-dependent target gene. The JMJD3 gene contains two AAR-induced promoter activities and chromatin immunoprecipitation (ChIP) analysis showed that the AAR leads to enhanced ATF4 recruitment to the C/EBP-ATF response element (CARE) upstream of Promoter-1. AAR-induced histone modifications across the JMJD3 gene locus occur upon ATF4 binding. Jmjd3 transcription is not induced in Atf4-knock-out cells, but the AAR-dependent activation was rescued by inhibition of histone deacetylation with trichostatin A (TSA). The TSA rescue of AAR activation in the absence of Atf4 also occurred for the Atf3 and C/EBP homology protein (Chop) genes, but not for the asparagine synthetase gene. ChIP analysis of the Jmjd3, Atf3, and Chop genes in Atf4 knock-out cells documented that activation of the AAR in the presence of TSA led to specific changes in acetylation of histone H4. The results suggest that a primary function of ATF4 is to recruit histone acetyltransferase activity to a sub-set of AAR target genes. Thus, absolute binding of ATF4 to these particular genes is not required and no ATF4 interaction with the general transcription machinery is necessary. The data are consistent with the hypothesis that ATF4 functions as a pioneer factor to alter chromatin structure and thus, enhance transcription in a gene-specific manner. PMID:22955275

  9. GAMMA DETECTOR RESPONSE/SOIL CONCENTRATION CORRELATION STUDY AT THE AAR MANUFACTURING, INC. SITE, LIVONIA, MICHIGAN

    SciTech Connect

    ALTIC, NICK A

    2013-03-22

    At the NRC's request, ORAU conducted surveys of the AAR Manufacturing site during the period of September 25 through September 27, 2012. The survey activities included walkover surveys and sampling activities. Once the survey team was onsite, the NRC personnel decided to forgo survey activities in the New Addition and the pickling area. Areas of the planned study boundary were inaccessible due to overgrowth/large pieces of concrete covering the soil surface; therefore, the study boundary was redefined. Gamma walkover scans of the site boundary and front yard identified multiple areas of elevated gamma radiation. As a result, two judgmental samples were collected. Sample results were above thorium background levels The answer to the PSQ relating to the relationship between thorium concentration in soil and NaI instrument response is Yes. NaI instrument response can be used as a predictor of Th-232 concentration in the 0 to 1 m layer. An R2 value of 0.79 was determined for the surface soil relationship, thus satisfying the DQOs. Moreover, the regression was cross-checked by comparing the predicted Th-232 soil core concentration to the average Th-232 concentration (Section 5.3.2). Based on the cross-check, the regression equation provides a reasonable estimate for the Th-232 concentration at the judgmental locations. Consideration must be given when applying this equation to other soil areas of the site. If the contamination was heterogeneously distributed, and not distributed in a discrete layer as it was in the study area, then using the regression equation to predict Th-232 concentration would not be applicable.

  10. The effects of racemization rate for age estimation of pink teeth.

    PubMed

    Sakuma, Ayaka; Saitoh, Hisako; Ishii, Namiko; Iwase, Hirotaro

    2015-03-01

    Pink teeth is thought to result from the seepage of hemoglobin caused by dental pulp decomposition. We investigated whether racemization can be applied for age estimation in cases of pink teeth where the whole tooth is used. The pink teeth used were three cases and the normal teeth for control were five mandibular canines of known age. Age of the pink teeth was calculated on the basis of regression formula obtained from the five control teeth. Only a slight error was noted between the actual and estimated ages of the pink teeth (R(2) = 0.980, r = 0.990): Cases 1-3 actually aged 23, 53, and 59 years were estimated to be 26, 52, and 60 years. Based on our results of testing pink teeth of known age, we suggest that racemization techniques allow for the age estimation of pink teeth using the same methods for normally colored teeth. PMID:25684096

  11. Crystalline CO2-based polycarbonates prepared from racemic catalyst through intramolecularly interlocked assembly

    PubMed Central

    Liu, Ye; Ren, Wei-Min; Zhang, Wei-Ping; Zhao, Rong-Rong; Lu, Xiao-Bing

    2015-01-01

    The crystalline stereocomplexed polycarbonates can be prepared by mixing enantiopure polymers with opposite configuration, which derived from the asymmetric copolymerization with CO2 using enantiopure catalyst or/and chiral epoxides. Herein, we develop a powerful strategy for producing crystalline intramolecular stereocomplexed polycarbonates from racemic catalysts, which possess similar thermal stability and crystalline behaviour in comparison with the stereocomplexes by mixing opposite enantiopure polymers. Living polymer chains shuttle between catalyst molecules with different configurations to produce diastereomeric active species which is suggested to be responsible for the formation of isotactic multiblock polycarbonates in racemic bimetallic cobalt catalyst-mediated stereoselective copolymerization of CO2 and meso-epoxides. Solid-state NMR spectroscopy study suggests that the interaction in the carbonyl and methine regions is responsible for the strong crystallization capacity and compact package structure in the crystalline polycarbonates. PMID:26469884

  12. A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography

    DOE PAGESBeta

    Bunker, Richard D.; Mandal, Kalyaneswar; Bashiri, Ghader; Chaston, Jessica J.; Pentelute, Bradley L.; Lott, J. Shaun; Kent, Stephen B. H.; Baker, Edward N.

    2015-04-07

    Racemic protein crystallography was used to determine the X-ray structure of the predicted Mycobacterium tuberculosis protein Rv1738, which had been completely recalcitrant to crystallization in its natural L-form. Native chemical ligation was used to synthesize both L-protein and D-protein enantiomers of Rv1738. Crystallization of the racemic {D-protein + L-protein} mixture was immediately successful. The resulting crystals diffracted to high resolution and also enabled facile structure determination because of the quantized phases of the data from centrosymmetric crystals. The X-ray structure of Rv1738 revealed striking similarity with bacterial hibernation factors, despite minimal sequence similarity. As a result, we predict that Rv1738,more » which is highly up-regulated in conditions that mimic the onset of persistence, helps trigger dormancy by association with the bacterial ribosome.« less

  13. Radiation Damage and Racemic Protein Crystallography Reveal the Unique Structure of the GASA/Snakin Protein Superfamily.

    PubMed

    Yeung, Ho; Squire, Christopher J; Yosaatmadja, Yuliana; Panjikar, Santosh; López, Gemma; Molina, Antonio; Baker, Edward N; Harris, Paul W R; Brimble, Margaret A

    2016-07-01

    Proteins from the GASA/snakin superfamily are common in plant proteomes and have diverse functions, including hormonal crosstalk, development, and defense. One 63-residue member of this family, snakin-1, an antimicrobial protein from potatoes, has previously been chemically synthesized in a fully active form. Herein the 1.5 Å structure of snakin-1, determined by a novel combination of racemic protein crystallization and radiation-damage-induced phasing (RIP), is reported. Racemic crystals of snakin-1 and quasi-racemic crystals incorporating an unnatural 4-iodophenylalanine residue were prepared from chemically synthesized d- and l-proteins. Breakage of the C-I bonds in the quasi-racemic crystals facilitated structure determination by RIP. The crystal structure reveals a unique protein fold with six disulfide crosslinks, presenting a distinct electrostatic surface that may target the protein to microbial cell surfaces. PMID:27145301

  14. Stabilization of the Columnar Mesophase of Perylenediimide by Racemic Triple Tails.

    PubMed

    Pereira de Oliveira Santos, Deise M; Belarmino Cabral, Marilia G; Bentaleb, Ahmed; Cristiano, Rodrigo; Gallardo, Hugo; Durola, Fabien; Bock, Harald

    2016-05-23

    Whereas perylene tetracarboxdiimides derived from amino-n-alkanes if at all only show monotropic (thermodynamically unstable) mesogenic self-assembly, the hexagonal columnar liquid crystalline state can be stabilized over a broad temperature range with doubly branched, doubly racemic alkyl residues. An improved tendency to homeotropic surface orientation is observed, and the orientation of the liquid crystalline domains is maintained upon cycling through the crystalline state at room temperature. PMID:27145525

  15. From Racemic Alcohols to Enantiopure Amines: Ru-Catalyzed Diastereoselective Amination

    PubMed Central

    2015-01-01

    A commercially available ruthenium(II) PNP-type pincer catalyst (Ru-Macho) promotes the formation of α-chiral tert-butanesulfinylamines from racemic secondary alcohols and Ellman’s chiral tert-butanesulfinamide via a hydrogen borrowing strategy. The formation of α-chiral tert-butanesulfinylamines occurs in yields ranging from 31% to 89% with most examples giving >95:5 dr. PMID:25170560

  16. From racemic alcohols to enantiopure amines: Ru-catalyzed diastereoselective amination.

    PubMed

    Oldenhuis, Nathan J; Dong, Vy M; Guan, Zhibin

    2014-09-10

    A commercially available ruthenium(II) PNP-type pincer catalyst (Ru-Macho) promotes the formation of α-chiral tert-butanesulfinylamines from racemic secondary alcohols and Ellman's chiral tert-butanesulfinamide via a hydrogen borrowing strategy. The formation of α-chiral tert-butanesulfinylamines occurs in yields ranging from 31% to 89% with most examples giving >95:5 dr. PMID:25170560

  17. Racemization as a stereochemical measure of dynamics and robustness in shape-shifting organic molecules

    PubMed Central

    He, Maggie; Bode, Jeffrey W.

    2011-01-01

    Bullvalene is a structurally unique dynamic molecule thought to interconvert among 1.2 million degenerate isomers. The incorporation of different chemical substituents onto the bullvalene core should lead to a “shape-shifting” molecule that can interconvert among thousands of discrete structural isomers. Previous NMR spectroscopy and HPLC studies on substituted bullvalenes ascertained the fact that these compounds are dynamic, but they could not attest to whether the molecules are only interconverting among only a few isomers or if a multitude of structures are being accessed. Here we confirm the remarkable shape-shifting property of a tetrasubstituted bullvalene by means of a racemization experiment. We show that a single, though fleeting, chiral, enantioenriched tetrasubstituted bullvalene isomer can spontaneously equilibrate to a racemic population of dynamic compounds. Despite the fact that conversion from one enantiomer of a bullvalene isomer to the other may require dozens or even hundreds of rearrangements and involve many potential pathways, CD spectroscopy and HPLC analysis of different bullvalene populations showed that multiple pathways exist and result in the complete racemization of an initial enantioenriched chiral bullvalene. These oligosubstituted bullvalenes represent a very rare example of an entity that can spontaneously transform itself into different discrete structures using ambient thermal energy. The confirmation that these shape-shifting organic molecules are chemically robust yet structurally dynamic is an important step toward their further use as materials, sensors, and biologically active compounds. PMID:21873220

  18. Internal structure of the Aar Massif: What can we learn in terms of exploration for deep geothermal energy?

    NASA Astrophysics Data System (ADS)

    Herwegh, Marco; Baumberger, Roland; Wehrens, Philip; Schubert, Raphael; Berger, Alfons; Maeder, Urs; Spillmann, Thomas

    2014-05-01

    The successful use of deep geothermal energy requires 3D flow paths, which allow an efficient heat exchange between the surrounding host rocks and the circulating fluids. Recent attempts to exploit this energy resource clearly demonstrate that the new technology is facing sever problems. Some major problems are related to the prediction of permeability, the 3D structure of the flow paths and the mechanical responses during elevated fluid pressures at depths of several kilometers. Although seemingly new in a technical perspective, nature is facing and solving similar problems since the beginning of the Alpine orogeny. Based on detailed studies in the Hasli Valley (Aar Massif) we can demonstrate that deformation and fluid flow are strongly localized along mechanical anisotropies (e.g. lithological variations, brittle and ductile faults). Some of them already evolved during Variscan and post-Variscan times. Interestingly, these inherited structures are reactivated over and over again during the Alpine orogeny. Their reactivation occurred at depths of ~13-15 km with elevated temperatures (400-475°C) and involved both ductile and brittle deformation processes. Brittle deformation in form of hydrofracking was always present due to the circulating fluids. It is this process, which was and still is responsible for seismic activity. With progressive uplift and exhumation of the Aar Massif, ductile deformation structures became replaced by brittle cataclasites and fault gouges during fault activity at shallower crustal levels. Existing hydrotest data from the Grimsel Test Site (Nagra's underground research laboratory) indicate that these brittle successors of the ductile shear zones are domains of enhanced recent fluid percolation. Note that although being exposed today, the continuation of these fault structures are still active at depth in both brittle and ductile deformation modes, a fact that can be inferred from recent uplift rates and the active seismicity. On the

  19. 3-Dimethylphosphinothioyl-2(3H)-oxazolone (MPTO), a promising new reagent for racemization-free couplings.

    PubMed

    Katoh, T; Ueki, M

    1993-09-01

    3-Dimethylphosphinothioyl-2(3H)-oxazolone (MPTO) was synthesized, and its ability to effect racemization-free couplings and cyclization of a peptide and its C-terminal epimer was examined. MPTO showed good reactivity in aprotic polar solvents such as N,N-dimethylformamide (DMF) and N-methylpyrrolidone. In reactivity MPTO resembles DPPA and dimethylphosphinothioyl azide (MPTA) previously developed by us, but it is much better than these reagents because the side reactions specific to the azide method could be avoided. In coupling of Z-Gly-Val-OH with H-Val-OMe in DMF at 0 degree C, no racemization was observed without use of racemization-suppressing additives. Slight racemization observed at room temperature could be completely suppressed by addition of HOBt but not by HOSu. The utility of MPTO was demonstrated by the synthesis of cyclo-(D-Trp-D-Glu(OBzl)-Ala-D-Val-Leu), an intermediate for an endothelin-binding inhibitor BE 18257A. In a comparative study using DPPA, MPTA and MPTO, no racemization was observed for MPTA or MPTO, while DPPA caused considerable racemization. When MPTO was used in the presence of HOBt rapid cyclization (3 h at RT) occurred to give the optically pure cyclic product. PMID:8225782

  20. An Integrated Experimental and Computational Approach for Characterizing the Kinetics and Mechanism of Triadimefon Racemization.

    PubMed

    Cheng, Qianyi; Teng, Quincy; Marchitti, Satori A; Dillingham, Caleb M; Kenneke, John F

    2016-09-01

    Enantiomers of chiral molecules commonly exhibit differing pharmacokinetics and toxicities, which can introduce significant uncertainty when evaluating biological and environmental fates and potential risks to humans and the environment. However, racemization (the irreversible transformation of one enantiomer into the racemic mixture) and enantiomerization (the reversible conversion of one enantiomer into the other) are poorly understood. To better understand these processes, we investigated the chiral fungicide, triadimefon, which undergoes racemization in soils, water, and organic solvents. Nuclear magnetic resonance (NMR) and gas chromatography / mass spectrometry (GC/MS) techniques were used to measure the rates of enantiomerization and racemization, deuterium isotope effects, and activation energies for triadimefon in H2 O and D2 O. From these results we were able to determine that: 1) the alpha-carbonyl carbon of triadimefon is the reaction site; 2) cleavage of the C-H (C-D) bond is the rate-determining step; 3) the reaction is base-catalyzed; and 4) the reaction likely involves a symmetrical intermediate. The B3LYP/6-311 + G** level of theory was used to compute optimized geometries, harmonic vibrational frequencies, nature population analysis, and intrinsic reaction coordinates for triadimefon in water and three racemization pathways were hypothesized. This work provides an initial step in developing predictive, structure-based models that are needed to identify compounds of concern that may undergo racemization. Chirality 28:633-641, 2016. © 2016 Wiley Periodicals, Inc. PMID:27479933

  1. Identification of trends and patterns in sediment geochemistry from the Aare delta plain, Swiss Alps.

    NASA Astrophysics Data System (ADS)

    Carvalho, Filipe; Schulte, Lothar

    2015-04-01

    The study of fluvial systems by means of sediment cores is one of the most interesting approaches to understand the spatial and temporal pattern of river dynamics under the influence of different driving forces such as climate variability and human activities. This work focuses on the analysis of the geochemistry of fluvial sediments from the Aare delta plain in the Swiss Alps.The analysis of sediment cores allowed the identification of trends and patterns in sediment geochemistry. It was possible to identify diverse sedimentation phases in the delta plain, marked by differences in sedimentation processes and characterized by decreasing grain size sequences. It is worth mentioning the importance of peat formations in this sedimentary environment, reaching several centimeters thick in some cases. These horizons are normally associated with very low concentrations of chemical elements from the mineral fraction, such as Si, Al, Fe, and K. The general trends in geochemistry indicate the dominance of elements such as Al and Si, which have similar variability in all cores. It is noted that these elements have a reasonably good correlation with grain size and inverse relation with organic matter content. Factor analysis was used to study the geochemical data set of 3 sediment cores. This analysis is based on a statistical description of the variability of the correlated data where a smaller number of not observed variables are obtained (factors). Factor analysis attempts to find joint variation of the data series and presents that response as unobservable latent variables. In this study, factor analysis was conducted with the major chemical elements: Al, Si, P, K, Ca, Ti, Mn, Fe, Cu, Zn, Pb and also the percentage of TOC. Variations of these 12 inorganic and organic elements are reflected in two unobserved variables, factor 1 and factor 2. Factor analysis has enabled the recognition of two clusters: 1) a group of elements that include the TOC and metals, which are

  2. Rhodium-Catalyzed Asymmetric Cycloisomerization and Parallel Kinetic Resolution of Racemic Oxabicycles.

    PubMed

    Loh, Charles C J; Schmid, Matthias; Webster, Robert; Yen, Andy; Yazdi, Shabnam K; Franke, Patrick T; Lautens, Mark

    2016-08-16

    While desymmetrizations by intermolecular asymmetric ring-opening reactions of oxabicyclic alkenes with various nucleophiles have been reported over the past two decades, the demonstration of an intramolecular variant is unknown. Reported herein is the first rhodium-catalyzed asymmetric cycloisomerization of meso-oxabicyclic alkenes tethered to bridgehead nucleophiles, thus providing access to tricyclic scaffolds through a myriad of enantioselective C-O, C-N, and C-C bond formations. Moreover, we also demonstrate a unique parallel kinetic resolution, whereby racemic oxabicycles bearing two different bridgehead nucleophiles can be resolved enantioselectively. PMID:27416818

  3. X-ray structure of snow flea antifreeze protein determined by racemic crystallization of synthetic protein enantiomers.

    PubMed

    Pentelute, Brad L; Gates, Zachary P; Tereshko, Valentina; Dashnau, Jennifer L; Vanderkooi, Jane M; Kossiakoff, Anthony A; Kent, Stephen B H

    2008-07-30

    Chemical protein synthesis and racemic protein crystallization were used to determine the X-ray structure of the snow flea antifreeze protein (sfAFP). Crystal formation from a racemic solution containing equal amounts of the chemically synthesized proteins d-sfAFP and l-sfAFP occurred much more readily than for l-sfAFP alone. More facile crystal formation also occurred from a quasi-racemic mixture of d-sfAFP and l-Se-sfAFP, a chemical protein analogue that contains an additional -SeCH2- moiety at one residue and thus differs slightly from the true enantiomer. Multiple wavelength anomalous dispersion (MAD) phasing from quasi-racemate crystals was then used to determine the X-ray structure of the sfAFP protein molecule. The resulting model was used to solve by molecular replacement the X-ray structure of l-sfAFP to a resolution of 0.98 A. The l-sfAFP molecule is made up of six antiparallel left-handed PPII helixes, stacked in two sets of three, to form a compact brick-like structure with one hydrophilic face and one hydrophobic face. This is a novel experimental protein structure and closely resembles a structural model proposed for sfAFP. These results illustrate the utility of total chemical synthesis combined with racemic crystallization and X-ray crystallography for determining the unknown structure of a protein. PMID:18598029

  4. X-ray Structure of Snow Flea Antifreeze Protein Determined by Racemic Crystallization of Synthetic Protein Enantiomers

    SciTech Connect

    Pentelute, Brad L.; Gates, Zachary P.; Tereshko, Valentina; Dashnau, Jennifer L.; Vanderkooi, Jane M.; Kossiakoff, Anthony A.; Kent, Stephen B.H.

    2008-08-20

    Chemical protein synthesis and racemic protein crystallization were used to determine the X-ray structure of the snow flea antifreeze protein (sfAFP). Crystal formation from a racemic solution containing equal amounts of the chemically synthesized proteins d-sfAFP and l-sfAFP occurred much more readily than for l-sfAFP alone. More facile crystal formation also occurred from a quasi-racemic mixture of d-sfAFP and l-Se-sfAFP, a chemical protein analogue that contains an additional -SeCH2- moiety at one residue and thus differs slightly from the true enantiomer. Multiple wavelength anomalous dispersion (MAD) phasing from quasi-racemate crystals was then used to determine the X-ray structure of the sfAFP protein molecule. The resulting model was used to solve by molecular replacement the X-ray structure of l-sfAFP to a resolution of 0.98 {angstrom}. The l-sfAFP molecule is made up of six antiparallel left-handed PPII helixes, stacked in two sets of three, to form a compact brick-like structure with one hydrophilic face and one hydrophobic face. This is a novel experimental protein structure and closely resembles a structural model proposed for sfAFP. These results illustrate the utility of total chemical synthesis combined with racemic crystallization and X-ray crystallography for determining the unknown structure of a protein.

  5. Origin, Microbiology, Nutrition, and Pharmacology of D-Amino Acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposure of food proteins to certain processing conditions induces two major chemical changes: racemization of all L-amino acids (LAA) to D-amino acids (DAA) and concurrent formation of crosslinked amino acids such as lysinoalanine (LAL). The diet contains both processing-induced and naturally-form...

  6. Dynamic kinetic resolution of secondary alcohols combining enzyme-catalyzed transesterification and zeolite-catalyzed racemization.

    PubMed

    Zhu, Yongzhong; Fow, Kam-Loon; Chuah, Gaik-Khuan; Jaenicke, Stephan

    2007-01-01

    Hydrophobic zeolite beta containing low concentrations of Zr or Al was found to be a good catalyst for the racemization of 1-phenylethanol. The formation of styrene as a side product could be minimized by reducing the metal concentration in the zeolite beta. Combined with an immobilized lipase from Candida antarctica, the dynamic kinetic resolution of 1-phenylethanol to the (R)-phenylethylester can be achieved with high yield and selectivity. The reaction was best conducted in toluene as solvent at 60 degrees C, with higher temperatures leading to a loss in the enantioselectivity of the formed ester. By using high-molecular-weight acyl-transfer reagents, such as vinyl butyrate or vinyl octanoate, a high enantiomeric excess of the product esters of 92 and 98 %, respectively, could be achieved. This is attributed to a steric effect: the bulky ester is less able to enter the pore space of the zeolite catalyst where the active sites for racemization are localized. Close to 100 % conversion of the alcohol was achieved within 2 h. If the more common acyl donor, isopropenyl acetate, was used, the enantiomeric excess (ee) of the formed ester was only 67 %, and the reaction was considerably slower. PMID:17004277

  7. Enzymatic Hydrolytic Resolution of Racemic Ibuprofen Ethyl Ester Using an Ionic Liquid as Cosolvent.

    PubMed

    Wei, Tao; Yang, Kunpeng; Bai, Bing; Zang, Jie; Yu, Xuan; Mao, Duobin

    2016-01-01

    The aim of this study was to develop an ionic liquid (IL) system for the enzymatic resolution of racemic ibuprofen ethyl ester to produce (S)-ibuprofen. Nineteen ILs were selected for use in buffer systems to investigate the effects of ILs as cosolvents for the production of (S)-ibuprofen using thermostable esterase (EST10) from Thermotoga maritima. Analysis of the catalytic efficiency and conformation of EST10 showed that [OmPy][BF₄] was the best medium for the EST10-catalyzed production of (S)-ibuprofen. The maximum degree of conversion degree (47.4%), enantiomeric excess of (S)-ibuprofen (96.6%) and enantiomeric ratio of EST10 (177.0) were achieved with an EST10 concentration of 15 mg/mL, racemic ibuprofen ethyl ester concentration of 150 mM, at 75 °C , with a reaction time of 10 h. The reaction time needed to achieve the highest yield of (S)-ibuprofen was decreased from 24 h to 10 h. These results are relevant to the proposed application of ILs as solvents for the EST10-catalyzed production of (S)-ibuprofen. PMID:27420042

  8. Kinetic Resolution of Racemic Allylic Alcohols by Catalytic Asymmetric Substitution of the OH Group with Monosubstituted Hydrazines.

    PubMed

    Yan, Liang; Xu, Jing-Kun; Huang, Chao-Fan; He, Zeng-Yang; Xu, Ya-Nan; Tian, Shi-Kai

    2016-09-01

    A new strategy has been established for the kinetic resolution of racemic allylic alcohols through a palladium/sulfonyl-hydrazide-catalyzed asymmetric OH-substitution under mild conditions. In the presence of 1 mol % [Pd(allyl)Cl]2 , 4 mol % (S)-SegPhos, and 10 mol % 2,5-dichlorobenzenesulfonyl hydrazide, a range of racemic allylic alcohols were smoothly resolved with selectivity factors of more than 400 through an asymmetric allylic alkylation of monosubstituted hydrazines under air at room temperature. Importantly, this kinetic resolution process provided various allylic alcohols and allylic hydrazine derivatives with high enantiopurity. PMID:27339655

  9. Organic geochemistry of amino acids: Precambrian to recent

    SciTech Connect

    Engel, M.H.; Macko, S.A.

    1985-01-01

    Since the discovery of amino acids in fossils (Abelson, 1954), considerable effort has been made to elucidate the origin and distribution of amino acids in geologic materials. Racemization and decomposition reactions of amino acids and peptides derived via the natural hydrolysis of protein constituents of organisms have been extensively studied. While the ubiquity of amino acids presents a challenge for discerning their indigeneity in geologic samples, careful analyses have resulted in successful applications of amino acid racemization and decomposition reactions for investigations of geochronologic, paleoclimatic, stratigraphic, diagenetic and chemotaxonomic problems for Quaternary age samples. An investigation of amino acids in sediments from Baffin Island fjords indicates that their distribution may also provide data with respect to the relative contributions of marine and terrigenous organic matter to recent sediments. While the absence of unstable amino acids and the presence of racemic amino acids in a sample may preclude very recent contamination, the possibility of retardation of amino acid racemization rates subsequent to geopolymer formation must also be considered. Studies of amino acids in Paleozoic, Mesozoic and early Cenozoic age samples are limited. Precambrian samples, however, have received much attention, given the potential (however slight) for isolating compounds representative of the earliest living systems. A future approach for elucidating the origin(s) of amino acids in ancient samples may be analyses of their individual stable isotopic compositions.

  10. Synthesis of α-aminoboronic acids.

    PubMed

    Andrés, Patricia; Ballano, Gema; Calaza, M Isabel; Cativiela, Carlos

    2016-04-21

    This review describes available methods for the preparation of α-aminoboronic acids in their racemic or in their enantiopure form. Both, highly stereoselective syntheses and asymmetric procedures leading to the stereocontrolled generation of α-aminoboronic acid derivatives are included. The preparation of acyclic, carbocyclic and azacyclic α-aminoboronic acid derivatives is covered. Within each section, the different synthetic approaches have been classified according to the key bond which is formed to complete the α-aminoboronic acid skeleton. PMID:26853637

  11. Lactate Racemization as a Rescue Pathway for Supplying d-Lactate to the Cell Wall Biosynthesis Machinery in Lactobacillus plantarum

    PubMed Central

    Goffin, Philippe; Deghorain, Marie; Mainardi, Jean-Luc; Tytgat, Isabelle; Champomier-Vergès, Marie-Christine; Kleerebezem, Michiel; Hols, Pascal

    2005-01-01

    Lactobacillus plantarum is a lactic acid bacterium that produces d- and l-lactate using stereospecific NAD-dependent lactate dehydrogenases (LdhD and LdhL, respectively). However, reduction of glycolytic pyruvate by LdhD is not the only pathway for d-lactate production since a mutant defective in this activity still produces both lactate isomers (T. Ferain, J. N. Hobbs, Jr., J. Richardson, N. Bernard, D. Garmyn, P. Hols, N. E. Allen, and J. Delcour, J. Bacteriol. 178:5431-5437, 1996). Production of d-lactate in this species has been shown to be connected to cell wall biosynthesis through its incorporation as the last residue of the muramoyl-pentadepsipeptide peptidoglycan precursor. This particular feature leads to natural resistance to high concentrations of vancomycin. In the present study, we show that L. plantarum possesses two pathways for d-lactate production: the LdhD enzyme and a lactate racemase, whose expression requires l-lactate. We report the cloning of a six-gene operon, which is involved in lactate racemization activity and is positively regulated by l-lactate. Deletion of this operon in an L. plantarum strain that is devoid of LdhD activity leads to the exclusive production of l-lactate. As a consequence, peptidoglycan biosynthesis is affected, and growth of this mutant is d-lactate dependent. We also show that the growth defect can be partially restored by expression of the d-alanyl-d-alanine-forming Ddl ligase from Lactococcus lactis, or by supplementation with various d-2-hydroxy acids but not d-2-amino acids, leading to variable vancomycin resistance levels. This suggests that L. plantarum is unable to efficiently synthesize peptidoglycan precursors ending in d-alanine and that the cell wall biosynthesis machinery in this species is specifically dedicated to the production of peptidoglycan precursors ending in d-lactate. In this context, the lactate racemase could thus provide the bacterium with a rescue pathway for d-lactate production upon

  12. MAPK signaling triggers transcriptional induction of cFOS during amino acid limitation of HepG2 cells.

    PubMed

    Shan, Jixiu; Donelan, William; Hayner, Jaclyn N; Zhang, Fan; Dudenhausen, Elizabeth E; Kilberg, Michael S

    2015-03-01

    Amino acid (AA) deprivation in mammalian cells activates a collection of signaling cascades known as the AA response (AAR), which is characterized by transcriptional induction of stress-related genes, including FBJ murine osteosarcoma viral oncogene homolog (cFOS). The present study established that the signaling mechanism underlying the AA-dependent transcriptional regulation of the cFOS gene in HepG2 human hepatocellular carcinoma cells is independent of the classic GCN2-eIF2-ATF4 pathway. Instead, a RAS-RAF-MEK-ERK cascade mediates AAR signaling to the cFOS gene. Increased cFOS transcription is observed from 4-24 h after AAR-activation, exhibiting little or no overlap with the rapid and transient increase triggered by the well-known serum response. Furthermore, serum is not required for the AA-responsiveness of the cFOS gene and no phosphorylation of promoter-bound serum response factor (SRF) is observed. The ERK-phosphorylated transcription factor E-twenty six-like (p-ELK1) is increased in its association with the cFOS promoter after activation of the AAR. This research identified cFOS as a target of the AAR and further highlights the importance of AA-responsive MAPK signaling in HepG2 cells. PMID:25523140

  13. Randomized placebo controlled assessment of airway inflammation due to racemic albuterol and levalbuterol via exhaled nitric oxide testing

    PubMed Central

    Freiler, John F; Arora, Rajiv; Kelley, Thomas C; Hagan, Larry; Allan, Patrick F

    2006-01-01

    Study Objectives The S-stereoisomer found in racemic albuterol may have associated proinflammatory properties. We tested the hypothesis that airway inflammation as assessed by exhaled nitric oxide is no different in patients with COPD when using racemic albuterol relative to levalbuterol or placebo. Measurements Twelve mild to moderate COPD patients were assigned to five days each of nebulized racemic albuterol, levalbuterol, and saline placebo. Before and after each course of treatment, airway inflammation was assessed via exhaled nitric oxide breath testing. Secondary functional outcomes that were measured included spirometry, a functional assessment utilizing a six-minute walk, and symptoms score using the University of California, San Diego Shortness of Breath Questionnaire. Results There was no statistically significant difference in pre and post FeNO levels within and between treatment groups (p = 0.121). There were also no significant differences within or between treatment groups for the secondary outcome measurements of FEV1 (p = 0.913), functional assessment utilizing a six-minute walk (p = 0.838) and the symptom scores using Shortness of Breath Questionnaire (p = 0.500). Conclusion We found no difference in mild to moderate COPD patients treated with racemic albuterol, levalbuterol or placebo for measurement of exhaled nitric oxide or the secondary outcomes that were measured. PMID:18044102

  14. S-Methylidene Agents: Preparation of Chiral Non-Racemic Heterocycles

    PubMed Central

    Forbes, David C.; Bettigeri, Sampada V.; Patrawala, Samit A.; Pischek, Susanna C.; Standen, Michael C.

    2008-01-01

    Reaction of sulfur ylide with aldehyde, imine, and ketone functionality affords the desired three-membered heterocycle in excellent yield. The sulfur ylide is generated in situ upon decarboxylation of carboxymethylsulfonium betaine functionality. Of the seven carboxymethylsulfonium betaine derivatives surveyed, the highest level of conversion of π-acceptor to heterocycle was obtained having S-methyl and S-phenyl functionality bound to a thioacetate derivative. Methylene aziridinations and epoxidations involving the decarboxylation of carboxymethylsulfonium betaine functionality complements existing technologies with the advantages of the reaction protocol, levels of conversion and scope. While moderate levels of diastereocontrol were observed in the aziridination of imine functionality, the four oxiranes resolved using Jacobsen’s Co(II)-salen complex were obtained in both high yield and enantioselectivity. The isolated chiral non-racemic oxiranes constitute the formal synthesis of chelonin-B and combretastatin starting from 3-bromo-4-methoxybenzaldehyde and 3,4,5-trimethoxybenzaldehyde respectively. PMID:20049065

  15. A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography.

    PubMed

    Bunker, Richard D; Mandal, Kalyaneswar; Bashiri, Ghader; Chaston, Jessica J; Pentelute, Bradley L; Lott, J Shaun; Kent, Stephen B H; Baker, Edward N

    2015-04-01

    Protein 3D structure can be a powerful predictor of function, but it often faces a critical roadblock at the crystallization step. Rv1738, a protein from Mycobacterium tuberculosis that is strongly implicated in the onset of nonreplicating persistence, and thereby latent tuberculosis, resisted extensive attempts at crystallization. Chemical synthesis of the L- and D-enantiomeric forms of Rv1738 enabled facile crystallization of the D/L-racemic mixture. The structure was solved by an ab initio approach that took advantage of the quantized phases characteristic of diffraction by centrosymmetric crystals. The structure, containing L- and D-dimers in a centrosymmetric space group, revealed unexpected homology with bacterial hibernation-promoting factors that bind to ribosomes and suppress translation. This suggests that the functional role of Rv1738 is to contribute to the shutdown of ribosomal protein synthesis during the onset of nonreplicating persistence of M. tuberculosis. PMID:25831534

  16. A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography

    PubMed Central

    Bunker, Richard D.; Mandal, Kalyaneswar; Bashiri, Ghader; Chaston, Jessica J.; Pentelute, Bradley L.; Lott, J. Shaun; Kent, Stephen B. H.; Baker, Edward N.

    2015-01-01

    Protein 3D structure can be a powerful predictor of function, but it often faces a critical roadblock at the crystallization step. Rv1738, a protein from Mycobacterium tuberculosis that is strongly implicated in the onset of nonreplicating persistence, and thereby latent tuberculosis, resisted extensive attempts at crystallization. Chemical synthesis of the l- and d-enantiomeric forms of Rv1738 enabled facile crystallization of the d/l-racemic mixture. The structure was solved by an ab initio approach that took advantage of the quantized phases characteristic of diffraction by centrosymmetric crystals. The structure, containing l- and d-dimers in a centrosymmetric space group, revealed unexpected homology with bacterial hibernation-promoting factors that bind to ribosomes and suppress translation. This suggests that the functional role of Rv1738 is to contribute to the shutdown of ribosomal protein synthesis during the onset of nonreplicating persistence of M. tuberculosis. PMID:25831534

  17. Kinetic resolution of 2-hydroxybutanoate racemic mixtures by NAD-independent L-lactate dehydrogenase.

    PubMed

    Gao, Chao; Zhang, Wen; Ma, Cuiqing; Liu, Peng; Xu, Ping

    2011-04-01

    Optically active D-2-hydroxybutanoate is an important building block intermediate for medicines and biodegradable poly(2-hydroxybutanoate). Kinetic resolution of racemic 2-hydroxybutanoate may be a green and desirable alternative for D-2-hydroxybutanoate production. In this work, D-2-hydroxybutanoate at a high concentration (0.197 M) and a high enantiomeric excess (99.1%) was produced by an NAD-independent L-lactate dehydrogenase (L-iLDH) containing biocatalyst. 2-Oxobutanoate, another important intermediate, was co-produced at a high concentration (0.193 M). Using a simple ion exchange process with the macroporous anion exchange resin D301, D-2-hydroxybutanoate was separated from the biotransformation system with a high recovery of 84.7%. PMID:21295977

  18. Non-racemic Antifolates Stereo-selectively Recruit Alternate Cofactors and Overcome Resistance in S. aureus

    PubMed Central

    Keshipeddy, Santosh; Reeve, Stephanie M.; Anderson, Amy C.; Wright, Dennis L.

    2016-01-01

    While antifolates such as Bactrim (trimethoprim-sulfamethoxazole; TMP-SMX) continue to play an important role in treating community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), resistance-conferring mutations, specifically F98Y of dihydrofolate reductase (DHFR), have arisen and compromise continued use. In an attempt to extend the lifetime of this important class, we have developed a class of propargyl-linked antifolates (PLAs) that exhibit potent inhibition of the enzyme and bacterial strains. Probing the role of the configuration at the single propargylic stereocenter in these inhibitors required us to develop a new approach to non-racemic 3-aryl-1-butyne building blocks by the pairwise use of asymmetric conjugate addition and aldehyde dehydration protocols. Using this new route, a series of non-racemic PLA inhibitors was prepared and shown to possess potent enzyme inhibition (IC50 values < 50 nM), antibacterial effects (several with MIC values < 1 µg/mL) and to form stable ternary complexes with both wild-type and resistant mutants. Unexpectedly, crystal structures of a pair of individual enantiomers in the wild-type DHFR revealed that the single change in configuration of the stereocenter drove the selection of an alternative NADPH cofactor, with the minor α-anomer appearing with R-27. Remarkably, this cofactor switching becomes much more prevalent when the F98Y mutation is present. The observation of cofactor site plasticity leads to a postulate for the structural basis of TMP resistance in DHFR and also suggests design strategies that can be used to target these resistant enzymes. PMID:26098608

  19. Investigation of bone disease using isomerized and racemized fragments of type I collagen.

    PubMed

    Cloos, P A C; Fledelius, C; Christgau, S; Christiansen, C; Engsig, M; Delmas, P; Body, J-J; Garnero, P

    2003-01-01

    In the collagen type I C-telopeptide an aspartyl-glycine site within the sequence AHDGGR is susceptible to molecular rearrangement. In newly synthesized collagen this site is in the native form, denoted alpha L. During aging a spontaneous reaction occurs resulting in three age-modified forms: an isomerized form (beta L) a racemized form (alpha D), and an isomerized/racemized form (beta D). In this study, we measured the urinary excretion of the four forms of C-telopeptides (CTX) in healthy adults and in patients with bone diseases. Levels of all CTX forms were higher in healthy postmenopausal women (P<0.001) compared with premenopausal controls. Levels decreased within 3 days of bisphosphonate treatment indicating that all CTX forms reflect bone resorption. In hyperthyroidism, characterized by a generalized increased bone turnover, native (alpha L) and age-modified (beta L, alpha D and beta D) forms increased to a similar extent compared to controls, resulting in normal ratios between the alpha L and age-modified forms of CTX. Conversely, in Paget's disease and prostate cancer-induced bone metastases, conditions characterized by focal increased bone turnover, alpha L CTX levels were more elevated than those of age-related CTX forms, resulting in increased ratios between native and age-modified CTX. For example, the ratio alpha L/alpha D was increased 7-fold in Paget's disease (P<0.001) and 2-fold in prostate cancer-induced bone metastases (P<0.002). In conclusion, the study suggests that in conditions with a localized alteration in bone turnover the ratio between alpha L CTX and the age-modified forms is significantly elevated. This may provide a new diagnostic and monitoring tool for diseases such as metastatic bone cancer and Paget's disease. PMID:12384813

  20. An attempt to validate the ultra-accelerated microbar and the concrete performance test with the degree of AAR-induced damage observed in concrete structures

    SciTech Connect

    Leemann, Andreas; Merz, Christine

    2013-07-15

    There is little knowledge about the relation between AAR-induced damage observed in structures and the expansion potential obtained with accelerated tests. In this study, aggregates used in structures damaged by AAR were tested with the microbar test (MBT/AFNOR XP 18-594) and the concrete performance test (CPT/AFNOR P18-454). After the tests, the samples were examined using optical and scanning electron microscopy. Based on the results, the significance of the microbar test has to be examined very critically. The agreement of measured expansion, reacted rock types and the composition of the reaction products between the on-site concrete and the reproduced concrete subjected to the CPT clearly indicates that the reaction mechanisms in the structure and in the concrete performance test are comparable. As such, the concrete performance test seems to be an appropriate tool to test the potential reactivity of specific concrete mixtures.

  1. A one- and two-dimensional cross-section sensitivity and uncertainty path of the AARE (Advanced Analysis for Reactor Engineering) modular code system

    SciTech Connect

    Davidson, J.W.; Dudziak, D.J.; Higgs, C.E.; Stepanek, J.

    1988-01-01

    AARE, a code package to perform Advanced Analysis for Reactor Engineering, is a linked modular system for fission reactor core and shielding, as well as fusion blanket, analysis. Its cross-section sensitivity and uncertainty path presently includes the cross-section processing and reformatting code TRAMIX, cross-section homogenization and library reformatting code MIXIT, the 1-dimensional transport code ONEDANT, the 2-dimensional transport code TRISM, and the 1- and 2- dimensional cross-section sensitivity and uncertainty code SENSIBL. IN the present work, a short description of the whole AARE system is given, followed by a detailed description of the cross-section sensitivity and uncertainty path. 23 refs., 2 figs.

  2. Stereochemistry during aflatoxin biosynthesis: cyclase reaction in the conversion of versiconal to versicolorin B and racemization of versiconal hemiacetal acetate.

    PubMed Central

    Yabe, K; Hamasaki, T

    1993-01-01

    (1'R,2'S)-(-)-aflatoxins are produced from racemic versiconal hemiacetal acetate (VHA) through complicated pathways, including a metabolic grid involving VHA, versiconol acetate (VOAc), versiconol, and versiconal (VHOH), and a reaction sequence from VHOH to versicolorin A (VA) through (-)-versicolorin B (VB) [or (+/-)-versicolorin C] (K. Yabe, Y. Ando, and Y. Hamasaki, J. Gen. Microbiol. 137:2469-2475, 1991; K. Yabe, Y. Ando, and T. Hamasaki, Agric. Biol. Chem. 55:1907-1911, 1991). In this study, we examined stereochemical changes of substances formed during the conversion of VHA to VA by using chiral high-performance liquid chromatography. In cell-free experiments using the cytosol of Aspergillus parasiticus NIAH-26, both (2'S)- and (2'R)-VOAc enantiomers were formed at about a 1:2 ratio from racemic VHA in the presence of NADPH and dichlorvos (dimethyl 2,2-dichlorovinylphosphate). Also, the esterase activity catalyzing the conversion of VHA to VHOH or of VOAc to versiconol did not show the stereospecificity for the 2' carbon atom of VHA or VOAc. However, when racemic VHA or racemic VHOH was incubated with the cytosol, (1'R,2'S)-(-)-VB was formed exclusively. Furthermore, only (1'R,2'S)-(-)-VB, and not (1'S,2'R)-(+) antipode, served as a substrate for desaturase activity in the microsome fraction catalyzing the conversion of VB to VA. These results demonstrate that the stereoconfiguration of bis-furan moiety in aflatoxin molecules is determined by the cyclase enzyme catalyzing the reaction from VHOH to VB, and the (1'R,2'S)-(-) configuration was further confirmed by the subsequent desaturase reaction. Remarkably, we found nonenzymatic racemization in both the (2'R)- and (2'S)-VHA enantiomers, and it was dependent upon the temperature and alkaline conditions. PMID:8368837

  3. This NASA Dryden F/A-18 is participating in the Automated Aerial Refueling (AAR) project. F/A-18 (No

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA Dryden F/A-18 is participating in the Automated Aerial Refueling (AAR) project. F/A-18 (No. 847) is acting as an in-flight refueling tanker in the study to develop analytical models for an automated aerial refueling system for unmanned vehicles. A 300-gallon aerodynamic pod containing air-refueling equipment is seen beneath the fuselage. The hose and refueling basket are extended during an assessment of their dynamics on the F/A-18A.

  4. The optical nature of methylsuccinic acid in human urine

    NASA Technical Reports Server (NTRS)

    Zeitman, B.; Lawless, J. G.

    1975-01-01

    Methylsuccinic acid was isolated from human urine, derivatized as the di-S-(+)-2-butyl ester, and analyzed using a gas chromatographic system capable of separating the enantiomers of the derivative. The R-(+)-isomer was found to be present. Methylsuccinic acid is potentially important as a criterion for abiogenicity, having been obtained as a racemic mixture from sources known to be abiotic.

  5. Geochemical evolution of amino acids in dentine of Pleistocene bears.

    PubMed

    De Torres, T; Ortiz, J E; García, M J; Llamas, J F; Canoira, L; De La Morena, M A; Juliá, R

    2001-08-01

    A linear correlation was established between aspartic acid racemization ratio from cave bear dentine collagen and absolute dating. The high correlation coefficient obtained allowed age calculation through amino acid racemization. Aspartic acid and glutamic acid racemization kinetics have also been explored in dentine from a North American black bear (Ursus americanus Pallas). Three sample sets were prepared for kinetic heating experiments in nitrogen atmosphere: one water soaked, one with a water-saturated nitrogen atmosphere, and one without any moisture. It was possible to show that the presence of water is a factor controlling amino acid racemization rate. The aspartic acid in a heating experiment at 105 degrees C shows an "apparent kinetics reversal" which can be explained by a progressive hydrolysis of amino acid chains (proteins and polypeptides). Because of the low potential of collagen preservation over long periods of time, the apparent kinetics reversal phenomenon will not affect the dating of old material where no traces of collagen remain. An apparent kinetics reversal was not observed in glutamic acid, which racemizates more slowly. PMID:11466777

  6. A Multi-Enzymatic Cascade Reaction for the Stereoselective Production of γ-Oxyfunctionalyzed Amino Acids.

    PubMed

    Enoki, Junichi; Meisborn, Jaqueline; Müller, Ann-Christin; Kourist, Robert

    2016-01-01

    A stereoselective three-enzyme cascade for synthesis of diasteromerically pure γ-oxyfunctionalized α-amino acids was developed. By coupling a dynamic kinetic resolution (DKR) using an N-acylamino acid racemase (NAAAR) and an L-selective aminoacylase from Geobacillus thermoglucosidasius with a stereoselective isoleucine dioxygenase from Bacillus thuringiensis, diastereomerically pure oxidized amino acids were produced from racemic N-acetylamino acids. The three enzymes differed in their optimal temperature and pH-spectra. Their different metal cofactor dependencies led to inhibitory effects. Under optimized conditions, racemic N-acetylmethionine was quantitatively converted into L-methionine-(S)-sulfoxide with 97% yield and 95% de. The combination of these three different biocatalysts allowed the direct synthesis of diastereopure oxyfunctionalized amino acids from inexpensive racemic starting material. PMID:27092111

  7. A Multi-Enzymatic Cascade Reaction for the Stereoselective Production of γ-Oxyfunctionalyzed Amino Acids

    PubMed Central

    Enoki, Junichi; Meisborn, Jaqueline; Müller, Ann-Christin; Kourist, Robert

    2016-01-01

    A stereoselective three-enzyme cascade for synthesis of diasteromerically pure γ-oxyfunctionalized α-amino acids was developed. By coupling a dynamic kinetic resolution (DKR) using an N-acylamino acid racemase (NAAAR) and an L-selective aminoacylase from Geobacillus thermoglucosidasius with a stereoselective isoleucine dioxygenase from Bacillus thuringiensis, diastereomerically pure oxidized amino acids were produced from racemic N-acetylamino acids. The three enzymes differed in their optimal temperature and pH-spectra. Their different metal cofactor dependencies led to inhibitory effects. Under optimized conditions, racemic N-acetylmethionine was quantitatively converted into L-methionine-(S)-sulfoxide with 97% yield and 95% de. The combination of these three different biocatalysts allowed the direct synthesis of diastereopure oxyfunctionalized amino acids from inexpensive racemic starting material. PMID:27092111

  8. Non-cyclooxygenase prostaglandin synthesis in the sea whip coral, Plexaura homomalla: an 8(R)-lipoxygenase pathway leads to formation of an alpha-ketol and a Racemic prostanoid

    SciTech Connect

    Brash, A.R.; Baertschi, S.W.; Ingram, C.D.; Harris, T.M.

    1987-11-25

    Plexaura homomalla is a rich natural source of prostaglandins and recent evidence suggest the prostaglandin biosynthesis could occur through a lipoxygenase pathway. We have investigated the metabolism of arachidonic acid in homogenates and acetone powders of the fresh frozen coral. The biosynthesis of natural prostaglandins was not detected. However, we find a prominent 8(R)-lipoxygenase pathway leading to an alpha-ketol, characterized by high pressure liquid chromatography, gas chromatography-mass spectrometry, and NMR as 8-hydroxy, 9-keto-eicosa-5Z, 11Z, 14Z-trienoic acid, and a prostaglandin A-like cyclopentenone identified as 9-oxo-(8, 12-cis)-prosta-5Z, 10, 14Z-trienoic acid. These reactions appear analogous to the transformation of linolenic acid hydroperoxide by isomerase and cyclase of corn and flaxseed. From analysis of the absolute configurations of the coral products, and from additional stable isotope labeling experiments in H/sub 2//sup 18/O and D/sub 2/O, we deduce that both compounds arise via conversion of 8(R)-HPETE to an 8(R), 9-allene oxide, 8R,9-oxido-eicosa-5Z, 9, 11Z, 14Z-tetraenoic acid. This unstable intermediate undergoes hydrolysis to form the alpha-ketol or cyclization to give the cyclopentenone. Significantly, we find that the prostaglandin-like product is a racemic mixture of cis side chain enantiomers, pointing to its nonenzymatic origin from the allene oxide. The alpha-ketol is formed with partial racemization and inversion of configuration, also compatible with formation in a nonenzymatic reaction. We conclude that the isomerase and cyclase reactions may merely reflect nonenzymatic breakdown of the enzymatically formed allene oxide.

  9. Enantioselective assembly of amphipathic chiral polymer and racemic chiral small molecules during preparation of micro-scale polymer vesicles.

    PubMed

    Wang, Yingjue; Zhuang, Yiwei; Gao, Jiangang; Zou, Gang; Zhang, Qijin

    2016-03-14

    Enantioselective assembly is observed during preparation of vesicles from a solution mixture of an amphipathic block copolymer bearing pendent chiral l- or d-phenylalanine groups in hydrophobic segments and racemic chiral small molecules. Primary experimental results reveal that racemic chiral small molecules have been enantioselectively encapsulated into the hydrophobic shells of assembled vesicles with homochiral bilayer membrane structure, showing reverse CD signals compared with the original vesicles. A further study shows that the enantiomeric excess obtained through the enantioselective assembly is directly dependent on the molecular weight of the hydrophobic chiral chain segments, implying both the hydrophobic interaction and chirality are key points during the assembly of vesicles. Other factors, such as hydrogen-bonding interactions and π-π stacking interaction, are also found to be responsible for the enantioselective assembly phenomenon during the formation of the vesicles. PMID:26853976

  10. A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography

    SciTech Connect

    Bunker, Richard D.; Mandal, Kalyaneswar; Bashiri, Ghader; Chaston, Jessica J.; Pentelute, Bradley L.; Lott, J. Shaun; Kent, Stephen B. H.; Baker, Edward N.

    2015-04-07

    Racemic protein crystallography was used to determine the X-ray structure of the predicted Mycobacterium tuberculosis protein Rv1738, which had been completely recalcitrant to crystallization in its natural L-form. Native chemical ligation was used to synthesize both L-protein and D-protein enantiomers of Rv1738. Crystallization of the racemic {D-protein + L-protein} mixture was immediately successful. The resulting crystals diffracted to high resolution and also enabled facile structure determination because of the quantized phases of the data from centrosymmetric crystals. The X-ray structure of Rv1738 revealed striking similarity with bacterial hibernation factors, despite minimal sequence similarity. As a result, we predict that Rv1738, which is highly up-regulated in conditions that mimic the onset of persistence, helps trigger dormancy by association with the bacterial ribosome.

  11. From racemic precursors to fully stereocontrolled products: one-pot synthesis of chiral α-amino lactones and lactams.

    PubMed

    You, Zhi-Hao; Chen, Ying-Han; Liu, Yan-Kai

    2016-07-14

    Substituted racemic lactols or cyclic hemiaminals were directly used as nucleophiles in enamine-based asymmetric amination reactions to access enantioenriched α-amino lactones or lactams via a one-pot sequence. The desired products, which are very important building blocks in organic synthesis but difficult to be prepared in the optically enriched form, could be afforded with two stereogenic centers in high yields with excellent enantioselectivities. Moreover, starting from the racemic precursors and catalyzed by the enantiomeric pair of the catalyst, all possible stereoisomeric products were discretely provided only after simple column chromatography. Additionally, this protocol provides facile access to several novel bicyclic carbamates, and such drug-like heterocyclic compounds should be potentially useful in medicinal chemistry. PMID:27270561

  12. Kinetic Resolution of Racemic and Branched Monosubstituted Allylic Acetates by a Ruthenium-Catalyzed Regioselective Allylic Etherification.

    PubMed

    Shinozawa, Toru; Terasaki, Shou; Mizuno, Shota; Kawatsura, Motoi

    2016-07-01

    We demonstrated the kinetic resolution of racemic and branched monosubstituted allylic acetates by a ruthenium-catalyzed regioselective allylic etherification. The reaction was effectively catalyzed by the chiral ruthenium catalyst, which was generated by [RuCl2(p-cymene)]2 and (S,S)-iPr-pybox and a catalytic amount of TFA, and both the allylic etherification product and recovered allylic acetate were obtained as an enantiomerically enriched form with up to a 103 s value. PMID:27276556

  13. A novel control of enzymatic enantioselectivity through the racemic temperature influenced by reaction media.

    PubMed

    Jin, Xin; Liu, Bokai; Ni, Zhong; Wu, Qi; Lin, Xianfu

    2011-05-01

    The influence of reaction media on the racemic temperature (T(r)) in the lipase-catalyzed resolution of ketoprofen vinyl ester was investigated. An effective approach to the control of the enzymatic enantioselectivity and the prediction of the increasing tendency was developed based on the T(r) influenced by reaction media. The T(r) for the resolution catalyzed by Candida rugosa lipase (CRL) was found at 29 °C in aqueous and S-ketoprofen was obtained predominantly at 40 °C. However, CRL showed R-selectivity at 40 °C in diisopropyl ether because the T(r) was changed to 56 °C. CRL, lipase from AYS Amano(®) and Mucor javanicus lipase were further applied for the investigation of the enzymatic enantioselectivity in dioxane, DIPE, isooctane and their mixed media with water. The effects of the reaction medium on T(r) could be related to the solvent hydrophobicity, the lipase conformational flexibility and the interaction between the enantiomers and the lipase. PMID:22113016

  14. Inhalation of racemic epinephrine in children with asthma. Dose-response relation and comparison with salbutamol.

    PubMed

    Kjellman, B; Tollig, H; Wettrell, G

    1980-10-01

    In this study the effects of nebulized racemic epinephrine (Micronephrine) were investigated in children with asthma. The drug was inhaled by a compressor nebulizer with a plastic mask. In the first part of the study it is shown that nebulized Micronephrine has a dose-dependent bronchodilatory effect. In the second part the effect is compared with that of nebulized salbutamol in 10 children (7-16 years of age) with bronchial asthma. The highest dose used in the dose-response trials (=0.9 mg Micronephrine/kg body-weight) was compared with 0.15 mg salbutamol/kg body-weight, which is the dose commonly used in Sweden. There was no significant difference between the drugs as regards increase of forced expiratory volume in 1 sec or duration of the increase. There was a small but significant increase in systolic blood pressure, measured 5 min after the inhalation of Micronephrine but no significant change in diastolic pressure or heart rate. Four children complained of temporary sore throat after the inhalation. PMID:7468946

  15. Chiral-phase high-performance liquid chromatography of rotenoid racemates

    USGS Publications Warehouse

    Abidi, S.L.

    1987-01-01

    The high-performance liquid chromatograhic (HPLC) behavior of parent rotenoids (type I) and the hydroxyl-analogues (type II) on three different chiral stationary phases (CSPs) was studied. Separations of optical isomers were achieved in various degrees depending largely upon the rotenoidal structures and the CSP types employed. Enantiomers of all but elliptone compounds were separable on β-cyclodextrin-bonded silica (CDS). Without exception, the 12a-hydroxyrotenoid antipodes were resolved on Pirkle's phenylglycine-bonded silica (PGS) despite unsuccessful attenmpts to resolve the type I rotenoidal racemates. Conversely, optical resolution of the latter rotenoids was accomplished by using a helical polytriphenylmethylacrylate-coated silica (TPS) column and the observed separation factors (α values) ranged from 1.14 to 1.90. The results from HPLC of type II rotenoids on TPS (α = 1.00–1.63) suggested that variations in E-ring structures had profound influence on the resolution outcome. Conjugated double bonds on the E-ring and the desisopropylation of the five-membered E-ring ot type II rotenoids appeared to be important structural features for chiral recognition involving the TPS substrate. In both reversed-phase (CDS) and normal-pahse (PGS and TPS) HPLC modes, the less polar enantiomers were the 6aβ,12aβ-rotenoids as observed in most cases, though this relationship was reversed in the cases of deguelin and hydroxyelliptone probably due to conformational effects of rotenoidal ring systems.

  16. Racemization of alanine by the alanine racemases from Salmonella typhimurium and Bacillus stearothermophilus: energetic reaction profiles

    SciTech Connect

    Faraci, W.S.; Walsh, C.T.

    1988-05-03

    Alanine racemases are bacterial pyridoxal 5'-phosphate (PLP) dependent enzymes providing D-alanine as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall. Two isozymic alanine racemases, encoded by the dadB gene and the alr gene, from the Gram-negative mesophilic Salmonella typhimurium and one from the Gram-positive thermophilic Bacillus stearothermophilus have been examined for the racemization mechanism. Substrate deuterium isotope effects and solvent deuterium isotope effects have been measured in both L ..-->.. D and D..-->.. L directions for all three enzymes to assess the degree to which abstraction of the ..cap alpha..-proton or protonation of substrate PLP carbanion is limiting in catalysis. Additionally, experiments measuring internal return of ..cap alpha..-/sup 3/H from substrate to product and solvent exchange/substrate conversion experiments in /sup 3/H/sub 2/O have been used with each enzyme to examine the partitioning of substrate PLP carbanion intermediates and to obtain the relative heights of kinetically significant energy barriers in alanine racemase catalysis.

  17. Racemic salbutamol and levosalbutamol in mild persistent asthma: A comparative study of efficacy and safety

    PubMed Central

    Maiti, Rituparna; Prasad, Chenimilla Nagender; Jaida, Jyothirmai; Mukkisa, Sruthi; Koyagura, Narendar; Palani, Anuradha

    2011-01-01

    Aim: The effect of monotherapy with racemic salbutamol and levosalbutamol on symptoms, quality of life, and pulmonary function has been assessed and compared in mild persistent asthma. Materials and Methods: A randomized, open, parallel clinical study was conducted on 60 patients of mild persistent asthma. After baseline assessments, salbutamol was prescribed to 30 patients and levosalbutamol to another 30 for 4 weeks. The efficacy variables were change in asthma symptom scoring, pulmonary function test, and Mini Asthma Quality of Life Questionnaire (MiniAQLQ) scoring. At follow-up, the patients were re-evaluated and analyzed by statistical tools. Results: Shortness of breath (P<0.001), chest tightness (P=0.033), wheeze (P=0.01), cough (P=0.024), and overall asthma symptom score (P<0.001) were significantly decreased in the levosalbutamol group in comparison to the salbutamol group. Results of MiniAQLQ revealed that improvement in symptoms (P=0.018), activity limitations (P=0.03), environmental stimuli (P=0.013)-related scoring and overall MiniAQLQ scoring (P<0.001) was statistically significant in the levosalbutamol group. Percentage reversibility of forced expiratory volume at one second (P=0.034), forced vital capacity (P=0.029), peak expiratory flow rate (P=0.0003) was found to be superior in the levosalbutamol group. Conclusion: Levosalbutamol was found to be superior compared to recemic salbutamol in mild persistent asthma. PMID:22144765

  18. Levalbuterol compared with racemic albuterol in the treatment of acute asthma: results of a pilot study.

    PubMed

    Nowak, Richard M; Emerman, Charles L; Schaefer, Kendyl; Disantostefano, Rachel L; Vaickus, Louis; Roach, James M

    2004-01-01

    This was a prospective, open-label, nonrandomized pilot study to evaluate efficacy and tolerability of levalbuterol (LEV) in acute asthma. Asthmatics (forced expiratory volume in 1 second [FEV1], 20-55% predicted) were sequentially enrolled into cohorts of 12 to 14 and received 0.63, 1.25, 2.5, 3.75, or 5.0 mg LEV or 2.5 or 5.0 mg racemic albuterol (RAC) every 20 minutes x 3. After the first dose, FEV1 changes were 56% (0.6 L) for 1.25 mg LEV and 6% (0.07 L) and 14% (0.21 L) for 2.5 and 5 mg RAC respectively. After three doses, FEV1 changes were 74% (0.9 L), 39% (0.5 L), and 37% (0.6 L) for 1.25 mg, LEV 2.5 mg, RAC and 0.63 mg LEV respectively. LEV doses greater than 1.25 mg did not further improve bronchodilation. Baseline plasma (S)-albuterol levels were negatively correlated with baseline FEV1 (R = - 0.3, P = .004) and percent change in FEV1 (R = -0.3, P = .006). LEV at a dose of 1.25 mg produced effective bronchodilation that was greater than both RAC doses. The negative correlation between (S)-albuterol levels and FEV1 could suggest a deleterious effect of (S)-albuterol. Larger comparative studies are warranted. PMID:14724875

  19. Changes in heart rate associated with nebulized racemic albuterol and levalbuterol in intensive care patients.

    PubMed

    Lam, Sum; Chen, Julie

    2003-10-01

    The effects of equipotent doses of racemic albuterol and levalbuterol on heart rate (HR) in intensive care patients with and without baseline tachycardia were studied. Patients were included if they were hemodynamically stable and required bronchodilator therapy every four hours; patients were excluded if they were maintained on a beta-blocker. Four hours after the most recent bronchodilator treatment, each patient was randomized to receive at least two consecutive doses of albuterol 2.5 mg or levalbuterol 1.25 mg four hours apart via nebulization. HR was recorded at the end of the second dose and 5, 10, 15, 30, 60, 90, 120, 180, and 240 minutes after treatment. Twenty intensive care patients, including 10 with baseline tachycardia and 10 without baseline tachycardia, were enrolled. In patients with baseline tachycardia, the mean largest HR increase was 1.4 beats/min (1.3%) with albuterol and 2.0 beats/min (2.1%) with levalbuterol (both increases were not significant). In patients without baseline tachycardia, the mean largest HR increase was 4.4 beats/min (6.7%) with albuterol (p = 0.04) and 3.6 beats/min (5.0%) with levalbuterol (p = 0.03). Short-term use of nebulized albuterol and levalbuterol was associated with similar changes in HR in intensive care patients with or without baseline tachycardia. PMID:14531242

  20. Tolerability and effectiveness of (S)-amlodipine compared with racemic amlodipine in hypertension: A systematic review and meta-analysis

    PubMed Central

    Liu, Fang; Qiu, Meng; Zhai, Suo-Di

    2010-01-01

    Background: Amlodipine is a calcium channel blocker prescribed for the management of angina and hypertension. As a racemic mixture, amlodipine contains (R)- and (S)-amlodipine isomers, but only (S)-amlodipine as the active moiety possesses therapeutic activity. Based on pharmacologic research, it remains uncertain if (S)-amlodipine alone has similar efficacy and fewer associated adverse events (AEs) compared with the racemic mixtures. Objective: The aim of this systematic review and meta-analysis was to determine the effectiveness and tolerability of (S)-amlodipine compared with that of racemic amlodipine. Methods: A systematic literature search was performed using MEDLINE (1966–2009), EMBASE (1966–2009), the Cochrane Central Register of Controlled Trials (issue 3, 2009), the Chinese Biomedical Database (1978–2009), and the China National Knowledge Internet (1980–2009). All randomized controlled trials (RCTs) comparing (S)-amlodipine 2.5 mg and racemic amlodipine 5.0 mg in the treatment of hypertension were included in the review. The outcome measures to be collected were cardiovascular events, systolic blood pressure (SBP), diastolic BP (DBP), and AEs. Quality assessments of clinical trials were conducted using a modified Jadad Scale, with trials being rated as low quality (score 0–3) or high quality (score 4–7). Meta-analysis of the included studies was performed using RevMan software. Results: Of the 229 references identified, 214 were excluded after screening the titles, abstracts, or full texts. Fifteen RCTs were included, of which 13 were in Chinese and 2 in English. Based on the Jadad Scale score, 3 of the RCTs were classified as high quality (score 5 or 6) and the remaining 12 as low quality (score 1–3). None of the trials evaluated cardiovascular events beyond 40 weeks. Meta-analysis of the 15 trials indicated that (S)-amlodipine was not significantly different from racemic amlodipine in the effect on BP. When only high-quality studies were

  1. D-amino acid formation in sterilized alkali-treated olives.

    PubMed

    Casado, Francisco Javier; Sánchez, Antonio Higinio; Rejano, Luis; Montaño, Alfredo

    2007-05-01

    The occurrence of d-amino acids in commercial ripe olives, a well-known sterilized alkali-treated product, was investigated by high-performance liquid chromatography (HPLC) with precolumn automatic derivatization. Absolute amounts of D-amino acids were in total 18.6-38.2 mg/100 g edible portion. The major D-amino acids were D-aspartic acid, D-glutamic acid, D-serine, and D-leucine. Furthermore, to evaluate the effects of sterilization time and olive pH on amino acid racemization, a simulated processing of green ripe olives was carried out. Serine (both free and bound form) was the most-racemized amino acid after heat treatment. Sterilization (15-35 min at 121 degrees C) increased the racemization values of both free and protein-bound amino acids, although in case of protein-bound phenylalanine the increase was not statistically significant. With an increase of pH from 8 to 10 units, the racemization values of all amino acids increased significantly, except for free forms of aspartic and glutamic acids. In general, the effects of the sterilization time and olive pH on total concentration (L + D enantiomers) of each amino acid were also significant. PMID:17407322

  2. Difference in the dynamic properties of chiral and racemic crystals of serine studied by Raman spectroscopy at 3-295 K.

    PubMed

    Kolesov, B A; Boldyreva, E V

    2007-12-27

    Single-crystal polarized Raman spectra (60-4000 cm(-1) at 3 < or = T < or = 295 K) were measured for chiral L- and racemic DL-serine, alpha-amino-beta-hydroxypropionic acid, (NH3)+CH(CH2OH)(COO)-. The Raman spectra of dl-serine do not show any striking changes with temperature or on storage. In contrast to that, the dynamical properties of L-serine change at about 140 K. These changes can be interpreted as the reorientation of the side chain -CH2OH fragments of the zwitterions with respect to the backbone C-C bonds, resulting in the positional disorder of the O-H...O intermolecular H-bonds. The redistribution in the intensities of the Raman spectra of the crystals of L-serine stored for a long time (about a year) indicates the changes in the orientation of the molecular fragments in the direction normal to the axes of the head-to-tail chains. The difference in the thermodynamic functions of L- and DL-serine reported previously [Drebushchak, V. A.; Kovalevskaya, Yu. A.; Paukov, I. E.; Boldyreva, E. V. J. Therm. Anal. Calorim. 2007, 89 (2), 649-654] is explained by the difference in the spectra of external vibrations of the crystals. PMID:18052147

  3. Conventional Chiralpak ID vs. capillary Chiralpak ID-3 amylose tris-(3-chlorophenylcarbamate)-based chiral stationary phase columns for the enantioselective HPLC separation of pharmaceutical racemates.

    PubMed

    Ahmed, Marwa; Gwairgi, Marina; Ghanem, Ashraf

    2014-11-01

    A comparative enantioselective analysis using immobilized amylose tris-(3-chlorophenylcarbamate) as chiral stationary phase in conventional high-performance liquid chromatography (HPLC) with Chiralpak ID (4.6 mm ID × 250 mm, 5 µm silica gel) and micro-HPLC with Chiralpak ID-3 (0.30 mm ID × 150 mm, 3 µm silica gel) was conducted. Pharmaceutical racemates of 12 pharmacological classes, namely, α- and β-blockers, anti-inflammatory drugs, antifungal drugs, dopamine antagonists, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, diuretics, antihistaminics, anticancer drugs, and antiarrhythmic drugs were screened under normal phase conditions. The effect of an organic modifier on the analyte retentions and enantiomer recognition was investigated. Baseline separation was achieved for 1-acenaphthenol, carprofen, celiprolol, cizolirtine carbinol, miconazole, tebuconazole, 4-hydroxy-3-methoxymandelic acid, 1-indanol, 1-(2-chlorophenyl)ethanol, 1-phenyl-2-propanol, flavanone, 6-hydroxyflavanone, 4-bromogluthethimide, and pentobarbital on the 4.6 mm ID packed with a 5 µm silica column using conventional HPLC. Nonetheless, baseline separation was achieved for aminoglutethimide, naftopidil, and thalidomide on the 0.3 mm ID packed with a 3 µm silica capillary column. PMID:25271972

  4. A mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-dependent transcriptional program controls activation of the early growth response 1 (EGR1) gene during amino acid limitation.

    PubMed

    Shan, Jixiu; Balasubramanian, Mukundh N; Donelan, William; Fu, Lingchen; Hayner, Jaclyn; Lopez, Maria-Cecilia; Baker, Henry V; Kilberg, Michael S

    2014-08-29

    Amino acid (AA) limitation in mammalian cells triggers a collection of signaling cascades jointly referred to as the AA response (AAR). In human HepG2 hepatocellular carcinoma, the early growth response 1 (EGR1) gene was induced by either AA deprivation or endoplasmic reticulum stress. AAR-dependent EGR1 activation was discovered to be independent of the well characterized GCN2-ATF4 pathway and instead dependent on MEK-ERK signaling, one of the MAPK pathways. ChIP showed that constitutively bound ELK1 at the EGR1 proximal promoter region was phosphorylated after AAR activation. Increased p-ELK1 binding was associated with increased de novo recruitment of RNA polymerase II to the EGR1 promoter. EGR1 transcription was not induced in HEK293T cells lacking endogenous MEK activity, but overexpression of exogenous constitutively active MEK in HEK293T cells resulted in increased basal and AAR-induced EGR1 expression. ChIP analysis of the human vascular endothelial growth factor A (VEGF-A) gene, a known EGR1-responsive gene, revealed moderate increases in AAR-induced EGR1 binding within the proximal promoter and highly inducible binding to a site within the first intron. Collectively, these data document a novel AA-activated MEK-ERK-ELK1 signaling mechanism. PMID:25028509

  5. A Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase (MEK)-dependent Transcriptional Program Controls Activation of the Early Growth Response 1 (EGR1) Gene during Amino Acid Limitation*

    PubMed Central

    Shan, Jixiu; Balasubramanian, Mukundh N.; Donelan, William; Fu, Lingchen; Hayner, Jaclyn; Lopez, Maria-Cecilia; Baker, Henry V.; Kilberg, Michael S.

    2014-01-01

    Amino acid (AA) limitation in mammalian cells triggers a collection of signaling cascades jointly referred to as the AA response (AAR). In human HepG2 hepatocellular carcinoma, the early growth response 1 (EGR1) gene was induced by either AA deprivation or endoplasmic reticulum stress. AAR-dependent EGR1 activation was discovered to be independent of the well characterized GCN2-ATF4 pathway and instead dependent on MEK-ERK signaling, one of the MAPK pathways. ChIP showed that constitutively bound ELK1 at the EGR1 proximal promoter region was phosphorylated after AAR activation. Increased p-ELK1 binding was associated with increased de novo recruitment of RNA polymerase II to the EGR1 promoter. EGR1 transcription was not induced in HEK293T cells lacking endogenous MEK activity, but overexpression of exogenous constitutively active MEK in HEK293T cells resulted in increased basal and AAR-induced EGR1 expression. ChIP analysis of the human vascular endothelial growth factor A (VEGF-A) gene, a known EGR1-responsive gene, revealed moderate increases in AAR-induced EGR1 binding within the proximal promoter and highly inducible binding to a site within the first intron. Collectively, these data document a novel AA-activated MEK-ERK-ELK1 signaling mechanism. PMID:25028509

  6. Regio- and stereoselective isomerization of hexabromocyclododecanes (HBCDs): kinetics and mechanism of beta-HBCD racemization.

    PubMed

    Heeb, Norbert V; Schweizer, W Bernd; Mattrel, Peter; Haag, Regula; Kohler, Martin; Schmid, Peter; Zennegg, Markus; Wolfensberger, Max

    2008-04-01

    Hexabromocyclododecanes (HBCDs) are high production volume chemicals currently produced in quantities exceeding 20000ty(-1). They are used as flame retardants for plastics and textiles. HBCDs are thermally labile compounds, rapidly decomposing at temperatures above 250 degrees C to form bromine radicals, which scavenge other radicals formed during pyrolysis. But certain HBCD stereoisomers must reach the environment without decomposition, because their levels in soils, sediments, and biota are increasing worldwide. The fate of individual HBCD stereoisomers during production, product use, disposal, and transformation in the environment remains unclear. Herein we report on the thermally induced, highly selective isomerization of (+) and (-)beta-HBCD. Regio- and stereoselective migration of only two of the six bromine atoms resulted in the racemization of both beta-HBCDs. First order rate constants (k(rac)) increased from 0.005, 0.011, 0.021, to 0.055min(-1) at 130, 140, 150, and 160 degrees C, corresponding to half life times tau(1/2) of 143, 63, 29, and 14min, respectively. From the deduced kinetic model, we conclude that any thermal treatment of enantiomerically enriched beta-HBCDs in the range of 100-160 degrees C will result in a loss of most optical activity within few hours. The simultaneous inversion of two asymmetric centers occurred with perfect stereocontrol. Selectively, vicinal dibromides with the RR- and the SS-configurations migrated at these temperatures. An intramolecular reaction mechanism with a four-center transition state is postulated, based on the obtained stereoisomer pattern and the observed reaction kinetics. Crystal structure analysis revealed that all vicinal dibromides in beta-HBCDs prefer synclinal (gauche) conformations. However, an antiperiplanar (staggered) conformation is assumed to facilitate the concerted 1.2-shifts of both bromine atoms, resulting in an inversion of both neighboring carbon atoms. First experiments with other HBCD

  7. The effects of racemic albuterol versus levalbuterol in very low birth weight infants.

    PubMed

    Mhanna, Maroun J; Patel, Jigisha S; Patel, Swati; Cohn, Robert

    2009-08-01

    Bronchodilators have been used in premature infants. Levalbuterol (LEV) an R-isomer of Albuterol has fewer hemodynamic side effects than Racemic Albuterol (RAC) in adults and children. In a retrospective study we sought to investigate the effects of LEV (0.31 mg) versus RAC (1.25 mg) in very low-birth weight infants (VLBW) who were treated with a beta-2 agonist for > or =2 weeks. Medical records (between January 2001 and December 2006) were reviewed for patients' demographics, medications use, hemodynamic and respiratory parameters, hypokalemia and hyperglycemia. Among 811 VLBW infants who were admitted to our NICU, 16 infants received RAC and 31 infants received LEV for > or =2 weeks. Infants who received RAC were younger, smaller, and received less Ipratropium Bromide (IB) than infants who received LEV [26.1 +/- 1.2 weeks vs. 28.1 +/- 3.7 weeks (P = 0.01), 817 +/- 211 g vs. 1,127 +/- 589 g (P = 0.01) and 2/16 (12%) vs. 15/31 (48%; P = 0.01); respectively]. In infants treated exclusively with RAC or LEV without IB, mean arterial blood pressures were lower in the RAC (n = 14) than the LEV group (n = 16, P = 0.05 by general linear model with repeated measures); however there were no differences in daily heart rates, oxygen supplementations, oxygen saturations, or respiratory rates. Also there were no differences between the two groups in hypokalemia or hyperglycemia. We conclude that LEV at a dose of 0.31 mg might have an indication in VLBW infants who are at risk for hemodynamic instability. PMID:19598281

  8. [Nonsteroidal anti-inflammatory agents. XIII. 4-Cyclohexylphenylhydroxyalkanoic acids].

    PubMed

    Guarnieri, A; Burnelli, S; Varoli, L; Fabbri, G; Scapini, G; Sarret, M; Bertoli, D

    1983-09-01

    The preparation of some homologues of 2-(4-cyclohexylphenyl)-3-hydroxypropionic acid, the separation of the diastereomeric race-mates, their attribution to erythro and threo series, and the optical resolution of the enantiomers are described. The optical antipodes were screened for acute toxicity, as well as for antiinflammatory and analgesic activity. PMID:6641934

  9. Experiments on the origins of optical activity. [in amino acids

    NASA Technical Reports Server (NTRS)

    Bonner, W. A.; Flores, J. J.

    1975-01-01

    An investigation was conducted concerning the asymmetric adsorption of phenylalanine enantiomers by kaolin. No preferential adsorption of either phenylalanine enantiomer could be detected and there was no resolution of the racemic phenylalanine by kaolin. The attempted asymmetric polymerization of aspartic acid by kaolin is also discussed along with a strontium-90 bremsstrahlung radiolysis of leucine.

  10. Synthesis and evaluation of the racemate and individual enantiomers of C-11 labeled methylphenidate as radioligands for the presynaptic dopaminergic neuron

    SciTech Connect

    Ding, Y.S.; Fowler, J.S.; Volkow, N.D.

    1994-05-01

    Methylphenidate (MP, ritalin) is a psychostimulant drug widely used to treat attention deficit hyperactivity disorder and narcolepsy. Its therapeutic properties are attributed to inhibition of the dopamine (DA) transporter enhancing synaptic DA. MP has two chiral centers and is marketed as the dl-threo racemic form. However, its pharmacological activity is believed due solely to the d-enantiomer. We have synthesized [{sup 11}C]d,l-threo-methylphenidate ([{sup 11}C]MP) in order to examine its pharmacokinetics in vivo and to examine its suitability as a radioligand for PET studies of the presynaptic DA neuron. [{sup 11}C]MP was prepared by O-{sup 11}C-alkylation of a protected derivative of ritalinic acid with labeled methyl iodide. Serial studies at baseline and after treatment with methylphenidate (0.5 mg/kg, 20 min prior); GBR 12909 (1.5 mg/kg; 30 min prior); tomoxetine (1.5 mg/kg, 20 min prior) and citalopram (2.0 mg/kg, 30 min prior) were performed to assess non-specific binding and binding to the DA, norepinephrine and serotonin transporters respectively. Only MP and GBR 12909 changed the SR/CB distribution volume ratio (decrease of 38 and 37% respectively) demonstrating selectivity for DA transporters over other monoamine transporters. We then pursued the synthesis of enantiomerically pure C-{sup 11} labeled d- and l-MP by using enantiomerically pure protected d- and l-ritalinic acids as precursors. A striking difference in SR/CB ratio (3.3 and 1.1 for d- and l-respectively at 1 hr. after i.v. injections) strongly suggests that the pharmacological specificity of MP resides entirely in the d-isomer and the binding of l-isomer was mostly non-specific. Further evaluations are underway. Radioligand reversibility, selectivity and the fact that MP is an approved drug are advantages of using [{sup 11}C]MP.

  11. Copper-catalysed asymmetric allylic alkylation of alkylzirconocenes to racemic 3,6-dihydro-2H-pyrans

    PubMed Central

    Rideau, Emeline

    2015-01-01

    Summary Asymmetric allylic alkylation is a powerful reaction that allows the enantioselective formation of C–C bonds. Here we describe the asymmetric alkylation of alkylzirconium species to racemic 3,6-dihydro-2H-pyrans. Two systems were examined: 3-chloro-3,6-dihydro-2H-pyran using linear optimization (45–93% ee, up to 33% yield, 5 examples) and 3,6-dihydro-2H-pyran-3-yl diethyl phosphate with the assistance of a design of experiments statistical approach (83% ee, 12% yield). 1H NMR spectroscopy was used to gain insight into the reaction mechanisms. PMID:26734091

  12. Crystal structure of racemic cis-2-amino-1,2-di­phenyl­ethanol (ADE)

    PubMed Central

    Fujii, Isao

    2015-01-01

    In the title racemic compound, C14H15NO, the hy­droxy and amino groups form a bent tweezer-like motif towards the phenyl groups. In the crystal, enanti­omers aggregate with each other and are linked by O—H⋯N hydrogen bonds, forming chiral 21-helical columnar structures from C(5) chains along the b-axis direction. Left- and right-handed 21 helices are formed from (1S,2R)-2-amino-1,2-di­phenyl­ethanol and (1R,2S)-2-amino-1,2-di­phenyl­ethanol, respectively. PMID:26870424

  13. Differential Influences of Ethanol on Early Exposure to Racemic Methylphenidate Compared with Dexmethylphenidate in Humans

    PubMed Central

    Straughn, Arthur B.; Reeves, Owen T.; Bernstein, Hilary; Bell, Guinevere H.; Anderson, Erica R.; Malcolm, Robert J.

    2013-01-01

    Enantioselective hydrolysis of oral racemic methylphenidate (dl-MPH) by carboxylesterase 1 (CES1) limits the absolute bioavailability of the pharmacologically active d-MPH isomer to approximately 30% and that of the inactive l-MPH to only 1–2%. Coadministration of dl-MPH with ethanol results in elevated d-MPH plasma concentrations accompanied by CES1-mediated enantioselective transesterification of l-MPH to l-ethylphenidate (EPH). The present study tested the hypothesis that administration of the pure isomer dexmethylphenidate (d-MPH) will overcome the influence of ethanol on d-MPH absorption by eliminating competitive CES1-mediated presystemic metabolism of l-MPH to l-EPH. Twenty-four healthy volunteers received dl-MPH (0.3 mg/kg) or d-MPH (0.15 mg/kg), with or without ethanol (0.6 g/kg). During the absorption phase of dl-MPH, concomitant ethanol significantly elevated d-MPH plasma concentrations (44–99%; P < 0.005). Furthermore, immediately following the ethanol drink the subjective effects of “high,” “good,” “like,” “stimulated,” and overall “effect” were significantly potentiated (P ≤ 0.01). Plasma l-EPH concentrations exceeded those of l-MPH. Ethanol combined with pure d-MPH did not elevate plasma d-MPH concentrations during the absorption phase, and the ethanol-induced potentiation of subjective effects was delayed relative to dl-MPH-ethanol. These findings are consistent with l-MPH competitively inhibiting presystemic CES1 metabolism of d-MPH. Ethanol increased the d-MPH area under the curve (AUC)0-inf by 21% following dl-MPH (P < 0.001) and 14% for d-MPH (P = 0.001). In men receiving d-MPH-ethanol, the d-MPH absorption partial AUC0.5–2 hours was 2.1 times greater and the time to maximum concentration (Tmax) occurred 1.1 hours earlier than in women, consistent with an increased rate of d-MPH absorption reducing hepatic extraction. More rapid absorption of d-MPH carries implications for increased abuse liability. PMID:23104969

  14. Influence of formulation on the pharmacokinetics and bioavailability of racemic ketoprofen in horses.

    PubMed

    Landoni, M F; Lees, P

    1995-12-01

    The bioavailability of S(+) and R(-) ketoprofen (KTP) in six horses was investigated after oral administration of the racemic (rac) mixture. Two oral formulations were studied, an oil-based paste containing micronised rac-KTP and powder from the same source in hard gelatin capsules, each at a dose rate of 2.2 mg/kg. For the oil-based paste two feeding schedules were used; horses were either allowed free access to food or access to food was restricted for 4 h before and 5 h after dosing. The drug in hard gelatin capsules was administered to horses with restricted access to food. After intravenous administration of rac-KTP, S(+) enantiomer concentrations exceeded those of the R(-) enantiomer. For S(+) and R(-)KTP, respectively, pharmacokinetic parameters were, t1/2 beta 0.99 +/- 0.14 h, 0.70 +/- 0.13 h; ClB 0.56 +/- 0.09, 0.92 +/- 0.20 L/h/kg; Vd(ss) 0.53 +/- 0.11, 0.61 +/- 0.10 L/kg. Following oral administration of rac-KTP as the oil-based paste to horses with free access to food, there were no detectable concentrations in plasma in three animals at any sampling time, while a fourth animal showed very low concentrations at two sampling times only. In the two remaining horses very low but detectable concentrations were present for 5 h. In the horses with restricted access to food, rac-KTP paste administration produced higher concentrations in plasma. However, bioavailability was very low, 2.67 +/- 0.43 and 5.75 +/- 1.48% for R(-) and S(+)KTP, respectively. When administered as pure drug substance in hard gelatin capsules, absorption of KTP was fairly rapid, but incomplete. Bioavailability was 50.55 +/- 10.95 and 54.17 +/- 9.9% for R(-) and S(+)KTP, respectively. This study demonstrates that rac-KTP had a modest bioavailability when administered as a micronised powder in hard gelatin capsules to horses with restricted access to food. When powder from the same source was administered as an oil-based paste, it was for practical purposes not bioavailable, regardless on

  15. Differential influences of ethanol on early exposure to racemic methylphenidate compared with dexmethylphenidate in humans.

    PubMed

    Patrick, Kennerly S; Straughn, Arthur B; Reeves, Owen T; Bernstein, Hilary; Bell, Guinevere H; Anderson, Erica R; Malcolm, Robert J

    2013-01-01

    Enantioselective hydrolysis of oral racemic methylphenidate (dl-MPH) by carboxylesterase 1 (CES1) limits the absolute bioavailability of the pharmacologically active d-MPH isomer to approximately 30% and that of the inactive l-MPH to only 1-2%. Coadministration of dl-MPH with ethanol results in elevated d-MPH plasma concentrations accompanied by CES1-mediated enantioselective transesterification of l-MPH to l-ethylphenidate (EPH). The present study tested the hypothesis that administration of the pure isomer dexmethylphenidate (d-MPH) will overcome the influence of ethanol on d-MPH absorption by eliminating competitive CES1-mediated presystemic metabolism of l-MPH to l-EPH. Twenty-four healthy volunteers received dl-MPH (0.3 mg/kg) or d-MPH (0.15 mg/kg), with or without ethanol (0.6 g/kg). During the absorption phase of dl-MPH, concomitant ethanol significantly elevated d-MPH plasma concentrations (44-99%; P < 0.005). Furthermore, immediately following the ethanol drink the subjective effects of "high," "good," "like," "stimulated," and overall "effect" were significantly potentiated (P ≤ 0.01). Plasma l-EPH concentrations exceeded those of l-MPH. Ethanol combined with pure d-MPH did not elevate plasma d-MPH concentrations during the absorption phase, and the ethanol-induced potentiation of subjective effects was delayed relative to dl-MPH-ethanol. These findings are consistent with l-MPH competitively inhibiting presystemic CES1 metabolism of d-MPH. Ethanol increased the d-MPH area under the curve (AUC)(0-inf) by 21% following dl-MPH (P < 0.001) and 14% for d-MPH (P = 0.001). In men receiving d-MPH-ethanol, the d-MPH absorption partial AUC(0.5-2 hours) was 2.1 times greater and the time to maximum concentration (T(max)) occurred 1.1 hours earlier than in women, consistent with an increased rate of d-MPH absorption reducing hepatic extraction. More rapid absorption of d-MPH carries implications for increased abuse liability. PMID:23104969

  16. Racemic ketamine in adult head injury patients: use in endotracheal suctioning

    PubMed Central

    2013-01-01

    Introduction Endotracheal suctioning (ETS) is essential for patient care in an ICU but may represent a cause of cerebral secondary injury. Ketamine has been historically contraindicated for its use in head injury patients, since an increase of intracranial pressure (ICP) was reported; nevertheless, its use was recently suggested in neurosurgical patients. In this prospective observational study we investigated the effect of ETS on ICP, cerebral perfusion pressure (CPP), jugular oxygen saturation (SjO2) and cerebral blood flow velocity (mVMCA) before and after the administration of ketamine. Methods In the control phase, ETS was performed on patients sedated with propofol and remifentanil in continuous infusion. If a cough was present, patients were assigned to the intervention phase, and 100 γ/kg/min of racemic ketamine for 10 minutes was added before ETS. Results In the control group ETS stimulated the cough reflex, with a median cough score of 2 (interquartile range (IQR) 1 to 2). Furthermore, it caused an increase in mean arterial pressure (MAP) (from 89.0 ± 11.6 to 96.4 ± 13.1 mmHg; P <0.001), ICP (from 11.0 ± 6.7 to 18.5 ± 8.9 mmHg; P <0.001), SjO2 (from 82.3 ± 7.5 to 89.1 ± 5.4; P = 0.01) and mVMCA (from 76.8 ± 20.4 to 90.2 ± 30.2 cm/sec; P = 0.04). CPP did not vary with ETS. In the intervention group, no significant variation of MAP, CPP, mVMCA, and SjO2 were observed in any step; after ETS, ICP increased if compared with baseline (15.1 ± 9.4 vs. 11.0 ± 6.4 mmHg; P <0.05). Cough score was significantly reduced in comparison with controls (P <0.0001). Conclusions Ketamine did not induce any significant variation in cerebral and systemic parameters. After ETS, it maintained cerebral hemodynamics without changes in CPP, mVMCA and SjO2, and prevented cough reflex. Nevertheless, ketamine was not completely effective when used to control ICP increase after administration of 100 γ/kg/min for 10

  17. Tuning of the electronic properties of a cyclopentadienylruthenium catalyst to match racemization of electron-rich and electron-deficient alcohols.

    PubMed

    Verho, Oscar; Johnston, Eric V; Karlsson, Erik; Bäckvall, Jan-E

    2011-09-26

    The synthesis of a new series of cyclopentadienylruthenium catalysts with varying electronic properties and their application in racemization of secondary alcohols are described. These racemizations involve two key steps: 1) β-hydride elimination (dehydrogenation) and 2) re-addition of the hydride to the intermediate ketone. The results obtained confirm our previous theory that the electronic properties of the substrate determine which of these two steps is rate determining. For an electron-deficient alcohol the rate-determining step is the β-hydride elimination (dehydrogenation), whereas for an electron-rich alcohol the re-addition of the hydride becomes the rate-determining step. By matching the electronic properties of the catalyst with the electronic properties of the alcohol, we have now shown that a dramatic increase in racemization rate can be obtained. For example, electron-deficient alcohol 15 racemized 30 times faster with electron-deficient catalyst 6 than with the unmodified standard catalyst 4. The application of these protocols will extend the scope of cyclopentadienylruthenium catalysts in racemization and dynamic kinetic resolution. PMID:21882268

  18. D:L-AMINO Acids and the Turnover of Microbial Biomass

    NASA Astrophysics Data System (ADS)

    Lomstein, B. A.; Braun, S.; Mhatre, S. S.; Jørgensen, B. B.

    2015-12-01

    Decades of ocean drilling have demonstrated wide spread microbial life in deep sub-seafloor sediment, and surprisingly high microbial cell numbers. Despite the ubiquity of life in the deep biosphere, the large community sizes and the low energy fluxes in the vast buried ecosystem are still poorly understood. It is not know whether organisms of the deep biosphere are specifically adapted to extremely low energy fluxes or whether most of the observed cells are in a maintenance state. Recently we developed and applied a new culture independent approach - the D:L-amino acid model - to quantify the turnover times of living microbial biomass, microbial necromass and mean metabolic rates. This approach is based on the built-in molecular clock in amino acids that very slowly undergo chemical racemization until they reach an even mixture of L- and D- forms, unless microorganisms spend energy to keep them in the L-form that dominates in living organisms. The approach combines sensitive analyses of amino acids, the unique bacterial endospore marker (dipicolinic acid) with racemization dynamics of stereo-isomeric amino acids. Based on a heating experiment, we recently reported kinetic parameters for racemization of aspartic acid, glutamic acid, serine and alanine in bulk sediment from Aarhus Bay, Denmark. The obtained racemization rate constants were faster than the racemization rate constants of free amino acids, which we have previously applied in Holocene sediment from Aarhus Bay and in up to 10 mio yr old sediment from ODP Leg 201. Another important input parameter for the D:L-amino acid model is the cellular carbon content. It has recently been suggested that the cellular carbon content most likely is lower than previously thought. In recognition of these new findings, previously published data based on the D:L-amino acid model were recalculated and will be presented together with new data from an Arctic Holocene setting with constant sub-zero temperatures.

  19. Chiral separation of amino acids in ultrafiltration through DNA-immobilized cellulose membranes

    NASA Astrophysics Data System (ADS)

    Higuchi, Akon; Hayashi, Akiyuki; Kanda, Naoki; Sanui, Kohei; Kitamura, Hanako

    2005-04-01

    Ultrafiltration experiments for the chiral separation of racemic tryptophan, phenylglycine and phenylalanine were investigated through immobilized DNA membranes having various pore sizes. L-tryptophan preferentially permeated through immobilized DNA membranes with a pore size<2.0 nm (molecular weight cut-off (MWCO)<5000) while D-tryptophan preferentially permeated through immobilized DNA membranes with a pore size>2.0 nm (MWCO>5000). These results are completely opposite tendency in the ultrafiltration of racemic phenylalanine through the immobilized DNA membranes. This may be originated from the different interaction between DNA and tryptophan compared to that between DNA and phenylalanine. However, in both cases the pore size of the immobilized DNA membranes regulated preferential permeation of the enantiomer through the membranes. The immobilized DNA membranes are categorized as channel type membranes and not as affinity membranes. Chiral separation models were proposed from using the chiral separation results of racemic amino acids, preferential adsorption of amino acid enantiomers and EPMA results.

  20. MicroRNA-16 is putatively involved in the NF-κB pathway regulation in ulcerative colitis through adenosine A2a receptor (A2aAR) mRNA targeting

    PubMed Central

    Tian, Ting; Zhou, Yu; Feng, Xiao; Ye, Shicai; Wang, Hao; Wu, Weiyun; Tan, Wenkai; Yu, Caiyuan; Hu, Juxiang; Zheng, Rong; Chen, Zonghao; Pei, Xinyu; Luo, Hesheng

    2016-01-01

    MicroRNAs (miRNAs) act as important post-transcriptional regulators of gene expression by targeting the 3′-untranslated region of their target genes. Altered expression of miR-16 is reported in human ulcerative colitis (UC), but its role in the development of the disease remains unclear. Adenosine through adenosine A2a receptor (A2aAR) could inhibit nuclear factor-kappaB (NF-κB) signaling pathway in inflammation. Here we identified overexpression of miR-16 and down-regulation of A2aAR in the colonic mucosa of active UC patients. We demonstrated that miR-16 negatively regulated the expression of the A2aAR at the post-transcriptional level. Furthermore, transfection of miR-16 mimics promoted nuclear translocation of NF-κB p65 protein and expression of pro-inflammatory cytokines, IFN-γ and IL-8 in colonic epithelial cells. Treatment with miR-16 inhibitor could reverse these effects in cells. The A2aAR-mediated effects of miR-16 on the activation of the NF-κB signaling pathway were confirmed by the A2aAR knockdown assay. Our results suggest that miR-16 regulated the immune and inflammatory responses, at least in part, by suppressing the expression of the A2aAR to control the activation of the NF-κB signaling pathway. PMID:27476546

  1. Comparison of chiral separations of aminophosphonic acids and their aminocarboxylic acid analogs using a crown ether column.

    PubMed

    Barnhart, Wesley W; Xia, Xiaoyang; Jensen, Randy; Gahm, Kyung H

    2013-07-01

    Crown ethers are capable of complexing with primary amines and have been utilized in chromatography to separate amino acid racemates. This application has been extended to resolve (1-amino-1-phenylmethyl)phosphonic acid and (1-aminoethyl)phosphonic acid racemates, along with their aminocarboxylic acid analogs (2-phenylglycine and alanine, respectively), via a ChiroSil RCA crown ether based chiral stationary phase. Effects of the organic modifier, temperature, and acid type and concentration on retention and selectivity were also investigated. Trends in retention and selectivity varied between aminophosponic acids and their aminocarboxylic analogs. Computer modeling and (1)H NMR analyses were performed to potentially gain a better understanding of interactions of the aforementioned molecules with the ChiroSil RCA chiral stationary phase. Theoretical predictions of the most stable conformations for (R)- and (S)-enantiomers were compared to elution order; it was found that the elution order agreed with molecular modeling such that the longest retention correlated with the predicted most stable complex between the enantiomer and crown ether. (1)H NMR demonstrated interactions of aminophosphonic and aminocarboxylic racemates with (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid in solution and was utilized to determine enantiomeric excess of (1-amino-1-phenylmethyl)phosphonic acid after its enantioenrichment via crystallization through diastereomeric salt formation with the crown ether followed by filtration. PMID:23703726

  2. Understanding and identifying amino acid repeats.

    PubMed

    Luo, Hong; Nijveen, Harm

    2014-07-01

    Amino acid repeats (AARs) are abundant in protein sequences. They have particular roles in protein function and evolution. Simple repeat patterns generated by DNA slippage tend to introduce length variations and point mutations in repeat regions. Loss of normal and gain of abnormal function owing to their variable length are potential risks leading to diseases. Repeats with complex patterns mostly refer to the functional domain repeats, such as the well-known leucine-rich repeat and WD repeat, which are frequently involved in protein–protein interaction. They are mainly derived from internal gene duplication events and stabilized by ‘gate-keeper’ residues, which play crucial roles in preventing inter-domain aggregation. AARs are widely distributed in different proteomes across a variety of taxonomic ranges, and especially abundant in eukaryotic proteins. However, their specific evolutionary and functional scenarios are still poorly understood. Identifying AARs in protein sequences is the first step for the further investigation of their biological function and evolutionary mechanism. In principle, this is an NP-hard problem, as most of the repeat fragments are shaped by a series of sophisticated evolutionary events and become latent periodical patterns. It is not possible to define a uniform criterion for detecting and verifying various repeat patterns. Instead, different algorithms based on different strategies have been developed to cope with different repeat patterns. In this review, we attempt to describe the amino acid repeat-detection algorithms currently available and compare their strategies based on an in-depth analysis of the biological significance of protein repeats. PMID:23418055

  3. Quantitative assessment of alkali-reactive aggregate mineral content through XRD using polished sections as a supplementary tool to RILEM AAR-1 (petrographic method)

    SciTech Connect

    Castro, Nelia; Sorensen, Bjorn E.; Broekmans, Maarten A.T.M.

    2012-11-15

    The mineral content of 5 aggregate samples from 4 different countries, including reactive and non-reactive aggregate types, was assessed quantitatively by X-ray diffraction (XRD) using polished sections. Additionally, electron probe microanalyzer (EPMA) mapping and cathodoluminescence (CL) were used to characterize the opal-CT identified in one of the aggregate samples. Critical review of results from polished sections against traditionally powdered specimen has demonstrated that for fine-grained rocks without preferred orientation the assessment of mineral content by XRD using polished sections may represent an advantage over traditional powder specimens. Comparison of data on mineral content and silica speciation with expansion data from PARTNER project confirmed that the presence of opal-CT plays an important role in the reactivity of one of the studied aggregates. Used as a complementary tool to RILEM AAR-1, the methodology suggested in this paper has the potential to improve the strength of the petrographic method.

  4. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, and King Scores for Diagnosis of Esophageal Varices in Liver Cirrhosis: A Retrospective Study.

    PubMed

    Deng, Han; Qi, Xingshun; Peng, Ying; Li, Jing; Li, Hongyu; Zhang, Yongguo; Liu, Xu; Sun, Xiaolin; Guo, Xiaozhong

    2015-01-01

    BACKGROUND Aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, fibrosis index (FI), and King scores might be alternatives to the use of upper gastrointestinal endoscopy for the diagnosis of esophageal varices (EVs) in liver cirrhosis. This study aimed to evaluate their diagnostic accuracy in predicting the presence and severity of EVs in liver cirrhosis. MATERIAL AND METHODS All patients who were consecutively admitted to our hospital and underwent upper gastrointestinal endoscopy between January 2012 and June 2014 were eligible for this retrospective study. Areas under curve (AUCs) were calculated. Subgroup analyses were performed according to the history of upper gastrointestinal bleeding (UGIB) and splenectomy. RESULTS A total of 650 patients with liver cirrhosis were included, and 81.4% of them had moderate-severe EVs. In the overall analysis, the AUCs of these non-invasive scores for predicting moderate-severe EVs and presence of any EVs were 0.506-0.6 and 0.539-0.612, respectively. In the subgroup analysis of patients without UGIB, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.601-0.664 and 0.596-0.662, respectively. In the subgroup analysis of patients without UGIB or splenectomy, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.627-0.69 and 0.607-0.692, respectively. CONCLUSIONS APRI, AAR, FIB-4, FI, and King scores had modest diagnostic accuracy of EVs in liver cirrhosis. They might not be able to replace the utility of upper gastrointestinal endoscopy for the diagnosis of EVs in liver cirrhosis. PMID:26687574

  5. Syntheses, structures and photocatalytic properties of five new praseodymium-antimony oxochlorides: from discrete clusters to 3D inorganic-organic hybrid racemic compounds.

    PubMed

    Zou, Guo-Dong; Wang, Ze-Ping; Song, Ying; Hu, Bing; Huang, Xiao-Ying

    2014-07-14

    Five novel praseodymium-antimony oxochloride (Pr-Sb-O-Cl) cluster-based compounds, namely (2-MepyH)2[Fe(1,10-phen)3]2[Pr4Sb12O18Cl14.6(OH)2.4(Hsal)]·H2O (1), (2-MepyH)2[Fe(1,10-phen)3]4{[Pr4Sb12O18Cl13.5(OH)0.5](bcpb)2[Pr4Sb12O18Cl13.5(OH)0.5]}·42H2O (2), (3-MepyH)2[Fe(1,10-phen)3]{[Pr4Sb12O18Cl13(H2O)2](bcpb)}·2(3-Mepy)·3H2O (3), [Fe(1,10-phen)3]2{[Pr4Sb12O18Cl10(H2O)2](bcpb)2}·3(3-Mepy)·13H2O (4), and (2-MepyH)6[Fe(1,10-phen)3]10{[Pr4Sb12O18Cl13(OH)2]2[Pr4Sb12O18Cl9][Pr4Sb12O18Cl9(OH)2]2(Hpdc)10(pdc)2}·110H2O (5) (2-Mepy = 2-methylpyridine, 3-Mepy = 3-methylpyridine, 1,10-phen = 1,10-phenanthroline, H2sal = salicylic acid, H3bcpb = 3,5-bis(4-carboxyphenoxy)benzoic acid, H3pdc = 3,5-pyrazoledicarboxylic acid) have been solvothermally synthesized and structurally characterized. Compound 1 is the first zero-dimensional (0D) Pr-Sb-O-Cl cluster decorated by an organic ligand. Compounds 2-4 are constructed from the same H3bcpb ligands but adopt different structures: 2 represents a rare example of a one-dimensional (1D) nanotubular structure based on high-nuclearity clusters; 3 exhibits a two-dimensional (2D) mono-layered structure, in which left-handed and right-handed helical chains are alternately arranged, while 4 features a double-layered structure with an unprecedented (3,3,6)-connected 3-nodal topological net. Compound 5 is a unique three-dimensional (3D) 2-fold interpenetrating racemic compound, simultaneously containing three kinds of Pr-Sb-O-Cl-pdc clusters. UV-light photocatalytic H2 evolution activity was observed for compound 3 with Pt as a co-catalyst and MeOH as a sacrificial electron donor. In addition, the magnetic properties of compounds 1 and 5 are also studied. PMID:24869770

  6. Synthesis of racemic and chiral BEDT-TTF derivatives possessing hydroxy groups and their achiral and chiral charge transfer complexes

    PubMed Central

    Krivickas, Sara Jane; Hashimoto, Chiho; Yoshida, Junya; Ueda, Akira; Takahashi, Kazuyuki; Wallis, John D

    2015-01-01

    Summary Chiral molecular crystals built up by chiral molecules without inversion centers have attracted much interest owing to their versatile functionalities related to optical, magnetic, and electrical properties. However, there is a difficulty in chiral crystal growth due to the lack of symmetry. Therefore, we made the molecular design to introduce intermolecular hydrogen bonds in chiral crystals. Racemic and enantiopure bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) derivatives possessing hydroxymethyl groups as the source of hydrogen bonds were designed. The novel racemic trans-vic-(hydroxymethyl)(methyl)-BEDT-TTF 1, and racemic and enantiopure trans-vic-bis(hydroxymethyl)-BEDT-TTF 2 were synthesized. Moreover, the preparations, crystal structure analyses, and electrical resistivity measurements of the novel achiral charge transfer salt θ21-[(S,S)-2]3[(R,R)-2]3(ClO4)2 and the chiral salt α’-[(R,R)-2]ClO4(H2O) were carried out. In the former θ21-[(S,S)-2]3[(R,R)-2]3(ClO4)2, there are two sets of three crystallographically independent donor molecules [(S,S)-2]2[(R,R)-2] in a unit cell, where the two sets are related by an inversion center. The latter α’-[(R,R)-2]ClO4(H2O) is the chiral salt with included solvent H2O, which is not isostructural with the reported chiral salt α’-[(S,S)-2]ClO4 without H2O, but has a similar donor arrangement. According to the molecular design by introduction of hydroxy groups and a ClO4 − anion, many intermediate-strength intermolecular hydrogen bonds (2.6–3.0 Å) were observed in these crystals between electron donor molecules, anions, and included H2O solvent, which improve the crystallinity and facilitate the extraction of physical properties. Both salts are semiconductors with relatively low resistivities at room temperature and activation energies of 1.2 ohm cm with E a = 86 meV for θ21-[(S,S)-2]3[(R,R)-2]3(ClO4)2 and 0.6 ohm cm with E a = 140 meV for α'-[(R,R)-2]2ClO4(H2O), respectively. The variety of donor

  7. Alpine re-activation of pre-Alpine structures: details from a large-scale shear zone in the Aar massif (Central Alps)

    NASA Astrophysics Data System (ADS)

    Wehrens, Philip; Baumberger, Roland; Herwegh, Marco

    2013-04-01

    The Aar massif belongs to the external massifs of the Alps and is mainly composed of granitoids and gneisses. Post-Variscan granitoid rocks have intruded old gneisses belonging to the pre-Variscan basement. Despite numerous detailed studies in the past decades, the overall exhumation history and the associated massif internal deformation (internal strain distribution and its evolution in time, kinematics etc.) are largely unknown at present. In this project, we aim to investigate the role of shear zones in the deformation history at a variety of scales. In this context it is important to understand their microstructural evolution, the involved deformation processes, kinematics and relative ages as well as the associated changes in rheology. A detailed study was conducted along a major shear zone located at the southern margin of the Aar massif (running from Furka to Grimsel Pass and Oberaar Glacier), where the Grimsel Granodiorite (GrGr) is juxtapositioned to strongly foliated gneisses. Preliminary results show that a crenulation of these gneisses predates the age of the granitoid intrusion, meaning they must be older than 298 Ma. The crenulation and a related axial plane foliation (145/80°) define mechanical anisotropies within these Pre-Variscan rocks. The intruding granite has exploited these anisotropies a first time during its emplacement in post-Variscan times. The lithological boundary between the intruded GrGr and Pre-Variscan rocks causes strain again to localize during Alpine deformation and results in a 40 m wide large-scale shear zone. The older part of the shear zone shows cm-scale shear zones with vertical lineations shearing off the aforementioned pre-Alpine axial plane foliation. Hence the contact is reactivated, now as Alpine normal/ reverse fault, a second time. Towards the youngest parts of the shear zone the stretching lineation on the shear surfaces turns from vertical towards a subhorizontal position, indicating a change from initial vertical

  8. Helical sense selective domains and enantiomeric superhelices generated by Langmuir-Schaefer deposition of an axially racemic chiral helical polymer

    NASA Astrophysics Data System (ADS)

    Rodríguez, R.; Ignés-Mullol, J.; Sagués, F.; Quiñoá, E.; Riguera, R.; Freire, F.

    2016-02-01

    The chiral polymer poly-(R)-1 behaves in solution, despite its chiral pendants, as a dynamic axially racemic (i.e., 1 : 1) mixture of left- and right-handed helices, but its deposition on graphite by a Langmuir-Schaefer (LS) technique leads to a helical sense-selective packing that forms separate enantiomeric domains of left- and right-handed helical chains observed by high resolution atomic force microscopy (AFM). The polymer structure within these domains is very uniform, seldom altered by the presence of reversals, grouped always in contiguous pairs maintaining a single helical sense along the polymer chain. The LS deposition technique has been shown to be crucial to obtain good quality monolayers from poly-(R)-1 and other poly(phenylacetylene)s (PPAs: poly-2, poly-3 and poly-4) with short pendants, where spin coating, drop casting and Langmuir-Blodgett (LB) failed, and suggests that this technique could be the method of choice for the preparation of 2D monolayers for high resolution AFM studies of PPAs with short pendants. Key helical parameters (i.e., sense, pitch, packing angle) are easily measured in this way.The chiral polymer poly-(R)-1 behaves in solution, despite its chiral pendants, as a dynamic axially racemic (i.e., 1 : 1) mixture of left- and right-handed helices, but its deposition on graphite by a Langmuir-Schaefer (LS) technique leads to a helical sense-selective packing that forms separate enantiomeric domains of left- and right-handed helical chains observed by high resolution atomic force microscopy (AFM). The polymer structure within these domains is very uniform, seldom altered by the presence of reversals, grouped always in contiguous pairs maintaining a single helical sense along the polymer chain. The LS deposition technique has been shown to be crucial to obtain good quality monolayers from poly-(R)-1 and other poly(phenylacetylene)s (PPAs: poly-2, poly-3 and poly-4) with short pendants, where spin coating, drop casting and Langmuir

  9. On the reported optical activity of amino acids in the Murchison meteorite

    USGS Publications Warehouse

    Bada, J.L.; Cronin, J.R.; Ho, M.-S.; Kvenvolden, K.A.; Lawless, J.G.; Miller, S.L.; Oro, J.; Steinberg, S.

    1983-01-01

    In analyses of extracts from the Murchison meteorite (a carbonaceous chondrite), Engel and Nagy1 reported an excess of L-enantiomers for several protein amino acids but found that the non-protein amino acids were racemic. They suggested that the excess of L-isomers might have resulted from an asymmetric synthesis or decomposition. Their results disagree with those obtained previously2-4 and they claim this is due to improved methodology. In fact, their extraction method and analytical procedure (gas chromatography-mass spectrometry, GC-MS) was similar to those used in the original report2 of amino acids in the Murchison meteorite except that they used specific ion monitoring in the GC-MS measurements. We found the results of Engel and Nagy odd in that likely contaminants (the protein amino acids ala, leu, glu, asp and pro) were nonracemic while unlikely contaminants (isovaline and ??-amino-n-butyric acid) were racemic. For example, Engel and Nagy report that the leucine is ???90% L-enantiomer in the water-extracted sample whereas isovaline (??-methyl-??-aminobutyric acid) is racemic. It would be most unusual for an abiotic stereoselective decomposition or synthesis of amino acids to occur with protein amino acids but not with non-protein amino acids. We now show here that the explanation of terrestrial contamination is consistent with their results and is much more probable. ?? 1983 Nature Publishing Group.

  10. Amino acids in the Yamato carbonaceous chrondrite from Antarctica

    NASA Technical Reports Server (NTRS)

    Shimoyama, A.; Ponnamperuma, C.; Yanai, K.

    1979-01-01

    Evidence for the presence of amino acids of extraterrestrial origin in the Antarctic Yamato carbonaceous chrondrite is presented. Hydrolyzed and nonhydrolyzed water-extracted amino acid samples from exterior, middle and interior portions of the meteorite were analyzed by an amino acid analyzer and by gas chromatography of N-TFA-isopropyl amino acid derivatives. Nine protein and six nonprotein amino acids were detected in the meteorite at abundances between 34 and less than one nmole/g, with equal amounts in interior and exterior portions. Nearly equal abundances of the D and L enantiomers of alanine, aspartic acid and glutamic acid were found, indicating the abiotic, therefore extraterrestrial, origin of the amino acids. The Antarctic environment and the uniformity of protein amino acid abundances are discussed as evidence against the racemization of terrestrially acquired amino acids, and similarities between Yamato amino acid compositions and the amino acid compositions of the Murchison and Murray type II carbonaceous chrondrites are indicated.

  11. Growth of exfoliation joints and near-surface stress orientations inferred from fractographic markings observed in the upper Aar valley (Swiss Alps)

    NASA Astrophysics Data System (ADS)

    Ziegler, Martin; Loew, Simon; Bahat, Dov

    2014-06-01

    Granitic rock mass of the upper Aar valley (Grimsel area, Switzerland) contains distinct generations of exfoliation joints, which formed during different stages of the Pleistocene, subparallel to distinct glacial valley palaeotopography. The bulk of exfoliation joints shows prominent, common fractographic features: (1) radial plumose structures with distinct plume axes; (2) arrest marks superimposed by plumose striations; and (3) gradually-developing en échelon fringe cracks. Multiple arrest marks reveal that exfoliation joints formed incrementally and, together with the absence of hackle fringes, suggest stable, i.e., subcritical fracturing conditions. Smooth transitions from plumose structures on the parent plane to en échelon fringe cracks, combined with non-systematic stepping senses of fringe cracks, suggest local (vs. temporal) stress field variations. Assuming that plume axes formed parallel to the maximum principal compressive stress (σ1) enables us to infer near-surface palaeostress orientations and compare them with classical borehole-based in-situ stress data. The majority of plume axes suggest (1) persistently subhorizontal to slightly inclined σ1 orientations at trough valley slopes and (2) near-surface variability of σ1 orientations originating from topographic perturbation caused by glacial valley erosion superimposed on the regional stress field. Our investigations of fracture surface morphologies yield unique insights into exfoliation fracture formation, such as directional trends of fracture propagation and associated palaeostress orientations within Alpine valley slopes.

  12. (+)-Gibberellin C: hydrogen-bonding pattern of the monohydrate of a non-racemic pentacyclic diterpenoid.

    PubMed

    Thompson, H W; Brunskill, A P; Lalancette, R A

    2000-12-01

    In the monohydrate of the title compound, (+)-2beta, 4aalpha-dihydroxy-1,7-dimethyl-8-oxo-4bbeta,7alpha- gibbane-1alpha, 10beta-dicarboxylic acid-1,4a-lactone, C(19)H(24)O(6).H(2)O, intermolecular hydrogen bonding progresses helically along b from carboxyl to ketone [O...O = 2.694 (5) A]. The carboxyl and lactone carbonyl groups in translationally related molecules within a helix both accept hydrogen bonds from the same water of hydration. The oxygen of this water in turn accepts a hydrogen bond from the hydroxyl group of a third screw-related molecule in an adjacent counterdirectionally oriented helix, yielding a complex three-dimensional hydrogen-bonding array. Intermolecular O...H-C close contacts were found to the carboxyl and lactone carbonyls, the hydroxyl, and the water. PMID:11119009

  13. Helical sense selective domains and enantiomeric superhelices generated by Langmuir-Schaefer deposition of an axially racemic chiral helical polymer.

    PubMed

    Rodríguez, R; Ignés-Mullol, J; Sagués, F; Quiñoá, E; Riguera, R; Freire, F

    2016-02-14

    The chiral polymer poly-(R)-1 behaves in solution, despite its chiral pendants, as a dynamic axially racemic (i.e., 1 : 1) mixture of left- and right-handed helices, but its deposition on graphite by a Langmuir-Schaefer (LS) technique leads to a helical sense-selective packing that forms separate enantiomeric domains of left- and right-handed helical chains observed by high resolution atomic force microscopy (AFM). The polymer structure within these domains is very uniform, seldom altered by the presence of reversals, grouped always in contiguous pairs maintaining a single helical sense along the polymer chain. The LS deposition technique has been shown to be crucial to obtain good quality monolayers from poly-(R)-1 and other poly(phenylacetylene)s (PPAs: poly-2, poly-3 and poly-4) with short pendants, where spin coating, drop casting and Langmuir-Blodgett (LB) failed, and suggests that this technique could be the method of choice for the preparation of 2D monolayers for high resolution AFM studies of PPAs with short pendants. Key helical parameters (i.e., sense, pitch, packing angle) are easily measured in this way. PMID:26791332

  14. The pharmacokinetics of pimobendan enantiomers after oral and intravenous administration of racemate pimobendan formulations in healthy dogs.

    PubMed

    Bell, E T; Devi, J L; Chiu, S; Zahra, P; Whittem, T

    2016-02-01

    Pimobendan is a benzimidazole-pyridazinone derivative, marketed as a racemic mixture for the management of canine heart failure. Pharmacokinetics of the enantiomers of pimobendan and its oral bioavailability have not been described in dogs. The aim of this study was to describe pharmacokinetics of three formulations of pimobendan in healthy dogs: the licensed capsule product, and novel liquid and intravenous formulations. A three-period, nested randomized two-treatment crossover design was used. Pimobendan was administered p.o. at 0.25 and i.v. at 0.125 mg/kg. Blood and plasma samples were analysed by liquid chromatography-mass spectrometry. Noncompartmental modelling was used to describe the pharmacokinetics. Parameters were compared between formulations using a general linear model. Bioequivalence of the oral formulations was tested using CI90 for AUC(0-∞) and Cmax . Bioavailability of pimobendan after oral dosing was 70%. Liquid and capsule formulations were bioequivalent only for AUC. The positive enantiomer of pimobendan (PE) had a larger volume of distribution than the negative enantiomer (NE) (281 ± 48 vs. 215 ± 68 mL/kg; P = 0.003) and a shorter half-life (21.7 vs. 29.9 min; P = 0.004). The NE was distributed more quickly than the PE into blood cells. Enantiomers of pimobendan have differing absorption, distribution and elimination. The pharmacokinetics of pimobendan in healthy dogs was described. PMID:25989021

  15. Mass-transfer limitations for immobilized enzyme-catalyzed kinetic resolution of racemate in a fixed-bed reactor.

    PubMed

    Xiu, G H; Jiang, L; Li, P

    2001-07-01

    A mathematical model has been developed for immobilized enzyme-catalyzed kinetic resolution of racemate in a fixed-bed reactor in which the enzyme-catalyzed reaction (the irreversible uni-uni competitive Michaelis-Menten kinetics is chosen as an example) was coupled with intraparticle diffusion, external mass transfer, and axial dispersion. The effects of mass-transfer limitations, competitive inhibition of substrates, deactivation on the enzyme effective enantioselectivity, and the optical purity and yield of the desired product are examined quantitatively over a wide range of parameters using the orthogonal collocation method. For a first-order reaction, an analytical solution is derived from the mathematical model for slab-, cylindrical-, and spherical-enzyme supports. Based on the analytical solution for the steady-state resolution process, a new concise formulation is presented to predict quantitatively the mass-transfer limitations on enzyme effective enantioselectivity and optical purity and yield of the desired product for a continuous steady-state kinetic resolution process in a fixed-bed reactor. PMID:11353408

  16. Comparison of levalbuterol and racemic albuterol combined with ipratropium bromide in acute pediatric asthma: a randomized controlled trial.

    PubMed

    Ralston, Mark E; Euwema, Michael S; Knecht, Kenneth R; Ziolkowski, Timothy J; Coakley, Timothy A; Cline, Shane M

    2005-07-01

    Our study compared levalbuterol (LEV) to the combination of racemic albuterol (RAC) and ipratropium bromide (IB) in 140 patients aged 6-18 years presenting to a tertiary hospital Emergency Department with acute asthma and a peak expired flow rate (PEF)<80% predicted. Patients were randomized to: LEV (

  17. Microfluidic chip capillary electrophoresis coupled with electrochemiluminescence for enantioseparation of racemic drugs using central composite design optimization.

    PubMed

    Guo, Wen Peng; Rong, Zhi Bin; Li, Ying Hong; Fung, Ying Sing; Gao, Guo Quan; Cai, Zhi Ming

    2013-11-01

    Optimization based on central composite design (CCD) for enantioseparation of anisodamine (AN), atenolol (AT), and metoprolol (ME) in human urine was developed using a microfluidic chip-CE device. Coupling the flexible and wide working range of microfluidic chip-CE device to CCD for chiral separation of AN, AT, and ME in human urine, a total of 15 experiments is needed for the optimization procedure as compared to 75 experiments using the normal one variable at a time optimization. The optimum conditions obtained are found to be more robust as shown by the curvature effects of the interaction factors. The developed microfluidic chip-CE-ECL system with adjustable dilution ratios has been validated by satisfactory recoveries (89.5-99% for six enanotiomers) in urine sample analysis. The working range (0.3-600 μM), repeatability (3.1-4.9% RSD for peak height and 4.0-5.2% RSD for peak area), and detection limit (0.3-0.6 μM) of the method developed are found to meet the requirements for bedside monitoring of AN, AT, and ME in patients under critical conditions. In summary, the hyphenation of CCD with the microfluidic chip-CE device is shown to offer a rapid means for optimizing the working conditions on simultaneous separation of three racemic drugs using the microfluidic chip-CE device developed. PMID:24037989

  18. A comparative Analysis of In Vitro and In Vivo Efficacies of the Enantiomers of Thioridazine and Its Racemate

    PubMed Central

    Christensen, Jørn B.; Hendricks, Oliver; Chaki, Shaswati; Mukherjee, Sayanti; Das, Ayan; Pal, Tapan K.; Dastidar, Sujata G.; Kristiansen, Jette E.

    2013-01-01

    A long list of chemotherapeutical drugs used in the treatment of the peripheral and the central nervous systems possess anti-microbial activity. Some of these neurotropic compounds are chiral, with the one stereo isomeric form exaggerating reduced neurotropism. This is the case for the levorotatory form of thioridazine. The phenothiazine thioridazine is an interesting compound, characterized by exhibiting a significant growth inhibiting activity on a wide array of micro-organisms. Thioridazine is characterized by another challenging feature, because the compound is concentrated in certain human tissue cells. The present study describes a comparative study of the two enantiomers as well as the racemic form of thioridazine. The study exploits the stereochemical aspect and the in vitro and in vivo potential of these compounds, with a focus on the effects on Gram negative organism Salmonella enterica serover Typhimurium. In summary, the results of this study yielded a significant antibacterial activity of all forms of thioridazine, indicating the levorotatory (–)- form to be superior in terms of both its in vitro and in vivo efficacies. PMID:23505431

  19. Anaesthesia recovery quality after racemic ketamine or S-ketamine administration to male cats undergoing neutering surgery.

    PubMed

    Larenza, M P; Althaus, H; Conrot, A; Balmer, C; Schatzmann, U; Bettschart-Wolfensberger, R

    2008-12-01

    Postoperative anaesthesia recovery and analgesia qualities were compared in cats anaesthetised with racemic ketamine (RS-ket) or S-ketamine (S-ket) undergoing orchiectomy. Twenty client-owned male cats received medetomidine (0.03 mg/kg) and S-ket (6 mg/kg; n = 10) or RS-ket (10 mg/kg; n = 10), all intramuscularly. After routine orchiectomy, animals received atipamezole (0.15 mg/kg) intramuscularly. Thirty and 60 min after atipamezole administration, one observer unaware of the treatment identity evaluated analgesia using a visual analogue scale (VAS) and, by means of four points scales, sedation, unprovoked behaviour and behavioural reactions to external stimuli. Cats with a VAS > or = 15 mm were to receive butorphanol. Times to sternal and standing positions were recorded. After 60 min, cats were given carprofen (4 mg/kg) subcutaneously. Anaesthesia with S-ket, at 60% of the RS-ket dose, provided faster recoveries. At 60 min, undisturbed cats in S-ket group had a trend towards fewer behavioural changes. Cats in RS-ket group were more sedate at 30 min and responded with a lower intensity to external stimulation. Immediate postoperative analgesia was considered adequate for both groups and no cat required butorphanol administration. PMID:19034844

  20. The Origin of Amino Acids in Lunar Regolith Samples

    NASA Technical Reports Server (NTRS)

    Cook, Jamie E.; Callahan, Michael P.; Dworkin, Jason P.; Glavin, Daniel P.; McLain, Hannah L.; Noble, Sarah K.; Gibson, Everett K., Jr.

    2016-01-01

    We analyzed the amino acid content of seven lunar regolith samples returned by the Apollo 16 and Apollo 17 missions and stored under NASA curation since collection using ultrahigh-performance liquid chromatography with fluorescence detection and time-of-flight mass spectrometry. Consistent with results from initial analyses shortly after collection in the 1970s, we observed amino acids at low concentrations in all of the curated samples, ranging from 0.2 parts-per-billion (ppb) to 42.7 ppb in hot-water extracts and 14.5 ppb to 651.1 ppb in 6M HCl acid-vapor-hydrolyzed, hot-water extracts. Amino acids identified in the Apollo soil extracts include glycine, D- and L-alanine, D- and L-aspartic acid, D- and L-glutamic acid, D- and L-serine, L-threonine, and L-valine, all of which had previously been detected in lunar samples, as well as several compounds not previously identified in lunar regoliths: -aminoisobutyric acid (AIB), D-and L-amino-n-butyric acid (-ABA), DL-amino-n-butyric acid, -amino-n-butyric acid, -alanine, and -amino-n-caproic acid. We observed an excess of the L enantiomer in most of the detected proteinogenic amino acids, but racemic alanine and racemic -ABA were present in some samples.

  1. Bulky metallocavitands with a chiral cavity constructed by aluminum and magnesium atrane-likes: enantioselective recognition and separation of racemic alcohols.

    PubMed

    Li, Yingguo; Yu, Dawei; Dai, Zhongran; Zhang, Jinjin; Shao, Yongliang; Tang, Ning; Wu, Jincai

    2015-03-28

    Seven new type metallocavitand complexes 1–7 were synthesized via the self-assembly of aluminum and magnesium atrane-likes. The recognition of R-2-butanol from racemic 2-butanol can be achieved in the chiral cavity of metallocavitand complex 5. The crystal structure of complex 5 showed that the enantioselectivity of the center cavity for the inclusion of two 2-butanol molecules is higher than that of the groups at the outer rim, which indicates that the size-limited cavity is more sensitive to the chirality of 2-butanol. Furthermore, desorption of R-2-butanol is successful through vacuumization which afforded complex 6 and gives R-2-butanol with an enantiomeric excess (ee) value of 53(±1)%. The reaction of enantiopure H3L2, MgnBu2, and racemic 1-phenylethanol afforded complex 7. The structure of complex 7 showed that the center cavity was occupied by three H2O molecules and one molecular R-1-phenylethanol suspended in the outer rim of the metallocavitand via a hydrogen bond, which indicated that 1-phenylethanol is too bulky for the size-limited cavity. Because a certain amount of racemic 1-phenylethanol is also co-crystallized in the unit cell, the final separated 1-phenylethanol has an ee value of 33(±1)%. The host–guest mechanism for the separation is clearly determined through X-ray crystal structural analysis. PMID:25710446

  2. Engineering Porous Organic Cage Crystals with Increased Acid Gas Resistance.

    PubMed

    Zhu, Guanghui; Hoffman, Christopher D; Liu, Yang; Bhattacharyya, Souryadeep; Tumuluri, Uma; Jue, Melinda L; Wu, Zili; Sholl, David S; Nair, Sankar; Jones, Christopher W; Lively, Ryan P

    2016-07-25

    Both known and new CC3-based porous organic cages are prepared and exposed to acidic SO2 in vapor and liquid conditions. Distinct differences in the stability of the CC3 cages exist depending on the chirality of the diamine linkers used. The acid catalyzed CC3 degradation mechanism is probed via in situ IR and a degradation pathway is proposed and supported with computational results. CC3 crystals synthesized with racemic mixtures of diaminocyclohexane exhibited enhanced stability compared to CC3-R and CC3-S. Confocal fluorescent microscope images reveal that the stability difference in CC3 species originates from an abundance of mesoporous grain boundaries in CC3-R and CC3-S, allowing facile access of aqueous SO2 throughout the crystal, promoting decomposition. These grain boundaries are absent from CC3 crystals made with racemic linkers. PMID:27253350

  3. Enantioseparation of Mandelic Acid Enantiomers With Magnetic Nano-Sorbent Modified by a Chiral Selector.

    PubMed

    Tarhan, Tuba; Tural, Bilsen; Tural, Servet; Topal, Giray

    2015-11-01

    In this study, R(+)-α-methylbenzylamine-modified magnetic chiral sorbent was synthesized and assessed as a new enantioselective solid phase sorbent for separation of mandelic acid enantiomers from aqueous solutions. The chemical structures and magnetic properties of the new sorbent were characterized by vibrating sample magnetometry, transmission electron microscopy, Fourier transform infrared spectroscopy, and dynamic light scattering. The effects of different variables such as the initial concentration of racemic mandelic acid, dosage of sorbent, and contact time upon sorption characteristics of mandelic acid enantiomers on magnetic chiral sorbent were investigated. The sorption of mandelic acid enantiomers followed a pseudo-second-order reaction and equilibrium experiments were well fitted to a Langmuir isotherm model. The maximum adsorption capacity of racemic mandelic acid on to the magnetic chiral sorbent was found to be 405 mg g(-1). The magnetic chiral sorbent has a greater affinity for (S)-(+)-mandelic acid compared to (R)-(-)-mandelic acid. The optimum resolution was achieved with 10 mL 30 mM of racemic mandelic acid and 110 mg of magnetic chiral sorbent. The best percent enantiomeric excess values (up to 64%) were obtained by use of a chiralpak AD-H column. PMID:26370608

  4. (±)-2-Oxocyclo­penta­neacetic acid: catemeric hydrogen bonding in a γ-keto acid

    PubMed Central

    Efthimiopoulos, Georgia; Papadakis, Markos M.; Thompson, Hugh W.; Lalancette, Roger A.

    2009-01-01

    The title racemate, C7H10O3, aggregates in the solid as acid-to-ketone hydrogen-bonding catemers [O⋯O = 2.7050 (13) Å and O—H⋯O = 166.1 (17)°] having glide-related components. Four such heterochiral chains, paired centrosymmetrically about (, , ) in the cell, proceed through the cell in the 010 direction, with alignment with respect to the c axis of ++−−. PMID:21582637

  5. Development of a Method for the N-Arylation of Amino Acid Esters with Aryl Triflates.

    PubMed

    King, Sandra M; Buchwald, Stephen L

    2016-08-19

    A general method for the N-arylation of amino acid esters with aryl triflates is described. Both α- and β-amino acid esters, including methyl, tert-butyl, and benzyl esters, are viable substrates. Reaction optimization was carried out by design of experiment (DOE) analysis using JMP software. The mild reaction conditions, which use t-BuBrettPhos Pd G3 or G4 precatalyst, result in minimal racemization of the amino acid ester. This method is the first synthetic application of the t-BuBrettPhos Pd G4 precatalyst. Mechanistic studies show that the observed erosion in enantiomeric excess is due to racemization of the amino acid ester starting material and not of the product. PMID:27498618

  6. Bispalladacycle-catalyzed Brønsted acid/base-promoted asymmetric tandem azlactone formation-Michael addition.

    PubMed

    Weber, Manuel; Jautze, Sascha; Frey, Wolfgang; Peters, René

    2010-09-01

    Cooperative activation by a soft bimetallic catalyst, a hard Brønsted acid, and a hard Brønsted base has allowed the formation of highly enantioenriched, diastereomerically pure masked alpha-amino acids with adjacent quaternary and tertiary stereocenters in a single reaction starting from racemic N-benzoylated amino acids. The products can, for example, be used to prepare bicyclic dipeptides. PMID:20715774

  7. Enantiomeric excesses in meteoritic amino acids

    NASA Technical Reports Server (NTRS)

    Cronin, J. R.; Pizzarello, S.

    1997-01-01

    Gas chromatographic-mass spectral analyses of the four stereoisomers of 2-amino-2,3-dimethylpentanoic acid (dl-alpha-methylisoleucine and dl-alpha-methylalloisoleucine) obtained from the Murchison meteorite show that the L enantiomer occurs in excess (7.0 and 9.1%, respectively) in both of the enantiomeric pairs. Similar results were obtained for two other alpha-methyl amino acids, isovaline and alpha-methylnorvaline, although the alpha hydrogen analogs of these amino acids, alpha-amino-n-butyric acid and norvaline, were found to be racemates. With the exception of alpha-amino-n-butyric acid, these amino acids are either unknown or of limited occurrence in the biosphere. Because carbonaceous chondrites formed 4.5 billion years ago, the results are indicative of an asymmetric influence on organic chemical evolution before the origin of life.

  8. Racemic gamma vinyl-GABA (R,S-GVG) blocks methamphetamine-triggered reinstatement of conditioned place preference

    PubMed Central

    DEMARCO, AMY; DALAL, REEMA M.; PAI, JESSICA; AQUILINA, STEFANIE D.; MULLAPUDI, UMA; HAMMEL, CRYSTIE; KOTHARI, SHIVA K.; KAHANDA, MILAN; LIEBLING, COURTNEY N.B.; PATEL, VINAL; SCHIFFER, WYNNE K.; BRODIE, JONATHAN D.; DEWEY, STEPHEN L.

    2016-01-01

    Preventing relapse poses a significant challenge to the successful management of methamphetamine (METH) dependence. Although no effective medication currently exists for its treatment, racemic gamma vinyl-GABA (R,S-GVG, vigabatrin) shows enormous potential as it blocks both the neurochemical and behavioral effects of a variety of drugs, including METH, heroin, morphine, ethanol, nicotine, and cocaine. Using the reinstatement of a conditioned place preference (CPP) as an animal model of relapse, the present study specifically investigated the ability of an acute dose of R,S-GVG to block METH-triggered reinstatement of a METH-induced CPP. Animals acquired a METH CPP following a 20 day period of conditioning, in which they received 10 pairings of alternating METH and saline injections. During conditioning, rats were assigned to one of four METH dosage groups: 1.0, 2.5, 5.0, or 10.0 mg/kg (i.p., n = 8/group). Animals in all dosage groups demonstrated a robust and consistent CPP. This CPP was subsequently extinguished in each dosage group with repeated saline administration. Upon extinction, all groups reinstated following an acute METH challenge. On the following day, an acute dose of R,S-GVG (300 mg/kg, i.p.) was administered 2.5 hours prior to an identical METH challenge. R,S-GVG blocked METH-triggered reinstatement in all four groups. Given that drug re-exposure may potentiate relapse to drug-seeking behavior, the ability of R,S-GVG to block METH-triggered reinstatement offers further support for its use in the successful management of METH dependence. PMID:19016239

  9. Antinociceptive Effect of Racemic Flurbiprofen and Caffeine Co-Administration in an Arthritic Gout-Type Pain in Rats.

    PubMed

    Liévano-Reyes, Ricardo; Pérez-Méndez, Hermínia Ines; Solís-Oba, Aida; Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; López-Muñoz, Francisco Javier

    2016-06-01

    Preclinical Research Drug combinations are routinely used in the treatment of pain. In drug associations, adjuvants such as caffeine, are employed with different non-steroidal anti-inflammatories drugs (NSAIDs), however, at present does not exist studies showing the effect of the combination of racemic flurbiprofen (rac-Flur) in association with caffeine. The objective of this work was to evaluate the combination of rac-Flur + caffeine oral in arthritic gout-type pain in rats. The antinociceptive effects of the rac-Flur alone and in combination with caffeine were analyzed on a pain-induced functional impairment model in rat. rac-Flur induced a dose-dependent antinociceptive effect and caffeine did not present any effect. The combination of rac-Flur and caffeine achieve a higher percentage of antinociceptive effect compared with the individual administration of rac-Flur. The dose-response curve (DRCs) shows that the combination of rac-Flur (31.6 mg/kg) + caffeine (17.8 mg/kg) exhibited the maximal antinociceptive efficacy (294.0 ± 21.2 area units), while rac-Flur alone (31.6 mg/kg) showed 207.2 ± 35.2 au, thus indicating an increase in efficacy (potentiation). Furthermore, the DRCs of the combinations presented a displacement to the left, indicating a change in the potency. Caffeine is able to increase the effect of rac-Flur in the arthritic gout-type pain in rats. Drug Dev Res 77 : 192-198, 2016.   © 2016 Wiley Periodicals, Inc. PMID:27241234

  10. Stable isotope and Ar/Ar evidence of prolonged multiscale fluid flow during exhumation of orogenic crust: Example from the Mont Blanc and Aar Massifs (NW Alps)

    NASA Astrophysics Data System (ADS)

    Rossi, M.; Rolland, Y.

    2014-09-01

    The spatial and temporal scales and the geometry of fluid pathways in a collisional orogen are investigated using stable isotope analysis (O, C, and H) and 40Ar/39Ar dating of vein minerals formed at circa 11-16 Ma in the Mont Blanc and the Aar External Crystalline Massifs. In both massifs 40Ar/39Ar dating of veins adularia provides evidence for progressive crystallization from 16 to 9 Ma, and mainly at 11-12 Ma following veins opening during shear zone activity. The fluid flow duration thus ranges from 4 to 5 Ma in the two massifs. The δ18O values of vein quartz and calcite are similar to those of undeformed crystalline and sedimentary host rocks, suggesting rock buffering, while carbon isotope ratios of vein calcites fall into three compositional groups. A-type veins have δ13C values that are buffered by the Helvetic metasediments, which suggests that these veins formed in a closed system from a locally derived CO2-rich fluid. The fluid in equilibrium with C-type veins has depleted δ13C values similar to mantle-CO2, while the intermediate δ13C values of B-type veins suggest mixing between the A-type and C-type fluids. These results are in agreement with crustal- to lithosphere-scale upward vertical fluid flow along vertical shear zones related to the strike-slip system bounding the Adriatic block since 16-20 Ma, connecting a deep-seated fluid to some downward flow in the sedimentary cover of External Crystalline Massifs.

  11. Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis.

    PubMed

    Tang, Xiaohu; Keenan, Melissa M; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J Will; Freedland, Stephen J; Murphy, Susan K; Chi, Jen-Tsan

    2015-04-01

    Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine

  12. Comprehensive Profiling of Amino Acid Response Uncovers Unique Methionine-Deprived Response Dependent on Intact Creatine Biosynthesis

    PubMed Central

    Tang, Xiaohu; Keenan, Melissa M.; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J. Will; Freedland, Stephen J.; Murphy, Susan K.; Chi, Jen-Tsan

    2015-01-01

    Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine

  13. Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography

    SciTech Connect

    Mandal, Kalyaneswar; Uppalapati, Maruti; Ault-Riché, Dana; Kenney, John; Lowitz, Joshua; Sidhu, Sachdev S.; Kent, Stephen B.H.

    2012-10-23

    Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically synthesized D- and L- forms of the protein ligand showed reciprocal chiral specificity in surface plasmon resonance binding experiments: The L-protein ligand bound only to D-VEGF-A, whereas the D-protein ligand bound only to L-VEGF-A. The D-protein ligand, but not the L-protein ligand, inhibited the binding of natural VEGF{sub 165} to the VEGFR1 receptor. Racemic protein crystallography was used to determine the high resolution X-ray structure of the heterochiral complex consisting of {l_brace}D-protein antagonist + L-protein form of VEGF-A{r_brace}. Crystallization of a racemic mixture of these synthetic proteins in appropriate stoichiometry gave a racemic protein complex of more than 73 kDa containing six synthetic protein molecules. The structure of the complex was determined to a resolution of 1.6 {angstrom}. Detailed analysis of the interaction between the D-protein antagonist and the VEGF-A protein molecule showed that the binding interface comprised a contact surface area of approximately 800 {angstrom}{sup 2} in accord with our design objectives, and that the D-protein antagonist binds to the same region of VEGF-A that interacts with VEGFR1-domain 2.

  14. Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography.

    PubMed

    Mandal, Kalyaneswar; Uppalapati, Maruti; Ault-Riché, Dana; Kenney, John; Lowitz, Joshua; Sidhu, Sachdev S; Kent, Stephen B H

    2012-09-11

    Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically synthesized D- and L- forms of the protein ligand showed reciprocal chiral specificity in surface plasmon resonance binding experiments: The L-protein ligand bound only to D-VEGF-A, whereas the D-protein ligand bound only to L-VEGF-A. The D-protein ligand, but not the L-protein ligand, inhibited the binding of natural VEGF(165) to the VEGFR1 receptor. Racemic protein crystallography was used to determine the high resolution X-ray structure of the heterochiral complex consisting of {D-protein antagonist + L-protein form of VEGF-A}. Crystallization of a racemic mixture of these synthetic proteins in appropriate stoichiometry gave a racemic protein complex of more than 73 kDa containing six synthetic protein molecules. The structure of the complex was determined to a resolution of 1.6 Å. Detailed analysis of the interaction between the D-protein antagonist and the VEGF-A protein molecule showed that the binding interface comprised a contact surface area of approximately 800 Å(2) in accord with our design objectives, and that the D-protein antagonist binds to the same region of VEGF-A that interacts with VEGFR1-domain 2. PMID:22927390

  15. Enantioselective excited-state quenching of racemic Tb (III) and Eu (III) Tris (pyridine-2,6-dicarboxylate) by vitamin B 12 derivatives

    NASA Astrophysics Data System (ADS)

    Meskers, Stefan C. J.; Dekkers, Harry P. J. M.

    1999-08-01

    Enantioselectivity in the dynamic quenching of the luminescence of the Δ and Λ enantiomers of racemic Tb(III)(pyridine-2,6-dicarboxylate=DPA) 33- and Eu(DPA) 33- by a series of corrinoids is demonstrated by time resolved luminescence and circular-polarization-of-luminescence (CPL) spectroscopy. Studied are cyanocobalamin (vitamin B 12), aquacobalamin (B 12a) and its conjugated base hydroxocobalamin (HOCbl), dicyanocobinamide ((CN) 2Cbi) and the heptamethyl ester of dicyanocobyrinic acid ((CN) 2Cby(OMe) 7). For this set of quenchers (Q), the diastereomeric quenching rate constants ( kqΔ and kqΛ) are reported together with the degree of enantioselectivity Eq=( kqΔ- kqΛ)/( kqΔ+ kqΛ). In the systems with Tb, values of the average rate constant kqavg(=( kqΔ+ kqΛ)/2) are 1.0, 2.9 and 0.53 10 8 M -1 s -1 for CNCbl, (CN) 2Cbi, (CN) 2Cby(OMe) 7 with Eq=-0.24, -0.20, +0.01 (standard error of Eq is 0.01). The quenching by B 12a is strongly dependent on pH and ionic strength ( I); when I=12 mM we find kqavg=5.3, Eq=-0.23 at pH 6.7 and kqavg=1.3, Eq=-0.27 at pH 8.9. Corresponding rates for Eu are 0.41, 27, 3.4 10 7 M -1 s -1 and for B 12a, 7.3 and 1.2 10 7 M -1 s -1, corresponding values for Eq -0.27, -0.29, +0.02, -0.21 and -0.29. The quenching reaction is modeled as a pre-equilibrium involving the formation of an encounter complex (association constant K) followed by the actual electronic energy transfer step (rate ket). By relating the quenching data with molecular structure it is argued that the binding in the encounter complex involves two hydrogen bonds between the uncoordinated carboxylate oxygen atom of two DPA ligands of Ln(DPA) 33- and two amide groups of the corrinoid, presumably involving the a and g, the a and b, or the b and g side chains. For some corrinoid/Ln(DPA) 33- complexes the association constants and enantioselectivities in the ground state are known (Spectrochimica Acta 55A (1999) 1837-1855), which allows for an estimate of the average rate of

  16. Stimulatory effect of isoferulic acid on alpha1A-adrenoceptor to increase glucose uptake into cultured myoblast C2C12 cell of mice.

    PubMed

    Liu, I M; Tsai, C C; Lai, T Y; Cheng, J T

    2001-05-14

    In an attempt to elucidate the effect of isoferulic acid on alpha1-adrenoceptor (AR), the myoblast C2C12 cells of mice were employed to investigate the change of glucose uptake in the present study. Isoferulic acid enhanced the uptake of radioactive glucose into C2C12 cells in a concentration-dependent manner, which were abolished by pretreatment with prazosin. Effect of isoferulic acid on alpha1-AR was further characterized using the displacement of [3H]YM617 binding in C2C12 cells. The radioactive glucose uptake increasing action of isoferulic acid was abolished by tamsulosin or WB 4101 at concentration sufficient to block alpha1A-adrenoceptor (alpha1A-AR) but it was not modified by chlorethylclonidine (CEC) at the concentration sufficient to abolish alpha1B-AR. An activation of alpha1A-AR by isoferulic acid in C2C12 cells can thus be considered. Pharmacological inhibition of phospholipase C (PLC) by U73312 resulted in a concentration-dependent reduction of isoferulic acid-stimulated glucose uptake in C2C12 cells. This inhibition by U73112 was specific because the inactive congener, U73343, failed to modify the action of isoferulic acid. Also, chelerythrine and GF 109203X diminished the action of isoferulic acid at concentration sufficient to inhibit the activity of protein kinase C (PKC). The obtained data suggest that an activation of alpha1A-AR by isoferulic acid may increase the glucose uptake via PLC-PKC pathway in C2C12 cells. PMID:11474559

  17. Determining D/L Ratios of Amino Acids Found in Ice Above Lake Vostok Using ESI/CIT Mass Spectroscopy

    NASA Technical Reports Server (NTRS)

    Tsapin, A.; Kanik, I.; Beegle, L. W.; Wu, L.; Cooks, R. G.

    2003-01-01

    Astrobiology is an area where longevity of (micro) organisms is of great interest. Cryospheres are common phenomena in the solar system, particularly on satellites, comets and asteroids, as well as at least some of the planets. Recent data from the Mars Global Surveyor mission suggest the possibility of permafrost or perhaps even liquid water under the Martian surface [2]. These environments may be the areas in which the probability of finding life is the highest. This issue is of concern due to the probable evolution of planetary environments such as that of Mars from more hospitable to less hospitable conditions over the history of the solar system. In addition, evaluation of the possible transfer of living organisms between planets via impact ejecta [3] is dependent on knowledge of the maximum time periods over which microorganisms can remain dormant and subsequently revive and reproduce.Amino acid racemization dating, or aminostratigraphy, has been used for many years to date biological systems, and has been examined as a possible biosignature detection technique for Mars. We have suggested using amino acid racemization as one of the most indicative biosignatures [4]. Only life systems produce preferential synthesis of L-amino acids versus D-amino acids. Almost all amino acids in terrestrial organisms can be found only in the L-enantiomeric form.We studied the level of amino acid racemization, specifically of aspartic acid, in permafrost samples from eastern Siberia. Also we analyzed samples of ice from borehole drilled to lake Vostok, Antarctica.

  18. Distribution and inferred age of exfoliation joints in the Aar Granite of the central Swiss Alps and relationship to Quaternary landscape evolution

    NASA Astrophysics Data System (ADS)

    Ziegler, Martin; Loew, Simon; Moore, Jeffrey R.

    2013-11-01

    deepest exfoliation joint generation is associated with erosion of the inner glacial troughs of the upper Aar valley, which likely occurred during the mid-Pleistocene Revolution. Our study shows how exfoliation joint episodes can be dated, and, conversely, that better knowledge of the distribution of exfoliation joint sets can reveal unique information about the morphological evolution of an Alpine valley.

  19. The prebiotic synthesis of amino acids - interstellar vs. atmospheric mechanisms

    NASA Astrophysics Data System (ADS)

    Meierhenrich, U. J.; Muñoz Caro, G. M.; Schutte, W. A.; Barbier, B.; Arcones Segovia, A.; Rosenbauer, H.; Thiemann, W. H.-P.; Brack, A.

    2002-11-01

    Until very recently, prebiotic amino acids were believed to have been generated in the atmosphere of the early Earth, as successfully simulated by the Urey-Miller experiments. Two independent studies now identified ice photochemistry in the interstellar medium as a possible source of prebiotic amino acids. Ultraviolet irradiation of ice mixtures containing identified interstellar molecules (such as H2O, CO2, CO, CH3OH, and NH3) in the conditions of vacuum and low temperature found in the interstellar medium generated amino acid structures including glycine, alanine, serine, valine, proline, and aspartic acid. After warmup, hydrolysis and derivatization, our team was able to identify 16 amino acids as well as furans and pyrroles. Enantioselective analyses of the amino acids showed racemic mixtures. A prebiotic interstellar origin of amino acid structures is now discussed to be a plausible alternative to the Urey-Miller mechanism.

  20. Nonsteroidal antiinflammatory agents. Part 16: Stereomeric 3-aryl-biphenylyl-hydroxy-propionic acids.

    PubMed

    Guarnieri, A; Burnelli, S; Varoli, L; Ghedini, N; Scapini, G; Ferri, S; Cavicchini, E

    1985-08-01

    As part of a wider research project on structure-activity relationships of chiral arylalkanoic acids, stereomeric aryl- biphenylyl-hydroxypropionic acids 3a-d have been prepared and their antiinflammatory activity evaluated. Diastereomeric racemic erythro- and threo-acids have been synthesized by reaction of alpha-lithiated biphenylyl-acetic acid salts with the appropriate aldehyde. They were separated, and after attribution of their relative configuration by 1H-NMR analysis, resolved. The antiinflammatory activities of the enantiomeric potassium salts were determined by the carrageenan test. PMID:4080796

  1. Thermal synthesis and hydrolysis of polyglyceric acid. [in orgin of life studying

    NASA Technical Reports Server (NTRS)

    Weber, Arthur L.

    1989-01-01

    Polyglyceric acid was synthesized by thermal condensation of glyceric acid at 80 C in the presence and absence of two mole percent of sulfuric acid catalyst. The acid catalyst accelerated the polymerization over 100-fold and made possible the synthesis of insoluble polymers of both L- and DL-glyceric acid by heating for less than 1 day. Racemization of L-glyceric acid yielded less than 1 percent D-glyceric acid in condensations carried out at 80 C with catalyst for 1 day and without catalyst for 12 days. The condensation of L-glyceric acid yielded an insoluble polymer much more readily than condensation of DL-glyceric acid. Studies of the hydrolysis of poly-DL-glyceric acid revealed that it was considerably more stable under mild acidic conditions compared to neutral pH. The relationship of this study to the origin of life is discussed.

  2. Bacterial defluorination of 4-fluoroglutamic acid.

    PubMed

    Donnelly, Clár; Murphy, Cormac D

    2007-12-01

    Fluorinated amino acids are used as enzyme inhibitors, mechanistic probes and in the production of pharmacologically active peptides. Because enantiomerically pure 4-fluoroglutamate is difficult to prepare, the selective degradation of the L-isomer is a potentially convenient method of obtaining D-4-fluoroglutamate from the racemate. In this paper, we describe our investigations on the degradation of 4-fluoroglutamate by bacteria. Fluoride ion was detected in resting-cell cultures of a number of bacteria that were incubated with racemic 4-fluoroglutamate. Analysis of the culture supernatants by chiral gas chromatography-mass spectrometry revealed that only the L-isomer was degraded. The degradation of 4-fluoroglutamate was also examined in cell-free extracts of Streptomyces cattleya and Proteus mirabilis, and it was observed that equimolar concentrations of fluoride ion and ammonia were generated. The activity was located in the soluble fraction of cell extracts, thus is not related to the L-2-amino-4-chloro-4-pentenoic acid dehydrochlorinase previously identified in membrane fractions of P. mirabilis. PMID:17901951

  3. Z-Selective Hydrothiolation of Racemic 1,3-Disubstituted Allenes: An Atom-Economic Rhodium-Catalyzed Dynamic Kinetic Resolution.

    PubMed

    Pritzius, Adrian B; Breit, Bernhard

    2015-12-21

    A Z-selective rhodium-catalyzed hydrothiolation of 1,3-disubstituted allenes and subsequent oxidation towards the corresponding allylic sulfones is described. Using the bidentate 1,4-bis(diphenylphosphino)butane (dppb) ligand, Z/E-selectivities up to >99:1 were obtained. The highly atom-economic desymmetrization reaction tolerates functionalized aromatic and aliphatic thiols. Additionally, a variety of symmetric internal allenes, as well as unsymmetrically disubstituted substrates were well tolerated, thus resulting in high regioselectivities. Starting from chiral but racemic 1,3-disubstituted allenes a dynamic kinetic resolution (DKR) could be achieved by applying (S,S)-Me-DuPhos as the chiral ligand. The desired Z-allylic sulfones were obtained in high yields and enantioselectivities up to 96 % ee. PMID:26418035

  4. Crystallization of Enantiomerically Pure Proteins from Quasi-Racemic Mixtures: Structure Determination by X-Ray Diffraction of Isotope-Labeled Ester Insulin and Human Insulin.

    PubMed

    Mandal, Kalyaneswar; Dhayalan, Balamurugan; Avital-Shmilovici, Michal; Tokmakoff, Andrei; Kent, Stephen B H

    2016-03-01

    As a part of a program aimed towards the study of the dynamics of human insulin-protein dimer formation using two-dimensional infrared spectroscopy, we used total chemical synthesis to prepare stable isotope labeled [(1-(13) C=(18) O)Phe(B24) )] human insulin, via [(1-(13) C=(18) O)Phe(B24) )] ester insulin as a key intermediate product that facilitates folding of the synthetic protein molecule (see preceding article). Here, we describe the crystal structure of the synthetic isotope-labeled ester insulin intermediate and the product synthetic human insulin. Additionally, we present our observations on hexamer formation with these two proteins in the absence of phenol derivatives and/or Zn metal ions. We also describe and discuss the fractional crystallization of quasi-racemic protein mixtures containing each of these two synthetic proteins. PMID:26707939

  5. Geochemistry of amino acids in shells of the clam Saxidomus

    USGS Publications Warehouse

    Kvenvolden, K.A.; Blunt, D.J.; McMenamin, M.A.; Straham, S.E.

    1980-01-01

    Concentrations of amino acids and their corresponding d l enantiomeric ratios have been measured in shells of the bivalve mollusk Saxidomus from eleven localities, ranging in age from modern to probably more than 500,000 yr, along the Pacific coast of North America. Natural logarithms of amino acid concentrations correlate well with d l ratios, and the relationship provides a possible guide to the selection of fossils for use in amino acid dating. The relative order of the extents of racemization of amino acids at any given time appears to change with increasing sample age. Application of the amino acid dating method to shells from Whidbey Island, Washington, yields an age of about 80,000 yr, in contrast to the previously determined radiocarbon age of 36,000 yr which was measured on some shell carbonate and considered a minimum age. The amino acid age is compatible with the geologic record in the area. ?? 1980.

  6. Selective inhibition of human immunodeficiency viruses by racemates and enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine.

    PubMed Central

    Schinazi, R F; McMillan, A; Cannon, D; Mathis, R; Lloyd, R M; Peck, A; Sommadossi, J P; St Clair, M; Wilson, J; Furman, P A

    1992-01-01

    2',3'-Dideoxy-5-fluoro-3'-thiacytidine (FTC) has been shown to be a potent and selective compound against human immunodeficiency virus type 1 in acutely infected primary human lymphocytes. FTC is also active against human immunodeficiency virus type 2, simian immunodeficiency virus, and feline immunodeficiency virus in various cell culture systems, including human monocytes. The antiviral activity can be prevented by 2'-deoxycytidine, but not by other natural nucleosides, suggesting that FTC must be phosphorylated to be active and 2'-deoxycytidine kinase is responsible for the phosphorylation. By using chiral columns or enzymatic techniques, the two enantiomers of FTC were separated. The (-)-beta-enantiomer of FTC was about 20-fold more potent than the (+)-beta-enantiomer against human immunodeficiency virus type 1 in peripheral blood mononuclear cells and was also effective in thymidine kinase-deficient CEM cells. Racemic FTC and its enantiomers were nontoxic to human lymphocytes and other cell lines at concentrations of up to 100 microM. Studies with human bone marrow cells indicated that racemic FTC and its (-)-enantiomer had a median inhibitory concentration of > 30 microM. The (+)-enantiomer was significantly more toxic than the (-)-enantiomer to myeloid progenitor cells. The susceptibilities to FTC of pretherapy isolates in comparison with those of posttherapy 3'-azido-3'-deoxythymidine-resistant viruses in human lymphocytes were not substantially different. Similar results were obtained with well-defined 2',3'-dideoxyinosine- and nevirapine-resistant viruses. (-)-FTC-5'-triphosphate competitively inhibited human immunodeficiency virus type 1 reverse transcriptase, with an inhibition constant of 2.9 microM, when a poly(I)n.oligo(dC)19-24 template primer was used. These results suggest that further development of the (-)-Beta-enantiomer of FTC is warranted as an antiviral agent for infections caused by human immunodeficiency viruses. Images PMID:1283296

  7. (2RS,8aRS)-6-Oxo-1,2,3,4,6,7,8,8a-octa­hydro­naphthalene-2-carboxylic acid

    PubMed Central

    Efthimiopoulos, Georgia; Lalancette, Roger A.; Thompson, Hugh W.

    2008-01-01

    The title racemate, C11H14O3, aggregates in the crystal structure as acid-to-ketone O—H⋯O hydrogen-bonding catemers whose components are glide-related. The relative stereochemistry at the carboxyl group arises spontaneously during the synthesis. Two inter­molecular C—H⋯O=C close contacts were found, both involving the acid group. PMID:21581270

  8. Separation of octopamine racemate on (R,S)-2-amino-1-phenylethanol imprinted polymer--Experimental and computational studies.

    PubMed

    Sobiech, Monika; Żołek, Teresa; Luliński, Piotr; Maciejewska, Dorota

    2016-01-01

    Ten molecularly imprinted polymers coded as MIP1-MIP10 were prepared by the radical bulk polymerization using (R,S)-(±)-2-amino-1-phenylethanol as the structural analog of the target analyte (R,S)-octopamine. The functional monomers, 4-vinylbenzoic acid (1), methacrylic acid (2), acrylic acid (3), trifluoromethacrylic acid (4), itaconic acid (5), acrylamide (6), isopropenylbenzene (7), 2-hydroxyethyl methacrylate (8), 2-(diethylamino)ethyl methacrylate (9), allylamine (10) were polymerized consecutively with the ethylene glycol dimethacrylate cross-linker in methanol as the porogen. On the basis of the binding capacity of (R,S)-octopamine MIP1 with affinity factor equal to 6.37 was selected for further analysis. The affinity of polymer matrix MIP1 was tested by the non-competitive binding experiments of eight structurally related analytes. Finally, molecularly imprinted solid phase extraction (MISPE) of (R,S)-octopamine from spiked human serum albumin was carried out in order to verify the applicability of novel sorbent. The molecular modeling was employed to rationalize the stereodifferentiation of the analytes by the stereospecific sites formed in the polymer matrix. PMID:26695304

  9. Asymmetric Reduction of Lactam-Based β-Aminoacrylates. Synthesis of Heterocyclic β(2)-Amino Acids.

    PubMed

    Campello, Hugo Rego; Parker, Jeremy; Perry, Matthew; Ryberg, Per; Gallagher, Timothy

    2016-08-19

    The ability to affect asymmetric reduction of heterocyclic β-aminoacrylates 1 (n = 1-3) has been assessed with pyrrolidine and piperidone variants generating the corresponding N-heterocyclic β(2)-amino acids 3b and 5b with high enantioselectivity (≥97% ee) using a Rh/WALPHOS catalyst combination. The use of the carboxylic acid substrate was essential; the corresponding esters do undergo reduction but led to racemic products. The seven-ring azepanone variant (as the carboxylic acid 9b) underwent reduction, but only a minimal level of asymmetric induction was observed. PMID:27508307

  10. Kinetic resolution of acids in acylation reactions in the presence of chiral tertiary amines

    SciTech Connect

    Potapov, V.M.; Dem'yanovich, V.M.; Khlebnikov, V.A.

    1988-07-10

    Asymmetric synthesis has now become an important method for the production of optically active compounds, and its most attractive form is asymmetric catalysis. This work was devoted to an investigation into asymmetric catalysis with chiral tertiary amines in acylation reactions. During the acylation of alcohols and amines by the action of racemic 2-phenylpropionic and 2-methyl-3-phenylpropionic acids in the presence of S-nicotine the initial acids are resolved kinetically. The (R)-2-phenylpropionic acid obtained in this way had an optical purity of 0.5-1.5%.

  11. Enantioselective Metabolism of Chiral 3-Phenylbutyric Acid, an Intermediate of Linear Alkylbenzene Degradation, by Rhodococcus rhodochrous PB1

    PubMed Central

    Simoni, S.; Klinke, S.; Zipper, C.; Angst, W.; Kohler, H. E.

    1996-01-01

    Rhodococcus rhodochrous PB1 was isolated from compost soil by selective culture with racemic 3-phenylbutyric acid as the sole carbon and energy source. Growth experiments with the single pure enantiomers as well as with the racemate showed that only one of the two enantiomers, (R)-3-phenylbutyric acid, supported growth of strain PB1. Nevertheless, (S)-3-phenylbutyric acid was cometabolically transformed to, presumably, (S)-3-(2,3-dihydroxyphenyl)butyric acid (the absolute configuration at the C-3 atom is not known yet) by (R)-3-phenylbutyric acid-grown cells of strain PB1, as shown by (sup1)H nuclear magnetic resonance spectroscopy of the partially purified compound and gas chromatography-mass spectrometry analysis of the trimethylsilyl derivative. Oxygen uptake rates suggest that either 3-phenylpropionic acid or cinnamic acid (trans-3-phenyl-2-propenoic acid) is the substrate for aromatic ring hydroxylation. This view is substantiated by the fact that 3-(2,3-dihydroxyphenyl)propionic acid was a substrate for meta cleavage in cell extracts of (R)-3-phenylbutyric acid-grown cells of strain PB1. Gas chromatography-mass spectrometry analysis of trimethylsilane-treated ethyl acetate extracts of incubation mixtures showed that both the meta-cleavage product, 2-hydroxy-6-oxo-2,4-nonadiene-1,9-dicarboxylic acid, and succinate, a hydrolysis product thereof, were formed during such incubations. PMID:16535265

  12. Polymerization of amino acids containing nucleotide bases

    NASA Technical Reports Server (NTRS)

    Ben Cheikh, Azzouz; Orgel, Leslie E.

    1990-01-01

    The nucleoamino acids 1-(3'-amino,3'-carboxypropyl)uracil (3) and 9-(3'-amino,3'-carboxypropyl)adenine (4) have been prepared as (L)-en-antiomers and as racemic mixtures. When 3 or 4 is suspended in water and treated with N,N'-carbon-yldiimidazole, peptides are formed in good yield. The products formed from the (L)-enantiomers are hydrolyzed to the monomeric amino acids by pronase. Attempts to improve the efficiency of these oligomerizations by including a polyuridylate template in the reaction mixture were not successful. Similarly, oligomers derived from the (L)-enantiomer of 3 did not act as templates to facilitate the oligomerization of 4.

  13. The Next Generation MOD: A Microchip Amino Acid Analyzer for Detecting Extraterrestrial Life

    NASA Technical Reports Server (NTRS)

    Mathies, R. A.; Hutt, L. D.; Bada, J. L.; Glavin, D.; Grunthaner, F. J.; Grunthaner, P. J.

    2000-01-01

    The MOD (Mars Organic Detector) instrument which has selected for the definition phase of the BEDS package on the 2005 Mars Explorer Program spacecraft is designed to simply detect the presence of amino acids in Martian surface samples at a sensitivity of a few parts per billion (ppb). An additional important aspect of amino acid analyses of Martian samples is identifying and quantifying which compounds are present, and also distinguishing those produced abiotically from those synthesized by either extinct or extant life. Amino acid homochirality provides an unambiguous way of distinguishing between abiotic vs. biotic origins. Proteins made up of mixed D- and L-amino acids would not likely have been efficient catalysts in early organisms because they could not fold into bioactive configurations such as the a-helix. However, enzymes made up of all D-amino acids function just as well as those made up of only L-amino acids, but the two enzymes use the opposite stereoisomeric substrates. There are no biochemical reasons why L-amino acids would be favored over Damino acids. On Earth, the use of only L-amino acids in proteins by life is probably simply a matter of chance. We assume that if proteins and enzymes were a component of extinct or extant life on Mars, then amino acid homochirality would have been a requirement. However, the possibility that Martian life was (or is) based on D-amino acids would be equal to that based on L-amino acids. The detection of a nonracemic mixture of amino acids in a Martian sample would be strong evidence for the presence of an extinct or extant biota on Mars. The finding of an excess of D-amino acids would provide irrefutable evidence of unique Martian life that could not have been derived from seeding the planet with terrestrial life (or the seeding of the Earth with Martian life). In contrast, the presence of racemic amino acids, along with non-protein amino acids such as alpha-aminoisobutyric acid and isovaline, would be indicative

  14. The influence of snow cover on alpine floods reconstructed from the analysis of satellite images. The case of the Hasli-Aare river basin, Berner Oberland (1987-2012)

    NASA Astrophysics Data System (ADS)

    Cabrera-Medina, Paula; Schulte, Lothar; Carvalho, Filipe; Peña, Juan Carlos; García, Carles

    2016-04-01

    Regarding the hydrological hazards in the Hasli-Aare river over the last century, instrumental and documentary data show that flood frequency and magnitude increased since 1977. One of the main water inputs contributing to peak discharges is given by the thaw of the stored snow. Therefore, the knowledge of the evolution of snow cover is considered essential for the assessment of alpine floods. Snow cover studies can be made by different approaches such as the analysis of data provided by field work or by nivometeorological stations. However, these methods are usually expensive and do not present adequate spatial or temporal coverage data. For this reason, satellite images with different spatial and temporal resolution are an interesting complementary source for the understanding of the snow cover dynamics. The aim of the paper is to study the influence of snow cover variations during years of severe floods that occurred in the upper Aare basin from 1987 to 2012. Three satellite images have been selected for each of the 9 studied events: 1) maximum snow cover during winter, 2) the last image before the event and 3) the first image after the flood. Each image has been processed with the ArcGIS software applying a statistical method of supervised classification. This image processing allows the spatial quantification of the variation of the snow cover in the Aare headwater catchment. Because the melting of snow cover is related to the changes of weather situations before and during the flood episode, it is important to analyse also the nivometeorological data of stations located in the catchment (snow depth, temperature and precipitation). From these data we determined 4 types of flood, which can be classified according to their nivometeorological variables and synoptic situation (500 hPa geopotential and Sea Level Pressure) into two patterns. The first group of events can be associated to an Atlantic pattern recording decreasing temperatures, moderate to high

  15. Nicotinic acid metabolism. 2,3-Dimethylmalate lyase.

    PubMed

    Pirzer, P; Lill, U; Eggerer, H

    1979-12-01

    1) A new enzyme, 2,3-dimethylmalate lyase, was purified from Clostridium barkeri to about 80% homogeneity. Some of the properties of the enzyme are described. 2) It is shown that the 2,3-dimethylmalic acid (m.p. 143 degrees C) described in the literature represents only one racemic pair. This pair is not attacked by 2,3-dimethylmalate lyase. 3) The isolation of both racemic pairs of 2,3-dimethylmalic acid is described. Half of one pair, m.p. 104-106 degrees C, was converted to propionate and pyruvate by 2,3-dimethylmalate lyase. 4) In combination with earlier work performed by E.R. Stadtman and coworkers the results given under points 1--3 establish 2,3-dimethylmalate as an intermediate in the degradation of nicotinic acid by C. barkeri. 5) Experimental evidence indicates the 2,3-dimethylmalate lyase is no acyl-S-enzyme and that it is different in this respect as well as in quaternary structure from the apparently related enzymes citrate lyase and citramalate lyase. PMID:527937

  16. The radiolysis and radioracemization of amino acids on silica surfaces

    NASA Technical Reports Server (NTRS)

    Bonner, W. A.; Lemmon, R. M.

    1981-01-01

    Results are presented of experiments on the radioracemization of amino acids in the presence of silica surfaces such as may have been found on the prebiotic earth. L-leucine and a DL-leucine mixture deposited on samples of 1-quartz and an amorphous silica preparation (Syloid 63) was subjected to Co-60 gamma-ray irradiation, then analyzed by gas chromatography to determine the radiolysis and racemization rates. The quartz surface is found to have a marginal efficacy in enhancing radiolysis when compared with a crystalline L-leucine control, although enhancing radioracemization symmetrically by a factor of two. Both the radiolysis and radioracemization of L-leucine and DL-leucine on a Syloid-63 silica surface are observed to increase with increasing radiation dose, and to be substantially greater than in the crystalline controls. Additional experiments with the nonprotein amino acid isovaline deposited on Syloid 63 confirm the greater radiolysis susceptibility of amino acids deposited on silica with respect to the crystalline state, although racemization is not observed. The observations suggest that the presence of a silica surface would have a deleterious effect on any mechanism for the origin of molecular chirality relying on stereoselective beta-radiolysis.

  17. Highly Stereocontrolled Ring-Opening Polymerization of Racemic Alkyl β-Malolactonates Mediated by Yttrium [Amino-alkoxy-bis(phenolate)] Complexes.

    PubMed

    Jaffredo, Cédric G; Chapurina, Yulia; Kirillov, Evgueni; Carpentier, Jean-François; Guillaume, Sophie M

    2016-05-23

    Yttrium [amino-alkoxy-bis(phenolate)]amido complexes have been used for the ring-opening polymerization (ROP) of racemic alkyl β-malolactonates (4-alkoxycarbonyl-2-oxetanones, rac-MLA(R) s) bearing an allyl (All), benzyl (Bz) or methyl (Me) lateral ester function. The nature of the ortho-substituent on the phenolate rings in the metal ancillary dictated the stereocontrol of the ROP, and consequently the syndiotactic enrichment of the resulting polyesters. ROP promoted by catalysts with halogen (Cl, Br)-disubstituted ligands allowed the first reported synthesis of highly syndiotactic PMLA(R) s (Pr ≥ 0.95); conversely, catalysts bearing bulky alkyl and aryl ortho-substituted ligands proved largely ineffective. All polymers have been characterized by (1) H and (13) C{(1) H} NMR spectroscopy, MALDI-ToF mass spectrometry and DSC analyses. Statistical and thermal analyses enabled the rationalization of the chain-end control mechanism. Whereas the stereocontrol of the polymerization obeyed a Markov first-order (Mk1) model for the ROP of rac-MLA(Bz) and rac-MLA(All) , the ROP of rac-MLA(Me) led to a chain end-control of Markov second-order type (Mk2). DFT computations suggest that the high stereocontrol ability featured by catalysts bearing Cl- and Br-substituted ligands does not likely originate from halogen bonding between the halogen substituent and the growing polyester chain. PMID:27080758

  18. Enhanced production of Penicillium expansum PED-03 lipase through control of culture conditions and application of the crude enzyme in kinetic resolution of racemic Allethrolone.

    PubMed

    Dai, Dazhang; Xia, Liming

    2005-01-01

    Alkaline lipase production was performed in submerged fermentation by Penicillium expansum PED-03. It was found that the suitable carbon source and nitrogen source for lipase production were 0.5% starch and 4.0% soybean meal, respectively. The maximal lipase activity (850 U/mL) of production was achieved at initial pH 5.5-6.0, 26 degrees C, 72 h. Tween-80 was an effective enhancer for lipase production. Agitation speed of the fermentor played an important role, and the suitable agitation speed for lipase production was 500 r/min. The lipase was stable within the range of pH 7.0-10.0 and 20-40 degrees C, and the optimum conditions for the enzymatic reaction were 35 degrees C and pH 9.5. The enzymatic resolution of racemic allethrolone (4-hydroxy-3-methyl-2-(2-propenyl)-2- cyclopenten-1-one) was carried out by the lipase from P. expansum PED-03, and the conversion reached 48% with excellent enantioselectivity (E > 100), which showed a good application potential in the production of optically pure allethrolone. PMID:16080697

  19. Responsive organogels formed by supramolecular self assembly of PEG-block-allyl-functionalized racemic polypeptides into β-sheet-driven polymeric ribbons†

    PubMed Central

    Zou, Jiong; Zhang, Fuwu; Chen, Yingchao; Raymond, Jeffery E.; Zhang, Shiyi; Fan, Jingwei; Zhu, Jiahua; Li, Ang; Seetho, Kellie; He, Xun; Pochan, Darrin J.

    2014-01-01

    A chemically reactive hybrid diblock polypeptide gelator poly(ethylene glycol)-block-poly(dl-allylglycine) (PEG-b-PDLAG) is an exceptional material, due to the characteristics of thermo-reversible organogel formation driven by the combination of a hydrophilic polymer chain linked to a racemic oligomeric homopeptide segment in a range of organic solvents. One-dimensional stacking of the block copolymers is demonstrated by ATR-FTIR spectroscopy, wide-angle X-ray scattering to be driven by the supramolecular assembly of β-sheets in peptide blocks to afford well-defined fiber-like structures, resulting in gelation. These supramolecular interactions are sufficiently strong to achieve ultra low critical gelation concentrations (ca. 0.1 wt%) in N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and methanol. The critical gel transition temperature was directly proportional to the polymer concentration, so that at low concentrations, thermoreversibility of gelation was observed. Dynamic mechanical analysis studies were employed to determine the organogel mechanical properties, having storage moduli of ca. 15.1 kPa at room temperature. PMID:25788968

  20. Identification of diamino acids in the Murchison meteorite

    PubMed Central

    Meierhenrich, Uwe J.; Muñoz Caro, Guillermo M.; Bredehöft, Jan Hendrik; Jessberger, Elmar K.; Thiemann, Wolfram H.-P.

    2004-01-01

    Amino acids identified in the Murchison chondritic meteorite by molecular and isotopic analysis are thought to have been delivered to the early Earth by asteroids, comets, and interplanetary dust particles where they may have triggered the appearance of life by assisting in the synthesis of proteins via prebiotic polycondensation reactions [Oró, J. (1961) Nature 190, 389–390; Chyba, C. F. & Sagan, C. (1992) Nature 355, 125–132]. We report the identification of diamino acids in the Murchison meteorite by new enantioselective GC-MS analyses. dl-2,3-diaminopropanoic acid, dl-2,4-diaminobutanoic acid, 4,4′-diaminoisopentanoic acid, 3,3′-diaminoisobutanoic acid, and 2,3-diaminobutanoic acid were detected in the parts per billion range after chemical transformation into N,N-diethoxycarbonyl ethyl ester derivatives. The chiral diamino acids show a racemic ratio. Laboratory data indicate that diamino acids support the formation of polypeptide structures under primitive Earth conditions [Brack, A. & Orgel, L. E. (1975) Nature 256, 383–387] and suggest polycondensation reactions of diamino acids into early peptide nucleic acid material as one feasible pathway for the prebiotic evolution of DNA and RNA genomes [Joyce, G. F. (2002) Nature 418, 214–221]. The results obtained in this study favor the assumption that not only amino acids (as the required monomers of proteins) form in interstellar/circumstellar environments, but also the family of diamino monocarboxylic acids, which might have been relevant in prebiotic chemistry. PMID:15194825

  1. Identification of diamino acids in the Murchison meteorite

    NASA Astrophysics Data System (ADS)

    Meierhenrich, Uwe J.; Muñoz Caro, Guillermo M.; Hendrik Bredehöft, Jan; Jessberger, Elmar K.; Thiemann, Wolfram H.-P.

    Amino acids identified in the Murchison chondritic meteorite by molecular and isotopic analysis are thought to have been delivered to the early Earth by asteroids, comets, and interplanetary dust particles where they may have triggered the appearance of life by assisting in the synthesis of proteins via prebiotic polycondensation reactions [Oró, J. (1961) Nature 190, 389-390; Chyba, C. F. & Sagan, C. (1992) Nature 355, 125-132]. We report the identification of diamino acids in the Murchison meteorite by new enantioselective GC-MS analyses. DL-2,3-diaminopropanoic acid, DL-2,4-diaminobutanoic acid, 4,4'-diaminoisopentanoic acid, 3,3'-diaminoisobutanoic acid, and 2,3-diaminobutanoic acid were detected in the parts per billion range after chemical transformation into N,N-diethoxycarbonyl ethyl ester derivatives. The chiral diamino acids show a racemic ratio. Laboratory data indicate that diamino acids support the formation of polypeptide structures under primitive Earth conditions [Brack, A. & Orgel, L. E. (1975) Nature 256, 383-387] and suggest polycondensation reactions of diamino acids into early peptide nucleic acid material as one feasible pathway for the prebiotic evolution of DNA and RNA genomes [Joyce, G. F. (2002) Nature 418, 214-221]. The results obtained in this study favor the assumption that not only amino acids (as the required monomers of proteins) form in interstellar/circumstellar environments, but also the family of diamino monocarboxylic acids, which might have been relevant in prebiotic chemistry.

  2. Extraterrestrial Amino Acids in Orgueil and Ivuna: Tracing the Parent Body of CI Type Carbonaceous Chondrites

    NASA Technical Reports Server (NTRS)

    Meyer, Michael (Technical Monitor); Ehrenfreund, Pascale; Glavin, Daniel P.; Bota, Oliver; Cooper, George; Bada, Jeffrey

    2001-01-01

    Amino acid analyses using HPLC of pristine interior pieces of the CI carbonaceous chondrites Orgueil and Ivuna have found that beta-alanine, glycine, and gamma-amino-n-butyric acid (ABA) are the most abundant amino acids in these two meteorites, with concentrations ranging from approx. 600 to 2,000 parts per billion (ppb). Other alpha-amino acids such as alanine, alpha-ABA, alpha-aminoisobutyric acid (AIB), and isovaline are present only in trace amounts (less than 200 ppb). Carbon isotopic measurements of beta-alanine and glycine and the presence of racemic (D/L 1) alanine and beta-ABA in Orgueil suggest that these amino acids are extraterrestrial in origin. In comparison to the CM carbonaceous chondrites Murchison and Murray, the amino acid composition of the CIs is strikingly distinct, suggesting that these meteorites came from a different type of parent body, possibly an extinct comet, than did the CM carbonaceous chondrites.

  3. Amino Acids from Icy Amines: A Radiation-Chemical Approach to Extraterrestrial Synthesis

    NASA Technical Reports Server (NTRS)

    Dworkin, J. P.; Moore, M. H.

    2010-01-01

    Detections of amino acids in meteorites go back several decades, with at least 100 such compounds being reported for the Murchison meteorite alone. The presence of these extraterrestrial molecules raises questions as to their formation, abundance, thermal stability, racemization, and possible subsequent reactions. Although all of these topics have been studied in laboratories, such work often involves many variables and unknowns. This has led us to seek out model systems with which to uncover reaction products, test chemical predictions, and sited light on underlying reaction mechanisms. This presentation will describe one such study, focusing on amino-acid formation in ices.

  4. Immobilized β-cyclodextrin-based silica vs polymer monoliths for chiral nano liquid chromatographic separation of racemates.

    PubMed

    Ghanem, Ashraf; Ahmed, Marwa; Ishii, Hideaki; Ikegami, Tohru

    2015-01-01

    The enantioselectivity of immobilized β-cyclodextrin phenyl carbamate-based silica monolithic capillary columns was compared to our previously described polymer counterpart. 2,3,6-Tris(phenylcarbamoyl)-β-cyclodextrin-6-methacrylate was used as a functional monomer for the preparation of β-cyclodextrin (β-CD)-based silica and polymer monoliths. The silica monoliths were prepared via the sol-gel technique in fused silica capillary followed by modification of the bare silica monoliths with an anchor group prior to polymerization with β-CD methacrylate using either 2,2'-azobis(isobutyronitrile) or benzoylperoxide as radical initiators. On the other hand, the polymer monoliths were prepared via the copolymerization of β-CD methacrylate and ethylene glycol dimethacrylate in different ratios in situ in fused silica capillary. The prepared silica/polymer monoliths were investigated for the chiral separation of different classes of pharmaceuticals namely; α- and β-blockers, anti-inflammatory drugs, antifungal drugs, dopamine antagonists, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, diuretics, antihistaminics, anticancer drugs and antiarrhythmic drugs. Baseline separation was achieved for alprenolol, bufuralol, carbuterol, cizolertine, desmethylcizolertine, eticlopride, ifosfamide, 1-indanol, propranolol, tebuconazole, tertatolol and o-methoxymandelic acid under reversed phase conditions using mobile phase composed of methanol and water. The silica-based monoliths showed a comparative enantioselectivity to the polymer monoliths. PMID:25476312

  5. Efficient optical resolution of amino acid by alanine racemaze chiral analogue supported on mesoporous carbon

    NASA Astrophysics Data System (ADS)

    Jang, D.; Kim, K.; Park, D.; Kim, G.

    2012-09-01

    Optically pure D-amino acids are industrially important chiral building blocks for the synthesis of pharmaceuticals, food ingredients, and drug intermediates. Chemoenzymatic dynamic kinetic-resolution processes have recently been developed for deracemization of amino acids. S-ARCA would be a good candidate for the selective adsorption of D amino acid through the imine formation reaction. The organic phase containing S-ARCA adsorbent, TPPC or Ionic Liquid (as a phase transfer catalyst) in MC were coated on the surfaces of mesoporous carbon C-SBA-15(CMK). The aqueous solution of racemic D/L-amino acid and NaOH were added to the carbon support coated with ARCA. The D/L ratios on ARCA and in solution were determined with increasing reaction time. S-ARCA has a unique property for the selective adsorption of D- amino acid (up to 90% selcetivity) in the racemic mixture. The fixed bed reactor containing ARCA/carbon support was also adopted successfully for the selective separation of amino acid.

  6. Enrichment of Non-Terrestrial L-Proteinogenic Amino Acids by Aqueous Alteration on the Tagish Lake Meteorite Parent Body

    NASA Technical Reports Server (NTRS)

    Glavin, Daniel P.; Elsila, Jamie E.; Burton, Aaron S.; Callahan, Michael P.; Dworkin, Jason P.; Herd, Christopher D. K.

    2012-01-01

    The distribution and isotopic and enantiomeric compositions of amino acids found in three distinct fragments of the Tagish Lake C2-type carbonaceous chondrite were investigated via liquid chromatography fluorescence detection time-of-flight mass spectrometry and gas chromatography isotope ratio mass spectrometry. Large L-enantiomeric excesses (L(sub ee) approx. 43 to 59%) of the a-hydrogen aspartic and glutamic amino acids were measured in Tagish Lake, whereas alanine, another alpha-hydrogen protein amino acid, was found to be nearly racemic (D approx. L) using both techniques. Carbon isotope measurements of D- and L-aspartic acid and D- and L-alanine in Tagish Lake fall well outside of the terrestrial range and indicate that the measured aspartic acid enantioenrichment is indigenous to the meteorite. Alternate explanations for the Lexcesses of aspartic acid such as interference from other compounds present in the sample, analytical biases, or terrestrial amino acid contamination were investigated and rejected. These results can be explained by differences in the solid-solution phase behavior of aspartic acid, which can form conglomerate enantiopure solids during crystallization, and alanine, which can only form racemic crystals.

  7. Occurrence of Free d-Amino Acids and Aspartate Racemases in Hyperthermophilic Archaea

    PubMed Central

    Matsumoto, Megumi; Homma, Hiroshi; Long, Zhiqun; Imai, Kazuhiro; Iida, Toshii; Maruyama, Tadashi; Aikawa, Yuko; Endo, Isao; Yohda, Masafumi

    1999-01-01

    The occurrence of free d-amino acids and aspartate racemases in several hyperthermophilic archaea was investigated. Aspartic acid in all the hyperthermophilic archaea was highly racemized. The ratio of d-aspartic acid to total aspartic acid was in the range of 43.0 to 49.1%. The crude extracts of the hyperthermophiles exhibited aspartate racemase activity at 70°C, and aspartate racemase homologous genes in them were identified by PCR. d-Enantiomers of other amino acids (alanine, leucine, phenylalanine, and lysine) in Thermococcus strains were also detected. Some of them might be by-products of aspartate racemase. It is proven that d-amino acids are produced in some hyperthermophilic archaea, although their function is unknown. PMID:10515953

  8. Kinetic Trapping of Metastable Amino Acid Polymorphs

    PubMed Central

    2015-01-01

    Second harmonic generation (SHG) microscopy measurements indicate that inkjet-printed racemic solutions of amino acids can produce nanocrystals trapped in metastable polymorph forms upon rapid solvent evaporation. Polymorphism impacts the composition, distribution, and physico-kinetic properties of organic solids, with energetic arguments favoring the most stable polymorph. In this study, unfavored noncentrosymmetric crystal forms were observed by SHG microscopy. Polarization-dependent SHG measurement and synchrotron X-ray microdiffraction analysis of individual printed drops are consistent with formation of homochiral crystal production. Fundamentally, these results provide evidence supporting the ubiquity of Ostwald’s Rule of Stages, describing the hypothesized transitioning of crystals between metastable polymorphic forms in the early stages of crystal formation. Practically, the presence of homochiral metastable forms has implications on chiral resolution and on solid form preparations relying on rapid solvent evaporation. PMID:24451055

  9. Kinetic trapping of metastable amino acid polymorphs.

    PubMed

    Chowdhury, Azhad U; Dettmar, Christopher M; Sullivan, Shane Z; Zhang, Shijie; Jacobs, Kevin T; Kissick, David J; Maltais, Thora; Hedderich, Hartmut G; Bishop, Patricia A; Simpson, Garth J

    2014-02-12

    Second harmonic generation (SHG) microscopy measurements indicate that inkjet-printed racemic solutions of amino acids can produce nanocrystals trapped in metastable polymorph forms upon rapid solvent evaporation. Polymorphism impacts the composition, distribution, and physico-kinetic properties of organic solids, with energetic arguments favoring the most stable polymorph. In this study, unfavored noncentrosymmetric crystal forms were observed by SHG microscopy. Polarization-dependent SHG measurement and synchrotron X-ray microdiffraction analysis of individual printed drops are consistent with formation of homochiral crystal production. Fundamentally, these results provide evidence supporting the ubiquity of Ostwald's Rule of Stages, describing the hypothesized transitioning of crystals between metastable polymorphic forms in the early stages of crystal formation. Practically, the presence of homochiral metastable forms has implications on chiral resolution and on solid form preparations relying on rapid solvent evaporation. PMID:24451055

  10. Sublimation of natural amino acids and induction of asymmetry by meteoritic amino acids

    NASA Astrophysics Data System (ADS)

    Tarasevych, Arkadii V.; Guillemin, Jean-Claude

    It is believed that the homochirality of building blocks of life like amino acids (AAs) and sugars is a prerequisite requirement for the origin and evolution of life. Among different mechanisms that might have triggered the initial disparity in the enantiomeric ratio on the primitive Earth, the key roles were assigned to: (i) local chiral symmetry breaking and (ii) the inflow of extraterrestrial matter (eg the carbonaceous meteorites containing non-racemic AAs). Recently it has been revealed that sublimation, a subject almost completely neglected for a long time, gives a pathway to enantioenrichment of natural AAs (1,2 and references herein). Sublimation is however one of the key physical processes that occur on comets. Starting from a mixture with a low content of an enantiopure AA, a partial sublimation gives an important enrichment of the sublimate (1,2). The resulted disparity in the ratio between enantiomers of a partial sublimate is determined by the crystalline nature of the starting mixture: we observed a drastic difference in the behavior of (i) mixtures based on true racemic compounds and (ii) mechanical mixtures of two enantiopure solid phases. On the other hand, combination of crystallization and sublimation can lead to segregation of enantioenriched fractions starting from racemic composition of sublimable aliphatic AAs (Ala, Leu, Pro, Val) in mixtures with non-volatile enantiopure ones (Asn, Asp, Glu, Ser, Thr) (3). The resulted sense of chirality correlates with the handedness of the non-volatile AAs: the observed changes in enantiomeric ratios clearly demonstrate the preferential homochiral interactions and a tendency of natural amino acids to homochiral self-organization. It is noteworthy that just these 5 (Asn, Asp, Glu, Ser, Thr) out of 22 proteinogenic amino acids are able to local symmetry breaking. On the other hand, recent data on the enantiomeric composition of the Tagish Lake, a C2-type carbonaceous meteorite, revealed a large L

  11. Chirality of meteoritic free and IOM-derived monocarboxylic acids and implications for prebiotic organic synthesis

    NASA Astrophysics Data System (ADS)

    Aponte, José C.; Tarozo, Rafael; Alexandre, Marcelo R.; Alexander, Conel M. O.'D.; Charnley, Steven B.; Hallmann, Christian; Summons, Roger E.; Huang, Yongsong

    2014-04-01

    The origin of homochirality and its role in the development of life on Earth are among the most intriguing questions in science. It has been suggested that carbonaceous chondrites seeded primitive Earth with the initial organic compounds necessary for the origin of life. One of the strongest pieces of evidence supporting this theory is that certain amino acids in carbonaceous chondrites display a significant L-enantiomeric excess (ee), similar to those use by terrestrial life. Analyses of ee in meteoritic molecules other than amino acids would shed more light on the origins of homochirality. In this study we investigated the stereochemistry of two groups of compounds: (1) free monocarboxylic acids (MCAs) from CM2 meteorites LON 94101 and Murchison; and (2) the aliphatic side chains present in the insoluble organic matter (IOM) and extracted in the form of monocarboxylic acids (MCAs) from EET 87770 (CR2) and Orgueil (CI1). Contrary to the well-known ee observed for amino acids in meteorites, we found that meteoritic branched free and IOM-derived MCAs with 5-8 carbon atoms are essentially racemic. The racemic nature of these compounds is used to discuss the possible influence of ultraviolet circularly polarized light (UVCPL) and aqueous alterations on the parent body on chirality observed in in carbonaceous chondrites.

  12. Unusual Nonterrestrial L-proteinogenic Amino Acid excesses in the Tagish Lake Meteorite

    NASA Technical Reports Server (NTRS)

    Glavin, Daniel P.; Elsila, Jamie E.; Burton, Aaron S.; Callahan, Michael P.; Dworkin, Jason P.; Hilts, Robert W.; Herd, D. K.

    2012-01-01

    The distribution and isotopic and enantiomeric compositions of amino acids found in three distinct fragments of the Tagish Lake C2-type carbonaceous chondrite were investigated via liquid chromatography with fluorescence detection and time-of-flight mass spectrometry and gas chromatography isotope ratio mass spectrometry. Large L-enantiomeric excesses (L(sub ee) approximately 43-59%) of the alpha-hydrogen aspartic and glutamic amino acids were measured in Tagish Lake, whereas alanine, another alpha hydrogen protein amino acid, was found to be nearly racemic (D much approximately L) using both techniques. Carbon isotope measurements of D- and L-aspartic acid and 1)- and L-alanine in Tagish Lake fall well outside of the terrestrial range and indicate that the measured aspartic acid enantioenrichment is indigenous to the meteorite. Alternate explanations for the L-excesses of aspartic acid such as interference from other compounds present in the sample, analytical biases, or terrestrial amino acid contamination were investigated and rejected. These results can be explained by differences in the solid-solution phase behavior of aspartic acid, which can form conglomerate enantiopure solids during crystallization, and alanine, which can only form racemic crystals. Amplification of a small initial L-enantiomer excess during aqueous alteration on the meteorite parent body could have led to the large L-enrichments observed for aspartic acid and other conglomerate amino acids in Tagish Lake. The detection of non terrestrial L-proteinogenic amino acid excesses in the Tagish Lake meteorite provides support for the hypothesis that significant enantiomeric enrichments for some amino acids could form by abiotic processes prior to the emergence of life.

  13. A reexamination of amino acids in lunar soil

    NASA Technical Reports Server (NTRS)

    Brinton, K. L. F.; Bada, J. L.; Arnold, J. R.

    1993-01-01

    Amino acids in lunar soils provide an important indicator of the level of prebiotic organic compounds on the moon. The results provide insight into the chemistry of amino acid precursors, and furthermore, given the flux of carbonaceous material to the moon, we can evaluate the survival of organics upon impact. The amino acid contents of both hydrolyzed and unhydrolyzed hot-water extracts of Apollo 17 lunar soil were determined using ophthaldialdehyde/N-acetyl cysteine (OPA/NAC) derivatization followed by HPLC analysis. Previous studies of lunar amino acids were inconclusive, as the technique used (derivatization with ninhydrin followed by HPLC analysis) was unable to discriminate between cosmogenic amino acids and terrestrial contaminants. Cosmogenic amino acids are racemic, and many of the amino acids found in carbonaceous meteorites such as Murchison, i.e., alpha-amino-i-butyric acid (aib), are extremely rare on Earth. The ninhydrin method does not distinguish amino acid enantiomers, nor does it detect alpha-alkyl amino acids such as aib, whereas the OPA/NAC technique does both.

  14. A reexamination of amino acids in lunar soil

    NASA Astrophysics Data System (ADS)

    Brinton, K. L. F.; Bada, J. L.; Arnold, J. R.

    1993-03-01

    Amino acids in lunar soils provide an important indicator of the level of prebiotic organic compounds on the moon. The results provide insight into the chemistry of amino acid precursors, and furthermore, given the flux of carbonaceous material to the moon, we can evaluate the survival of organics upon impact. The amino acid contents of both hydrolyzed and unhydrolyzed hot-water extracts of Apollo 17 lunar soil were determined using ophthaldialdehyde/N-acetyl cysteine (OPA/NAC) derivatization followed by HPLC analysis. Previous studies of lunar amino acids were inconclusive, as the technique used (derivatization with ninhydrin followed by HPLC analysis) was unable to discriminate between cosmogenic amino acids and terrestrial contaminants. Cosmogenic amino acids are racemic, and many of the amino acids found in carbonaceous meteorites such as Murchison, i.e., alpha-amino-i-butyric acid (aib), are extremely rare on Earth. The ninhydrin method does not distinguish amino acid enantiomers, nor does it detect alpha-alkyl amino acids such as aib, whereas the OPA/NAC technique does both.

  15. Stable isotope and Ar/Ar evidence of prolonged multi-scale fluid flow during exhumation of orogenic crust: example from the Mont Blanc and Aar massifs (NW Alps)

    NASA Astrophysics Data System (ADS)

    Rolland, Yann; Rossi, Magali

    2015-04-01

    The spatial and temporal scales and the geometry of fluid pathways in a collisional orogen are investigated using stable isotope analysis (O, C, H) and 40Ar/39Ar dating of vein minerals formed at c. 11-16 Ma in the Mont Blanc and the Aar External Crystalline Massifs. In both massifs 40Ar/39Ar dating of veins adularia provides evidence for progressive crystallization from 16 to 9 Ma, and mainly at 11-12 Ma following veins opening during shear zone activity. The fluid flow duration thus ranges from 4 to 5 Ma in the two massifs. The δ18O values of vein quartz and calcite are similar to those of undeformed crystalline and sedimentary host-rocks, suggesting rock buffering, while carbon isotope ratios of vein calcites fall into three compositional groups. A-type veins have δ13C values that are buffered by the Helvetic metasediments, which suggests that these veins formed in a closed-system from a locally-derived CO2-rich fluid. The fluid in equilibrium with C-type veins has depleted δ13C values similar to mantle-CO2, while the intermediate δ13C values of B-type veins suggest mixing between the A-type and C-type fluids. These results are in agreement with crustal- to lithosphere-scale upward vertical fluid flow along vertical shear zones related to the strike-slip system bounding the Adriatic block since 16-20 Ma, connecting a deep-seated fluid to some downward flow in the sedimentary cover of External Crystalline Massifs.

  16. Development and validation of a predictive model for the influences of selected product and process variables on ascorbic acid degradation in simulated fruit juice.

    PubMed

    Gabriel, Alonzo A; Cayabyab, Jochelle Elysse C; Tan, Athalie Kaye L; Corook, Mark Lester F; Ables, Errol John O; Tiangson-Bayaga, Cecile Leah P

    2015-06-15

    A predictive response surface model for the influences of product (soluble solids and titratable acidity) and process (temperature and heating time) parameters on the degradation of ascorbic acid (AA) in heated simulated fruit juices (SFJs) was established. Physicochemical property ranges of freshly squeezed and processed juices, and a previously established decimal reduction times of Escherichiacoli O157:H7 at different heating temperatures were used in establishing a Central Composite Design of Experiment that determined the combinations of product and process variable used in the model building. Only the individual linear effects of temperature and heating time significantly (P<0.05) affected AA reduction (%AAr). Validating systems either over- or underestimated actual %AAr with bias factors 0.80-1.20. However, all validating systems still resulted in acceptable predictive efficacy, with accuracy factor 1.00-1.26. The model may be useful in establishing unique process schedules for specific products, for the simultaneous control and improvement of food safety and quality. PMID:25660889

  17. Formation of Meteoritic Amino Acids: Isovaline and its Isomers

    NASA Astrophysics Data System (ADS)

    Hudson, Reggie; Moore, Marla; Dworkin, Jason

    It has been known for several decades that amino acids, and other complex organics, are found in meteorites. In particular, Murchison (CM) samples contain over seventy amino acids, these being identified by high-level chromatographic methods. Among Murchison's amino acids, isovaline stands out as being both non-biological (non-protein) and having a relatively high abundance. While approximately equal amounts of D- and L- isovaline have been reported in Murchison and other CM meteorites, this molecule's structure appears to prohibit its racemization in aqueous solutions. We recently have investigated the low-temperature solid-phase chemistry of both isovaline and valine with an eye toward each molecule's formation, stability, and possible interconversions of their D and L enantiomers. Ion-irradiated isovalineand valine-containing ices were examined by IR spectroscopy and highly-sensitive liquid chromatography/time-of-flight mass spectral methods to assess both amino-acid destruction and racemization. Samples were studied in the presence and in the absence of water-ice, and the destruction of both isovaline and valine was measured as a function of radiation dose. In addition, we have synthesized isovaline, valine, and their amino acid isomers by solid-phase radiation-chemical pathways other than the oft-invoked Strecker process. This presentation will review and summarize some of our recent findings and place them in a context of related work. - Our work has been supported by a grant to the Goddard Center for Astrobiology through the NASA Astrobiology Institute. Experiments were performed in the Cosmic Ice Laboratory (RLH, MHM) and the Astrobiology Analytical Laboratory (JPD) at the NASA Goddard Space Flight Center.

  18. Amino acid geochemistry of fossil bones from the Rancho La Brea asphalt deposit, California

    USGS Publications Warehouse

    McMenamin, M.A.S.; Blunt, D.J.; Kvenvolden, K.A.; Miller, S.E.; Marcus, L.F.; Pardi, R.R.

    1982-01-01

    Low aspartic acid d:l ratios and modern collagenlike concentration values indicate that amino acids in bones from the Rancho La Brea asphalt deposit, Los Angeles, California are better preserved than amino acids in bones of equivalent age that have not been preserved in asphalt. Amino acids were recovered from 10 Rancho La Brea bone samples which range in age from less than 200 to greater than 36,000 yr. The calibrated rates of aspartic acid racemization range from 2.1 to 5.0 ?? 10-6yr-1. Although this wide range of rate constants decreases the level of confidence for age estimates, use of the larger rate constant of 5.0 ?? 10-6yr-1 provides minimum age estimates which fit the known stratigraphic and chronologic records of the Rancho La Brea deposits. ?? 1982.

  19. Isoaspartic acid is present at specific sites in myelin basic protein from multiple sclerosis patients: could this represent a trigger for disease onset?

    PubMed

    Friedrich, Michael G; Hancock, Sarah E; Raftery, Mark J; Truscott, Roger J W

    2016-01-01

    Multiple sclerosis (MS) is associated with breakdown of the myelin sheath that coats neurons in the central nervous system. The cause of MS is not known, although the pathogenesis involves destruction of myelin by the immune system. It was the aim of this study to examine the abundant myelin protein, myelin basic protein (MBP), to determine if there are sites of modification that may be characteristic for MS. MBP from the cerebellum was examined from controls and MS patients across the age range using mass spectrometry and amino acid analysis. Amino acid racemization data indicated that myelin basic protein is long-lived and proteomic analysis of MBP showed it to be highly modified. A common modification of MBP was racemization of Asp and this was significantly greater in MS patients. In long-lived proteins, L-Asp and L-Asn can racemize to three other isomers, D-isoAsp, L-isoAsp and D-Asp and this is significant because isoAsp formation in peptides renders them immunogenic.Proteomic analysis revealed widespread modifications of MBP with two surface regions that are altered in MS. In particular, isoAsp was significantly elevated at these sites in MS patients. The generation of isoAsp could be responsible for eliciting an immune response to modified MBP and therefore be implicated in the etiology of MS. PMID:27519525

  20. Abscisic Acid Structure-Activity Relationships in Barley Aleurone Layers and Protoplasts (Biological Activity of Optically Active, Oxygenated Abscisic Acid Analogs).

    PubMed

    Hill, R. D.; Liu, J. H.; Durnin, D.; Lamb, N.; Shaw, A.; Abrams, S. R.

    1995-06-01

    Optically active forms of abscisic acid (ABA) and their oxygenated metabolites were tested for their biological activity by examining the effects of the compounds on the reversal of gibberellic acid-induced [alpha]-amylase activity in barley (Hordeum vulgare cv Himalaya) aleurone layers and the induction of gene expression in barley aleurone protoplasts transformed with a chimeric construct containing the promoter region of an albumin storage protein gene. Promotion of the albumin storage protein gene response had a more strict stereochemical requirement for elicitation of an ABA response than inhibition of [alpha]-amylase gene expression. The naturally occurring stereoisomer of ABA and its metabolites were more effective at eliciting an ABA-like response. ABA showed the highest activity, followed by 7[prime]-hydroxyABA, with phaseic acid being the least active. Racemic 8[prime]-hydroxy-2[prime],3[prime]-dihydroABA, an analog of 8[prime]-hydroxyABA, was inactive, whereas racemic 2[prime],3[prime]-dihydroABA was as effective as ABA. The differences in response of the same tissue to the ABA enantiomers lead us to conclude that there exists more than one type of ABA receptor and/or multiple signal transduction pathways in barley aleurone tissue. PMID:12228494

  1. Abscisic Acid Structure-Activity Relationships in Barley Aleurone Layers and Protoplasts (Biological Activity of Optically Active, Oxygenated Abscisic Acid Analogs).

    PubMed Central

    Hill, R. D.; Liu, J. H.; Durnin, D.; Lamb, N.; Shaw, A.; Abrams, S. R.

    1995-01-01

    Optically active forms of abscisic acid (ABA) and their oxygenated metabolites were tested for their biological activity by examining the effects of the compounds on the reversal of gibberellic acid-induced [alpha]-amylase activity in barley (Hordeum vulgare cv Himalaya) aleurone layers and the induction of gene expression in barley aleurone protoplasts transformed with a chimeric construct containing the promoter region of an albumin storage protein gene. Promotion of the albumin storage protein gene response had a more strict stereochemical requirement for elicitation of an ABA response than inhibition of [alpha]-amylase gene expression. The naturally occurring stereoisomer of ABA and its metabolites were more effective at eliciting an ABA-like response. ABA showed the highest activity, followed by 7[prime]-hydroxyABA, with phaseic acid being the least active. Racemic 8[prime]-hydroxy-2[prime],3[prime]-dihydroABA, an analog of 8[prime]-hydroxyABA, was inactive, whereas racemic 2[prime],3[prime]-dihydroABA was as effective as ABA. The differences in response of the same tissue to the ABA enantiomers lead us to conclude that there exists more than one type of ABA receptor and/or multiple signal transduction pathways in barley aleurone tissue. PMID:12228494

  2. Recyclable Ligands for the Non-Enzymatic Dynamic Kinetic Resolution of Challenging α-Amino Acids.

    PubMed

    Nian, Yong; Wang, Jiang; Zhou, Shengbin; Wang, Shuni; Moriwaki, Hiroki; Kawashima, Aki; Soloshonok, Vadim A; Liu, Hong

    2015-10-26

    Structurally simple and inexpensive chiral tridentate ligands were employed for substantially advancing the purely chemical dynamic kinetic resolution (DKR) of unprotected racemic tailor-made α-amino acids (TM-α-AAs), enabling the first DKR of TM-α-AAs bearing tertiary alkyl chains as well as multiple unprotected functional groups. Owing to the operationally convenient conditions, virtually complete stereoselectivity, and full recyclability of the source of chirality, this method should find wide applications for the preparation of TM-α-AAs, especially on large scale. PMID:26367134

  3. Extraterrestrial Amino Acids in the Almahata Sitta Meteorite

    NASA Technical Reports Server (NTRS)

    Glavin, Daniel P.; Aubrey, Andrew D.; Callahan, Michael P.; Dworkin, Jason P.; Elsila, Jamie E.; Parker, Eric T.; Bada, Jeffrey L.

    2010-01-01

    Amino acid analysis of a meteorite fragment of asteroid 2008 TC3 called Almahata Sitta was carried out using reverse-phase liquid chromatography coupled with UV fluorescence detection and time-of-flight mass spectrometry (LC-FD/ToF-MS) as part of a sample analysis consortium. LC-FD/ToF-MS analyses of hot-water extracts from the meteorite revealed a complex distribution of two- to seven-carbon aliphatic amino acids and one- to three-carbon amines with abundances ranging from 0.5 to 149 parts-per-billion (ppb). The enantiomeric ratios of the amino acids alanine, R-amino-n-butyric acid (beta-ABA), 2-amino-2-methylbutanoic acid (isovaline), and 2-aminopentanoic acid (norvaline) in the meteorite were racemic (D/L approximately 1), indicating that these amino acids are indigenous to the meteorite and not terrestrial contaminants. Several other non-protein amino acids were also identified in the meteorite above background levels including alpha-aminoisobutyric acid (alpha-AIB), 4-amino-2- methylbutanoic acid, 4-amino-3-methylbutanoic acid, and 3-, 4-, and 5-aminopentanoic acid. The total abundances of isovaline and alpha-AIB in Almahata Sitta are 1000 times lower than the abundances of these amino acids found in the CM carbonaceous chondrite Murchison. The extremely low abundances and unusual distribution of five carbon amino acids in Almahata Sitta compared to Cl, CM, and CR carbonaceous chondrites may reflect extensive thermal alteration of amino acids on the parent asteroid by partial melting during formation or subsequent impact shock heating. It is also possible that amino acids were synthesized by catalytic reactions on the parent body after asteroid 2008 TC3 cooled to lower temperatures.

  4. Extraterrestrial amino acids in the Almahata Sitta meteorite

    NASA Astrophysics Data System (ADS)

    Glavin, Daniel P.; Aubrey, Andrew D.; Callahan, Michael P.; Dworkin, Jason P.; Elsila, Jamie E.; Parker, Eric T.; Bada, Jeffrey L.; Jenniskens, Peter; Shaddad, Muawia H.

    2010-10-01

    Amino acid analysis of a meteorite fragment of asteroid 2008 TC3 called Almahata Sitta was carried out using reverse-phase liquid chromatography coupled with UV fluorescence detection and time-of-flight mass spectrometry (LC-FD/ToF-MS) as part of a sample analysis consortium. LC-FD/ToF-MS analyses of hot-water extracts from the meteorite revealed a complex distribution of two- to seven-carbon aliphatic amino acids and one- to three-carbon amines with abundances ranging from 0.5 to 149 parts-per-billion (ppb). The enantiomeric ratios of the amino acids alanine, β-amino-n-butyric acid, 2-amino-2-methylbutanoic acid (isovaline), and 2-aminopentanoic acid (norvaline) in the meteorite were racemic (D/L ˜ 1), indicating that these amino acids are indigenous to the meteorite and not terrestrial contaminants. Several other nonprotein amino acids were also identified in the meteorite above background levels including α-aminoisobutyric acid (α-AIB), 4-amino-2-methylbutanoic acid, 4-amino-3-methylbutanoic acid, and 3-, 4-, and 5-aminopentanoic acid. The total abundances of isovaline and α-AIB in Almahata Sitta are approximately 1000 times lower than the abundances of these amino acids found in the CM carbonaceous chondrite Murchison. The extremely low abundances and unusual distribution of five-carbon amino acids in Almahata Sitta compared to CI, CM, and CR carbonaceous chondrites may reflect extensive thermal alteration of amino acids on the parent asteroid by partial melting during formation or subsequent impact shock heating. It is also possible that amino acids were synthesized by catalytic reactions on the parent body after asteroid 2008 TC3 cooled to lower temperatures, or introduced as a contaminant from unrelated meteorite clasts and chemically altered by α-decarboxylation.

  5. Metabolic annotation of 2-ethylhydracrylic acid.

    PubMed

    Ryan, Robert O

    2015-08-25

    Increased levels of the organic acid, 2-ethylhydracrylic acid (2-EHA) occur in urine of subjects with impaired L(+)-isoleucine metabolism. Chiral intermediates formed during isoleucine degradation are (S) enantiomers. Blockage of (S) pathway flux drives racemization of (2S, 3S) L(+)-isoleucine and its (2S, 3R) stereoisomer, L(+)-alloisoleucine. This non-protein amino acid is metabolized to (R)-2-methylbutyryl CoA via enzymes common to branched chain amino acid degradation. Subsequently, (R) intermediates serve as alternate substrates for three valine metabolic enzymes, generating 2-EHA. Once formed, 2-EHA accumulates because it is poorly recognized by distal valine pathway enzymes. Thus, urinary 2-EHA represents a biomarker of isoleucine pathway defects. 2-EHA levels are also increased in rats exposed to the industrial solvent, ethylene glycol monomethyl ether or the neurotoxin precursor, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In these cases, a block in (S) pathway isoleucine catabolism occurs at the level of (S)-2-methylbutyryl CoA conversion to tiglyl CoA via inhibition of electron transferring flavoprotein/ubiquinone oxidoreductase dependent reactions. Elevated urinary 2-EHA in propionyl CoA carboxylase deficiency and methylmalonic aciduria results from a buildup of distal intermediates in the (S) pathway of isoleucine degradation. In Barth syndrome and dilated cardiomyopathy with ataxia syndrome, 2-EHA is a byproduct of impeded propionyl CoA entry into the Krebs cycle. PMID:26115894

  6. Prionic Acid: An Effective Sex Attractant for an Important Pest of Sugarcane, Dorysthenes granulosus (Coleoptera: Cerambycidae: Prioninae).

    PubMed

    Wickham, Jacob D; Lu, Wen; Jin, Tao; Peng, Zhengqiang; Guo, Dongfeng; Millar, Jocelyn G; Hanks, Lawrence M; Chen, Yi

    2016-02-01

    Male Dorysthenes granulosus (Thomson, 1860) (Coleoptera: Cerambycidae: Prioninae) were caught in traps baited with racemic 3,5-dimethyldodecanoic acid (prionic acid) during field screening trials in China that tested known cerambycid pheromones. This species is an important pest of sugarcane (Saccharum officinarum L.). In follow-up dose-response trials, plastic sachets loaded with 1 or 0.1 mg of prionic acid were equally attractive to male beetles, whereas lower doses were no better than controls. Two commercial prionic acid lures also were attractive, suggesting that traps baited with prionic acid can be rapidly incorporated into integrated pest management programs targeting this major pest. It is likely that this compound is a major component of the female-produced sex pheromone of D. granulosus because this species is in the same subfamily as Prionus californicus Motschulsky, 1845, the species from which prionic acid was originally identified. PMID:26362990

  7. Meteoritic Amino Acids: Diversity in Compositions Reflects Parent Body Histories.

    PubMed

    Elsila, Jamie E; Aponte, José C; Blackmond, Donna G; Burton, Aaron S; Dworkin, Jason P; Glavin, Daniel P

    2016-06-22

    The analysis of amino acids in meteorites dates back over 50 years; however, it is only in recent years that research has expanded beyond investigations of a narrow set of meteorite groups (exemplified by the Murchison meteorite) into meteorites of other types and classes. These new studies have shown a wide diversity in the abundance and distribution of amino acids across carbonaceous chondrite groups, highlighting the role of parent body processes and composition in the creation, preservation, or alteration of amino acids. Although most chiral amino acids are racemic in meteorites, the enantiomeric distribution of some amino acids, particularly of the nonprotein amino acid isovaline, has also been shown to vary both within certain meteorites and across carbonaceous meteorite groups. Large l-enantiomeric excesses of some extraterrestrial protein amino acids (up to ∼60%) have also been observed in rare cases and point to nonbiological enantiomeric enrichment processes prior to the emergence of life. In this Outlook, we review these recent meteoritic analyses, focusing on variations in abundance, structural distributions, and enantiomeric distributions of amino acids and discussing possible explanations for these observations and the potential for future work. PMID:27413780

  8. Meteoritic Amino Acids: Diversity in Compositions Reflects Parent Body Histories

    PubMed Central

    2016-01-01

    The analysis of amino acids in meteorites dates back over 50 years; however, it is only in recent years that research has expanded beyond investigations of a narrow set of meteorite groups (exemplified by the Murchison meteorite) into meteorites of other types and classes. These new studies have shown a wide diversity in the abundance and distribution of amino acids across carbonaceous chondrite groups, highlighting the role of parent body processes and composition in the creation, preservation, or alteration of amino acids. Although most chiral amino acids are racemic in meteorites, the enantiomeric distribution of some amino acids, particularly of the nonprotein amino acid isovaline, has also been shown to vary both within certain meteorites and across carbonaceous meteorite groups. Large l-enantiomeric excesses of some extraterrestrial protein amino acids (up to ∼60%) have also been observed in rare cases and point to nonbiological enantiomeric enrichment processes prior to the emergence of life. In this Outlook, we review these recent meteoritic analyses, focusing on variations in abundance, structural distributions, and enantiomeric distributions of amino acids and discussing possible explanations for these observations and the potential for future work. PMID:27413780

  9. Extraterrestrial Amino Acids in the Almahata Sitta Meteorite

    NASA Technical Reports Server (NTRS)

    Glavin, Daniel P.; Aubrey, Andrew D.; Callahan, Michael P.; Dworkin, Jason P.; Elsila, Jamie E.; Parker, Eric T.; Bada, Jeffrey L.

    2009-01-01

    Amino acid analysis of a meteorite fragment of asteroid 2008 TC(sub 3) called Almahata Sitta was carried out using reverse-phase high-perfo rmance liquid chromatography coupled with UV fluorescence detection a nd time-of-flight mass spectrometry (HPLC-FD/ToF-MS) as part of a sam ple analysis consortium. HPLC analyses of hot-water extracts from the meteorite revealed a complex distribution of two- to six-carbon aliph atic amino acids and one- to three carbon amines with abundances rang ing from 0.5 to 149 parts-per-billion (ppb). The enantiomeric ratios of the amino acids alanine, Beta-amino-n-butyric acid (Beta-ABA), 2-amino-2- methylbutanoic acid (isovaline), and 2-aminopentanoic acid (no rvaline) in the meteorite were racemic (D/L approximately 1), indicat ing that these amino acids are indigenous to the meteorite and not te rrestrial contaminants. Several other non-protein amino acids were also identified in the meteorite above background levels including alpha -aminoisobutyric acid (alpha-AIB), 4-amino-2- methybutanoic acid, 4-a mino-3-methylbutanoic acid, and 3-, 4-, and 5-aminopentanoic acid. Th e total abundances of isovaline and AlB in Almahata Sitta are approximately 1000 times lower than the abundances of these amino acids found in the CM carbonaceous meteorite Murchison. The extremely love abund ances and unusual distribution of five carbon amino acids in Almahata Sitta compared to Cl, CM, and CR carbonaceous meteorites and may be due to extensive thermal alteration of amino acids on the parent aster oid by partial melting during formation or impact shock heating.

  10. Solid-Phase Formation Of Isovaline, A Non-Biological, Meteoritic Amino Acid

    NASA Astrophysics Data System (ADS)

    Hudson, Reggie L.; Lewis, A. S.; Moore, M. H.; Dworkin, J. P.; Glavin, D. P.

    2007-10-01

    Among the Murchison (CM) meteoritic amino acids, isovaline stands out as being non-biological (nonprotein) and having a high abundance. Approximately equal amounts of D- and L-isovaline have been reported in CM meteorites, but the molecule's structure appears to prohibit racemization in aqueous solutions. While it is possible that isovaline could be made by the oft-studied Strecker reaction, laboratory experiments have seldom been able to produce this molecule from realistic molecular precursors. Recently we have investigated the low-temperature solid-phase chemistry of isovaline with an eye toward the molecule's formation, its stability, and the interconversion of its D- and L-enantiomers. Ion-irradiated isovaline-containing ices were examined by IR spectroscopy and highly-sensitive LC/ToF-MS methods to assess both amino acid destruction and racemization. Samples were studied both in the presence and absence of water-ice, and the destruction of isovaline was measured as a function of radiation dose. In addition, we have continued our earlier work on solid-phase amino acid formation, extending it to cover isovaline. In this presentation we will report the results of these newer investigations. This work was supported by a grant to the Goddard Center for Astrobiology through the NASA Astrobiology Institute. AL was supported by an award from the Summer Undergraduate Internship in Astrobiology program.

  11. New 4-hydroxy-N-(2-hydroxyethyl)butanamides: Structure and acidity

    NASA Astrophysics Data System (ADS)

    Duarte-Hernández, Angélica M.; Contreras, Rosalinda; Suárez-Moreno, Galdina V.; González, Felipe J.; Flores-Parra, Angelina

    2015-02-01

    Optically active new 4-hydroxy-N-(2-hydroxyethyl)butanamides are reported. The structure in the solid state of four racemic mixtures and three enantiomeric pure compounds was determined by X-ray diffraction. The solid state arrangements of enantiomerically pure compounds were compared with those of their racemic mixtures. The butanamides prefer lineal conformations in the solid state. They form dimers and polymers through intermolecular hydrogen bonds. Variable temperature 1H NMR experiments were performed in order to analyse the strength of the hydrogen bonds in the neutral molecules in solution. The pKa values of the dihydroxybutanamides in DMSO determined by cyclic voltammetric (11.1-14.5) were lower than those reported for amides RNHCOR without hydroxyl groups (25.9). The latter motivated us to investigate the role of hydrogen bonds in the stabilization of the corresponding anions and in consequence in the acidity of the amides. The explanation of the enhanced Nsbnd H acidity of dihydroxybutanamides was found in the cyclic voltammetric experiments, in conductimetric titrations using nBu4NOH in methanol and titration with CsOH in acetonitrile. The optimised structures for the neutral molecules and their mono and dianions calculated by ab-initio HF(6-31 + G∗) and B3LYP(6-31 + G∗) methods supported the explanation of the enhanced Nsbnd H acidity.

  12. Binding of [alpha, alpha]-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design

    SciTech Connect

    Ilies, Monica; Di Costanzo, Luigi; Dowling, Daniel P.; Thorn, Katherine J.; Christianson, David W.

    2011-10-21

    Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of {alpha},{alpha}-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase I and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional {alpha}-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase.

  13. Radioiodinated methyl-branched fatty acids: Evaluation of catabolites formed in vivo

    SciTech Connect

    Knapp, F.F. Jr.; Reske, S.N.; Kirsch, G.; Ambrose, K.R.; Blystone, S.L.; Goodman, M.M.

    1987-01-01

    Radioiodinated terminal iodophenyl-substituted long-chain fatty acids containing either racemic mono-methyl or geminal dimethyl-branching in the alkyl chain have been shown to exhibit delayed myocardial clearance properties which make these agents useful for the SPECT evaluation of myocardial fatty acid uptake patterns. Although the myocardial clearance rate of 15-(p-iodophenyl)-3-R,S- methylpentadecanoic acid (BMIPP) is considerably delayed, in comparison with the IPPA straight-chain analogue, analysis of the radioiodinated lipids present in the outflow tract of isolated rat hearts administered BMIPP have clearly demonstrated the presence of a polar metabolite. The synthesis of ..beta..-hydroxy fatty acids has been developed to allow investigation of the possible formation of ..beta..-hydroxy catabolites in vivo. The preparation of ..beta..-hydroxy BMIPP and ..beta..-hydroxy IPPA are described, and the possible significance of their formation in vivo discussed. 4 figs.

  14. Selective adsorption of L- and D-amino acids on calcite: Implications for biochemical homochirality

    NASA Technical Reports Server (NTRS)

    Hazen, R. M.; Filley, T. R.; Goodfriend, G. A.

    2001-01-01

    The emergence of biochemical homochirality was a key step in the origin of life, yet prebiotic mechanisms for chiral separation are not well constrained. Here we demonstrate a geochemically plausible scenario for chiral separation of amino acids by adsorption on mineral surfaces. Crystals of the common rock-forming mineral calcite (CaCO(3)), when immersed in a racemic aspartic acid solution, display significant adsorption and chiral selectivity of d- and l-enantiomers on pairs of mirror-related crystal-growth surfaces. This selective adsorption is greater on crystals with terraced surface textures, which indicates that d- and l-aspartic acid concentrate along step-like linear growth features. Thus, selective adsorption of linear arrays of d- and l-amino acids on calcite, with subsequent condensation polymerization, represents a plausible geochemical mechanism for the production of homochiral polypeptides on the prebiotic Earth.

  15. Analysis of Chiral Carboxylic Acids in Meteorites

    NASA Technical Reports Server (NTRS)

    Burton, A. S.; Elsila, J. E.; Hein, J. E.; Aponte, J. C.; Parker, E. T.; Glavin, D. P.; Dworkin, J. P.

    2015-01-01

    Homochirality of amino acids in proteins and sugars in DNA and RNA is a critical feature of life on Earth. In the absence of a chiral driving force, however, reactions leading to the synthesis of amino acids and sugars result in racemic mixtures. It is currently unknown whether homochirality was necessary for the origins of life or if it was a product of early life. The observation of enantiomeric excesses of certain amino acids of extraterrestrial origins in meteorites provides evidence to support the hypothesis that there was a mechanism for the preferential synthesis or destruction of a particular amino acid enantiomer [e.g., 1-3]. The cause of the observed chiral excesses is un-clear, although at least in the case of the amino acid isovaline, the degree of aqueous alteration that occurred on the meteorite parent body is correlated to the isovaline L-enantiomeric excess [3, 4]. This suggests that chiral symmetry is broken and/or amplified within the meteorite parent bodies. Besides amino acids, there have been only a few reports of other meteoritic compounds found in enantiomeric excess: sugars and sugar acids [5, 6] and the hydroxy acid lactic acid [7]. Determining whether or not additional types of molecules in meteorites are also present in enantiomeric excesses of extraterrestrial information will provide insights into mechanisms for breaking chiral symmetry. Though the previous measurements (e.g., enantiomeric composition of lactic acid [7], and chiral carboxylic acids [8]) were made by gas chromatography-mass spectrometry, the potential for increased sensitivity of liquid chromatography-mass spectrometry (LC-MS) analyses is important because for many meteorite samples, only small sample masses are available for study. Furthermore, at least in the case of amino acids, many of the largest amino acid enantiomeric excesses were observed in samples that contained lower abundances (tens of ppb) of a given amino acid enantiomer. In the present work, we describe

  16. Development of HPLC Chiral Stationary Phases Based on (+)-(18-Crown-6)-2,3,11,12-tetracarboxylic Acid and Their Applications.

    PubMed

    Hyun, Myung Ho

    2015-09-01

    Crown ether-based chiral stationary phases (CSPs) have been known to be useful for the resolution of racemic primary amino compounds. In particular, CSPs based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid have been reported to be useful for the resolution of secondary amino compounds as well as primary amino compounds. In this article, the process of developing various CSPs based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid to improve the chiral recognition efficiency and/or the stability of the CSPs and their applications to the resolution of various primary and nonprimary amino compounds are reviewed. PMID:26237013

  17. Lewis acid catalysed methylation of N-(9H-fluoren-9-yl)methanesulfonyl (Fms) protected lipophilic α-amino acid methyl esters.

    PubMed

    Leggio, Antonella; Alò, Danila; Belsito, Emilia Lucia; Di Gioia, Maria Luisa; Romio, Emanuela; Siciliano, Carlo; Liguori, Angelo

    2015-08-01

    This work reports an efficient Lewis acid catalysed N-methylation procedure of lipophilic α-amino acid methyl esters in solution phase. The developed methodology involves the use of the reagent system AlCl3/diazomethane as methylating agent and α-amino acid methyl esters protected on the amino function with the (9H-fluoren-9-yl)methanesulfonyl (Fms) group. The removal of Fms protecting group is achieved under the same conditions to those used for Fmoc removal. Thus the Fms group can be interchangeable with the Fmoc group in the synthesis of N-methylated peptides using standard Fmoc-based strategies. Finally, the absence of racemization during the methylation reaction and the removal of Fms group were demonstrated by synthesising a pair of diastereomeric dipeptides. PMID:25921656

  18. The fate of amino acids during simulated meteoritic impact.

    PubMed

    Bertrand, Marylène; van der Gaast, Sjerry; Vilas, Faith; Hörz, Friedrich; Haynes, Gerald; Chabin, Annie; Brack, Andre; Westall, Frances

    2009-12-01

    Delivery of prebiotic molecules, such as amino acids and peptides, in meteoritic/micrometeoritic materials to early Earth during the first 500 million years is considered to be one of the main processes by which the building blocks of life arrived on Earth. In this context, we present a study in which the effects of impact shock on amino acids and a peptide in artificial meteorites composed of saponite clay were investigated. The samples were subjected to pressures ranging from 12-28.9 GPa, which simulated impact velocities of 2.4-5.8 km/s for typical silicate-silicate impacts on Earth. Volatilization was determined by weight loss measurement, and the amino acid and peptide response was analyzed by gas chromatography-mass spectrometry. For all compounds, degradation increased with peak pressure. At the highest shock pressures, amino acids with an alkyl side chain were more resistant than those with functional side chains. The peptide cleaved into its two primary amino acids. Some chiral amino acids experienced partial racemization during the course of the experiment. Our data indicate that impact shock may act as a selective filter to the delivery of extraterrestrial amino acids via carbonaceous chondrites. PMID:20041747

  19. Behavioral Responses of Plum Curculio (Coleoptera: Curculionidae) to Different Enantiomer Concentrations and Blends of the Synthetic Aggregation Pheromone Grandisoic Acid.

    PubMed

    Hock, Virginia; Chouinard, Gérald; Lucas, Éric; Cormier, Daniel; Leskey, Tracy C; Wright, Starker E; Zhang, Aijun; Pichette, André

    2015-04-01

    The plum curculio, Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), is an important pest of fruit in North America. Males produce an aggregation pheromone (grandisoic acid) that attracts both sexes of the northern univoltine and the southern multivoltine strains. Grandisoic acid ((1R,2S)-1-methyl-2-(1-methylethenyl)-cyclobutaneacetic acid) is a chiral molecule containing one chiral center. A synthetic racemic mixture will contain two optical isomers that are mirror images of each other with equal amounts of (+)- and (-)-enantiomeric isomers. Male plum curculio only produce the (+) enantiomer. Some enantiomers can have antagonistic effects on the attraction of weevils to pheromones. An understanding of the effect of both enantiomers on the behaviour of plum curculio is needed to develop more efficient trap baits. Behavioural bioassays were conducted in a dual-choice still-air vertical olfactometer using a quantity of 1.5 ml of both (+) and (-) synthetic enantiomers and the racemic mixture of grandisoic acid with live female responders to determine which concentration and enantiomeric purity is the most attractive and if there is an antagonistic effect of the unnatural (-) enantiomer. Results indicated that plum curculio were attracted to low concentrations of the (+) enantiomer at 72% enantiomeric excess, but that strains were attracted to different concentrations of the (+) enantiomer (2×10(-7) mg/ml for univoltine, 2×10(-9) mg/ml for multivoltine). PMID:26470165

  20. A continuous multi-millennial record of surficial bivalve mollusk shells from the São Paulo Bight, Brazilian shelf

    NASA Astrophysics Data System (ADS)

    Dexter, Troy A.; Kaufman, Darrell S.; Krause, Richard A.; Barbour Wood, Susan L.; Simões, Marcello G.; Huntley, John Warren; Yanes, Yurena; Romanek, Christopher S.; Kowalewski, Michał

    2014-03-01

    To evaluate the potential of using surficial shell accumulations for paleoenvironmental studies, an extensive time series of individually dated specimens of the marine infaunal bivalve mollusk Semele casali was assembled using amino acid racemization (AAR) ratios (n = 270) calibrated against radiocarbon ages (n = 32). The shells were collected from surface sediments at multiple sites across a sediment-starved shelf in the shallow sub-tropical São Paulo Bight (São Paulo State, Brazil). The resulting 14C-calibrated AAR time series, one of the largest AAR datasets compiled to date, ranges from modern to 10,307 cal yr BP, is right skewed, and represents a remarkably complete time series: the completeness of the Holocene record is 66% at 250-yr binning resolution and 81% at 500-yr binning resolution. Extensive time-averaging is observed for all sites across the sampled bathymetric range indicating long water depth-invariant survival of carbonate shells at the sediment surface with low net sedimentation rates. Benthic organisms collected from active depositional surfaces can provide multi-millennial time series of biomineral records and serve as a source of geochemical proxy data for reconstructing environmental and climatic trends throughout the Holocene at centennial resolution. Surface sediments can contain time-rich shell accumulations that record the entire Holocene, not just the present.

  1. Dynamic Kinetic Resolution Approach for the Asymmetric Synthesis of Tetrahydrobenzodiazepines Using Transfer Hydrogenation by Chiral Phosphoric Acid.

    PubMed

    Horiguchi, Kosaku; Yamamoto, Eri; Saito, Kodai; Yamanaka, Masahiro; Akiyama, Takahiko

    2016-06-01

    Asymmetric synthesis of tetrahydrobenzodiazepines was achieved by transfer hydrogenation of dihydrobenzodiazepines with benzothiazoline having a hydrogen-bonding donor substituent by means of a newly synthesized chiral phosphoric acid. This method was applicable to various racemic dihydrobenzodiazepines to give the corresponding products in good yields with excellent diastereoselectivities and enantioselectivities taking advantage of the dynamic kinetic resolution. Furthermore, the effect of bulky substituent at 3,3'-position on the catalyst and hydrogen-bonding donor substituent on benzothiazoline was fully elucidated by the theoretical study. PMID:27150449

  2. Enantioselective hydrogenation of pyruvic acid oxime to alanine on Pd/Alumina

    SciTech Connect

    Borszeky, K.; Mallat, T.; Aeschiman, R.

    1996-06-01

    The chemo- and enantioselective hydrogenation of pyruvic acid oxime have been studied on Pd/alumina, the latter in the presence of the 1,2-amino alcohol type alkaloids ephedrine, cinchonidine, and cinchonine. High yields of racemic alanine (90-98%) were obtained in the absence of alkaloids in polar solvents at 0-45{degrees}C and 10 bar. Enantioselection increased with higher temperature and alkalid: oxime molar ratio. A 1:1 ephedrine: oxime molar ratio afforded the best enantiomeric excess (26%). The presence of alkaloid resulted in a decrease of reaction rate by a factor of up to 140, compared to the racemic hydrogenation. Based on X-ray crystal structure analysis of the alkaloid-pyruvic acid oxime adduct, a mechanism is proposed for the steric course of the reaction. Extended interactions by multiple H bonds between the adsorbed alkaloid-oxime salt units on the Pd surface is assumed to be at the origin of the moderate enantioselectivity and the very low enantioselective hydrogenation rate. 28 refs., 5 figs., 3 tabs.

  3. Extraterrestrial Amino Acids in Ureilites Including Almahata Sitta

    NASA Technical Reports Server (NTRS)

    Burton, A. S.; Glavin, D. P.; Callahan, M. P.; Dworkin, J. P.

    2011-01-01

    Ureilites are a class of meteorites that lack chondrules (achondrites) but have relatively high carbon abundances, averaging approx.3 wt %. Using highly sensitive liquid chromatography coupled with UV fluorescence and time-of-flight mass spectrometry (LC-FD/ToF-MS), it was recently determined that there are amino acids in. fragment 94 of the Almahata Sitta ureilite[l]. Based on the presence of amino acids that are rare in the Earth's biosphere, as well as the near-racemic enantiomeric ratios of marry of the more common amino acids, it was concluded that most of the detected amino acids were indigenous to the meteorite. Although the composition of the Almahata Sitta ureilite appears to be unlike other recovered ureilites, the discovery of amino acids in this meteorite raises the question of whether other ureilites rnav also contain amino acids. Herein we present the results of LC-FDlTo.F-MS analyses of: a sand sample from the Almahata Sitta strewn held, Almahata Sitta fragments 425 (an ordinary H5 chondrite) and 427 (ureilite), as well as an Antarctic ureilite (Allan lulls, ALHA 77257).

  4. Chiral Recognition Studies of α-(Nonafluoro-tert-butoxy)carboxylic Acids by NMR Spectroscopy.

    PubMed

    Nemes, Anikó; Csóka, Tamás; Béni, Szabolcs; Farkas, Viktor; Rábai, József; Szabó, Dénes

    2015-06-19

    Three chiral α-(nonafluoro-tert-butoxy)carboxylic acids (R)-1, (RS)-2, (R)-3 were synthesized to examine their application as chiral solvating agents with amines. As a model compound, first (S)- and/or (RS)-α-phenylethylamine was used, and their diastereomeric salts were investigated by (1)H and (19)F NMR and ECD spectroscopy. The NMR spectroscopic studies were carried out at room temperature using the slightly polar CDCl3 and apolar C6D6 as solvents in 5 mM and 54 mM concentrations. The difference of the chemical shifts (Δδ) in the diastereomeric complexes is comparable with other, well-known chiral derivatizing and solvating agents (e.g., Mosher's acid, Pirkle's alcohol). Diastereomeric salts of racemic acids (RS)-1 and (RS)-2 with biologically active amines (1R,2S)-ephedrine and (S)-dapoxetine were also investigated by (19)F NMR spectroscopy. PMID:26024423

  5. Deracemization of Amino Acids by Partial Sublimation and via Homochiral Self-Organization

    NASA Astrophysics Data System (ADS)

    Tarasevych, Arkadii V.; Sorochinsky, Alexander E.; Kukhar, Valery P.; Guillemin, Jean-Claude

    2013-04-01

    Deracemization of a 50/50 mixture of enantiomers of aliphatic amino acids (Ala, Leu, Pro, Val) can be achieved by a simple sublimation of a pre-solubilized solid mixture of the racemates with a huge amount of a less-volatile optically active amino acid (Asn, Asp, Glu, Ser, Thr). The choice of chirality correlates with the handedness of the enantiopure amino acids—Asn, Asp, Glu, Ser, and Thr. The deracemization, enantioenrichment and enantiodepletion observed in these experiments clearly demonstrate the preferential homochiral interactions and a tendency of natural amino acids to homochiral self-organization. These data may contribute toward an ultimate understanding of the pathways by which prebiological homochirality might have emerged.

  6. Amino-acid racemizarion in Quaternary shell deposits at Willapa Bay, Washington

    USGS Publications Warehouse

    Kvenvolden, K.A.; Blunt, D.J.; Clifton, H.E.

    1979-01-01

    Extents of racemization ( d l ratios) of amino acids in fossil Saxidomus giganteus (Deshayes) and Ostrea lurida Carpenter were measured on shell deposits exposed at 21 sites on the east side of Willapa Bay, Washington. Amino acids from Saxidomus show less variability in d Spl ratios and, therefore, are of greater use in correlation and age estimation than are amino acids from Ostrea. Shells of two different ages, about 120,000 ?? 40,000 yr old and about 190,000 ?? 40,000 yr old, are present. These ages correspond to Stages 5 and 7 of the marine isotope record defined by Shackleton and Opdyke in 1973 and hence the shell deposits likely formed during two different high stands of sea level. The stratigraphic record at Willapa Bay is consistent with this interpretation. ?? 1979.

  7. Enantioselective kinetic resolution of phenylalkyl carboxylic acids using metagenome‐derived esterases

    PubMed Central

    Fernández‐Álvaro, Elena; Kourist, Robert; Winter, Julia; Böttcher, Dominique; Liebeton, Klaus; Naumer, Christian; Eck, Jürgen; Leggewie, Christian; Jaeger, Karl‐Erich; Streit, Wolfgang; Bornscheuer, Uwe T.

    2010-01-01

    Summary Enantiomerically pure β‐arylalkyl carboxylic acids are important synthetic intermediates for the preparation of a wide range of compounds with biological and pharmacological activities. A library of 83 enzymes isolated from the metagenome was searched for activity in the hydrolysis of ethyl esters of three racemic phenylalkyl carboxylic acids by a microtiter plate‐based screening using a pH‐indicator assay. Out of these, 20 enzymes were found to be active and were subjected to analytical scale biocatalysis in order to determine their enantioselectivity. The most enantioselective and also enantiocomplementary biocatalysts were then used for preparative scale reactions. Thus, both enantiomers of each of the three phenylalkyl carboxylic acids studied could be obtained in excellent optical purity and high yields. PMID:21255306

  8. Reasons for the occurrence of the twenty coded protein amino acids

    NASA Technical Reports Server (NTRS)

    Weber, A. L.; Miller, S. L.

    1981-01-01

    Factors involved in the selection of the 20 protein L-alpha-amino acids during chemical evolution and the early stages of Darwinian evolution are discussed. The selection is considered on the basis of the availability in the primitive ocean, function in proteins, the stability of the amino acid and its peptides, stability to racemization, and stability on the transfer RNA. It is concluded that aspartic acid, glutamic acid, arginine, lysine, serine and possibly threonine are the best choices for acidic, basic and hydroxy amino acids. The hydrophobic amino acids are reasonable choices, except for the puzzling absences of alpha-amino-n-butyric acid, norvaline and norleucine. The choices of the sulfur and aromatic amino acids seem reasonable, but are not compelling. Asparagine and glutamine are apparently not primitive. If life were to arise on another planet, it would be expected that the catalysts would be poly-alpha-amino acids and that about 75% of the amino acids would be the same as on the earth.

  9. Reconstruction of peak water levels, peak discharges and long-term occurrence of extreme- as well as smaller pre-instrumental flood events of river Aare, Limmat, Reuss, Rhine and Saane in Switzerland. Part I

    NASA Astrophysics Data System (ADS)

    Wetter, Oliver; Tuttenuj, Daniel

    2016-04-01

    systematically analysed the period from 1446-1542 and could prove a large number of pre-instrumental flood events of river Rhine, Birs, Birsig and Wiese in Basel. All in all the weekly led account books contained 54 Rhine flood events, whereas chroniclers and annalists only recorded seven floods during the same period. This is a ratio of almost eight to one. This large difference points to the significantly sharper "observation skills" of the account books towards smaller floods, which may be explained by the fact that bridges can be endangered by relatively small floods because of driftwood, whereas it is known that chroniclers or annalists were predominantly focussing on spectacular (extreme) flood events. We [Oliver Wetter and Daniel Tuttenuj] are now able to present first preliminary results of reconstructed peak water levels and peak discharges of pre instrumental river Aare-, Emme-, Limmat-, Reuss-, Rhine- and Saane floods. These first results clearly show the strengths as well as the limits of the data and method used, depending mainly on the river types. Of the above mentioned rivers only the floods of river Emme could not be reconstructed whereas the long-term development of peak water levels and peak discharges of the other rivers clearly correlate with major local and supra-regional Swiss flood corrections over time. PhD student Daniel Tuttenuj is going to present the results for river Emme and Saane (see Abstract Daniel Tuttenuj), whereas Dr Oliver Wetter is going to present the results for the other rivers and gives a first insight on long-term recurring periods of smaller river Birs-, Birsig-, Rhine- and Wiese flood events based on the analysis of the weekly led account books "Wochenausgabenbücher der Stadt Basel" (see also Abstract of Daniel Tuttenuj).

  10. Reconstruction of peak water levels, peak discharges and long-term occurrence of extreme- as well as smaller pre-instrumental flood events of river Aare, Limmat, Reuss, Rhine and Saane in Switzerland. Part II.

    NASA Astrophysics Data System (ADS)

    Tuttenuj, Daniel; Wetter, Oliver

    2016-04-01

    contained 54 Rhine flood events, whereas chroniclers and annalists only recorded seven floods during the same period. This is a ratio of almost eight to one. This large difference points to the significantly sharper "observation skills" of the account books towards smaller floods, which may be explained by the fact that bridges can be endangered by relatively small floods because of driftwood, whereas it is known that chroniclers or annalists were predominantly focussing on spectacular (extreme) flood events. We [Oliver Wetter and Daniel Tuttenuj] are now able to present first preliminary results of reconstructed peak water levels and peak discharges of pre instrumental river Aare-, Emme-, Limmat-, Reuss-, Rhine- and Saane floods. These first results clearly show the strengths as well as the limits of the data and method used, depending mainly on the river types. Of the above mentioned rivers only the floods of river Emme could not be reconstructed whereas the long-term development of peak water levels and peak discharges of the other rivers clearly correlate with major local and supra-regional Swiss flood corrections over time. PhD student Daniel Tuttenuj is going to present the results of river Emme and Saane, whereas Dr Oliver Wetter is going to present the results for the other rivers and gives a first insight on long-term recurring periods of smaller river Birs, Birsig, Rhine and Wiese flood events based on the analysis of the weekly led account books "Wochenausgabenbücher der Stadt Basel" (see Abstract Oliver Wetter).

  11. Intermolecular Vibrations of Hydrophobic Amino Acids

    NASA Astrophysics Data System (ADS)

    Williams, Michael Roy Casselman

    Hydrophobic amino acids interact with their chemical environment through a combination of electrostatic, hydrogen bonding, dipole, induced dipole, and dispersion forces. These interactions all have their own characteristic energy scale and distance dependence. The low-frequency (0.1-5 THz, 5-150 cm-1) vibrational modes of amino acids in the solid state are a direct indicator of the interactions between the molecules, which include interactions between an amino acid functional group and its surroundings. This information is central to understanding the dynamics and morphology of proteins. The alpha-carbon is a chiral center for all of the hydrophobic amino acids, meaning that they exist in two forms, traditionally referred to as L- and D-enantiomers. This nomenclature indicates which direction the molecule rotates plane-polarized visible light (levorotory and dextrorotory). Chiral a-amino acids in proteins are exclusively the L-variety In the solid state, the crystal lattice of the pure L-enantiomer is the mirror image of the D-enantiomer crystal lattice. These solids are energetically identical. Enantiomers also have identical spectroscopic properties except when the measurement is polarization sensitive. A mixture of equal amounts D- and L-amino acid enantiomers can crystallize into a racemic (DL-) structure that is different from that of the pure enantiomers. Whether a solution of both enantiomers will crystallize into a racemic form or spontaneously resolve into a mixture of separate D- and L-crystals largely depends on the interactions between molecules available in the various possible configurations. This is an active area of research. Low-frequency vibrations with intermolecular character are very sensitive to changes in lattice geometry, and consequently the vibrational spectra of racemic crystals are usually quite distinct from the spectra of the crystals of the corresponding pure enantiomers in the far-infrared (far-IR). THz time-domain spectroscopy (THz

  12. Nonproteinogenic D-amino acids at millimolar concentrations are a toxin for anaerobic microorganisms relevant to early Earth and other anoxic planets.

    PubMed

    Nixon, Sophie L; Cockell, Charles S

    2015-03-01

    The delivery of extraterrestrial organics to early Earth provided a potentially important source of carbon and energy for microbial life. Optically active organic compounds of extraterrestrial origin exist in racemic form, yet life on Earth has almost exclusively selected for L- over D-enantiomers of amino acids. Although D-enantiomers of proteinogenic amino acids are known to inhibit aerobic microorganisms, the role of concentrated nonproteinogenic meteoritic D-amino acids on anaerobic metabolisms relevant to early Earth and other anoxic planets such as Mars is unknown. Here, we test the inhibitory effect of D-enantiomers of two nonproteinogenic amino acids common to carbonaceous chondrites, norvaline and α-aminobutyric acid, on microbial iron reduction. Three pure strains (Geobacter bemidjiensis, Geobacter metallireducens, Geopsychrobacter electrodiphilus) and an iron-reducing enrichment culture were grown in the presence of 10 mM D-enantiomers of both amino acids. Further tests were conducted to assess the inhibitory effect of these D-amino acids at 1 and 0.1 mM. The presence of 10 mM D-norvaline and D-α-aminobutyric acid inhibited microbial iron reduction by all pure strains and the enrichment. G. bemidjiensis was not inhibited by either amino acid at 0.1 mM, but D-α-aminobutyric acid still inhibited at 1 mM. Calculations using published meteorite accumulation rates to the martian surface indicate D-α-aminobutyric acid may have reached inhibitory concentrations in little over 1000 years during peak infall. These data show that, on a young anoxic planet, the use of one enantiomer over another may render the nonbiological enantiomer an environmental toxin. Processes that generate racemic amino acids in the environment, such as meteoritic infall or impact synthesis, would have been toxic processes and could have been a selection pressure for the evolution of early racemases. PMID:25695622

  13. Binding of α,α-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design1

    PubMed Central

    Ilies, Monica; Di Costanzo, Luigi; Dowling, Daniel P.; Thorn, Katherine J.; Christianson, David W.

    2011-01-01

    Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design, and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of α,α-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2- methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase I and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional α-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase. PMID:21728378

  14. Amino acids

    MedlinePlus

    Amino acids are organic compounds that combine to form proteins . Amino acids and proteins are the building blocks of life. When proteins are digested or broken down, amino acids are left. The human body uses amino acids ...

  15. The origin of amino acids in lunar regolith samples

    NASA Astrophysics Data System (ADS)

    Elsila, Jamie E.; Callahan, Michael P.; Dworkin, Jason P.; Glavin, Daniel P.; McLain, Hannah L.; Noble, Sarah K.; Gibson, Everett K.

    2016-01-01

    We analyzed the amino acid content of seven lunar regolith samples returned by the Apollo 16 and Apollo 17 missions and stored under NASA curation since collection using ultrahigh-performance liquid chromatography with fluorescence detection and time-of-flight mass spectrometry. Consistent with results from initial analyses shortly after collection in the 1970s, we observed amino acids at low concentrations in all of the curated samples, ranging from 0.2 parts-per-billion (ppb) to 42.7 ppb in hot-water extracts and 14.5-651.1 ppb in 6 M HCl acid-vapor-hydrolyzed, hot-water extracts. Amino acids identified in the Apollo soil extracts include glycine, D- and L-alanine, D- and L-aspartic acid, D- and L-glutamic acid, D- and L-serine, L-threonine, and L-valine, all of which had previously been detected in lunar samples, as well as several compounds not previously identified in lunar regoliths: α-aminoisobutyric acid (AIB), D- and L-β-amino-n-butyric acid (β-ABA), DL-α-amino-n-butyric acid, γ-amino-n-butyric acid, β-alanine, and ε-amino-n-caproic acid. We observed an excess of the L enantiomer in most of the detected proteinogenic amino acids, but racemic alanine and racemic β-ABA were present in some samples. We also examined seven samples from Apollo 15, 16, and 17 that had been previously allocated to a non-curation laboratory, as well as two samples of terrestrial dunite from studies of lunar module engine exhaust that had been stored in the same laboratory. The amino acid content of these samples suggested that contamination had occurred during non-curatorial storage. We measured the compound-specific carbon isotopic ratios of glycine, β-alanine, and L-alanine in Apollo regolith sample 70011 and found values of -21‰ to -33‰. These values are consistent with those seen in terrestrial biology and, together with the enantiomeric compositions of the proteinogenic amino acids, suggest that terrestrial biological contamination is a primary source of the

  16. Chiral analysis of amino acids using electrochemical composite bienzyme biosensors.

    PubMed

    Domínguez, R; Serra, B; Reviejo, A J; Pingarrón, J M

    2001-11-15

    The construction and performance of bienzyme amperometric composite biosensors for the selective determination of l- or d-amino acids is reported. D- or L-Amino acid oxidase, horseradish peroxidase, and the mediator ferrocene were coimmobilized by simple physical inclusion into the bulk of a graphite-70% Teflon electrode matrix. Working conditions including amino acid oxidase loading and pH were optimized. Studies on the repeatability of the amperometric response obtained at +0.00 V, with and without regeneration of the electrode surface by polishing, on the useful lifetime of one single biosensor and on the reproducibility in the fabrication of different biosensors illustrate the robustness of the bioelectrodes design. Calibration plots by both amperometry in stirred solutions and flow injection with amperometric detection were obtained for L-arginine, L-phenylalanine, L-leucine, L-methionine, L-tryptophan, D-leucine, D-methionine, D-serine, and D-valine. Differences in sensitivity were discussed in terms of the hydrophobicity of the substrate and of the electrode surface. The bienzyme composite electrode was applied to the determination of L- and D-amino acids in racemic samples, as well as to the estimation of the L-amino acids content in muscatel grapes. PMID:11700983

  17. Identification, purification, and characterization of a novel amino acid racemase, isoleucine 2-epimerase, from Lactobacillus species.

    PubMed

    Mutaguchi, Yuta; Ohmori, Taketo; Wakamatsu, Taisuke; Doi, Katsumi; Ohshima, Toshihisa

    2013-11-01

    Accumulation of d-leucine, d-allo-isoleucine, and d-valine was observed in the growth medium of a lactic acid bacterium, Lactobacillus otakiensis JCM 15040, and the racemase responsible was purified from the cells and identified. The N-terminal amino acid sequence of the purified enzyme was GKLDKASKLI, which is consistent with that of a putative γ-aminobutyrate aminotransferase from Lactobacillus buchneri. The putative γ-aminobutyrate aminotransferase gene from L. buchneri JCM 1115 was expressed in recombinant Escherichia coli and then purified to homogeneity. The enzyme catalyzed the racemization of a broad spectrum of nonpolar amino acids. In particular, it catalyzed at high rates the epimerization of l-isoleucine to d-allo-isoleucine and d-allo-isoleucine to l-isoleucine. In contrast, the enzyme showed no γ-aminobutyrate aminotransferase activity. The relative molecular masses of the subunit and native enzyme were estimated to be about 49 kDa and 200 kDa, respectively, indicating that the enzyme was composed of four subunits of equal molecular masses. The Km and Vmax values of the enzyme for l-isoleucine were 5.00 mM and 153 μmol·min(-1)·mg(-1), respectively, and those for d-allo-isoleucine were 13.2 mM and 286 μmol·min(-1)·mg(-1), respectively. Hydroxylamine and other inhibitors of pyridoxal 5'-phosphate-dependent enzymes completely blocked the enzyme activity, indicating the enzyme requires pyridoxal 5'-phosphate as a coenzyme. This is the first evidence of an amino acid racemase that specifically catalyzes racemization of nonpolar amino acids at the C-2 position. PMID:24039265

  18. Identification, Purification, and Characterization of a Novel Amino Acid Racemase, Isoleucine 2-Epimerase, from Lactobacillus Species

    PubMed Central

    Mutaguchi, Yuta; Ohmori, Taketo; Wakamatsu, Taisuke; Doi, Katsumi

    2013-01-01

    Accumulation of d-leucine, d-allo-isoleucine, and d-valine was observed in the growth medium of a lactic acid bacterium, Lactobacillus otakiensis JCM 15040, and the racemase responsible was purified from the cells and identified. The N-terminal amino acid sequence of the purified enzyme was GKLDKASKLI, which is consistent with that of a putative γ-aminobutyrate aminotransferase from Lactobacillus buchneri. The putative γ-aminobutyrate aminotransferase gene from L. buchneri JCM 1115 was expressed in recombinant Escherichia coli and then purified to homogeneity. The enzyme catalyzed the racemization of a broad spectrum of nonpolar amino acids. In particular, it catalyzed at high rates the epimerization of l-isoleucine to d-allo-isoleucine and d-allo-isoleucine to l-isoleucine. In contrast, the enzyme showed no γ-aminobutyrate aminotransferase activity. The relative molecular masses of the subunit and native enzyme were estimated to be about 49 kDa and 200 kDa, respectively, indicating that the enzyme was composed of four subunits of equal molecular masses. The Km and Vmax values of the enzyme for l-isoleucine were 5.00 mM and 153 μmol·min−1·mg−1, respectively, and those for d-allo-isoleucine were 13.2 mM and 286 μmol·min−1·mg−1, respectively. Hydroxylamine and other inhibitors of pyridoxal 5′-phosphate-dependent enzymes completely blocked the enzyme activity, indicating the enzyme requires pyridoxal 5′-phosphate as a coenzyme. This is the first evidence of an amino acid racemase that specifically catalyzes racemization of nonpolar amino acids at the C-2 position. PMID:24039265

  19. Study of the Binding Energies between Unnatural Amino Acids and Engineered Orthogonal Tyrosyl-tRNA Synthetases

    PubMed Central

    Ren, Wei; Truong, Tan M.; Ai, Hui-wang

    2015-01-01

    We utilized several computational approaches to evaluate the binding energies of tyrosine (Tyr) and several unnatural Tyr analogs, to several orthogonal aaRSes derived from Methanocaldococcus jannaschii and Escherichia coli tyrosyl-tRNA synthetases. The present study reveals the following: (1) AutoDock Vina and ROSETTA were able to distinguish binding energy differences for individual pairs of favorable and unfavorable aaRS-amino acid complexes, but were unable to cluster together all experimentally verified favorable complexes from unfavorable aaRS-Tyr complexes; (2) MD-MM/PBSA provided the best prediction accuracy in terms of clustering favorable and unfavorable enzyme-substrate complexes, but also required the highest computational cost; and (3) MM/PBSA based on single energy-minimized structures has a significantly lower computational cost compared to MD-MM/PBSA, but still produced sufficiently accurate predictions to cluster aaRS-amino acid interactions. Although amino acid-aaRS binding is just the first step in a complex series of processes to acylate a tRNA with its corresponding amino acid, the difference in binding energy, as shown by MD-MM/PBSA, is important for a mutant orthogonal aaRS to distinguish between a favorable unnatural amino acid (unAA) substrate from unfavorable natural amino acid substrates. Our computational study should assist further designing and engineering of orthogonal aaRSes for the genetic encoding of novel unAAs. PMID:26220470

  20. Study of the Binding Energies between Unnatural Amino Acids and Engineered Orthogonal Tyrosyl-tRNA Synthetases

    NASA Astrophysics Data System (ADS)

    Ren, Wei; Truong, Tan M.; Ai, Hui-Wang

    2015-07-01

    We utilized several computational approaches to evaluate the binding energies of tyrosine (Tyr) and several unnatural Tyr analogs, to several orthogonal aaRSes derived from Methanocaldococcus jannaschii and Escherichia coli tyrosyl-tRNA synthetases. The present study reveals the following: (1) AutoDock Vina and ROSETTA were able to distinguish binding energy differences for individual pairs of favorable and unfavorable aaRS-amino acid complexes, but were unable to cluster together all experimentally verified favorable complexes from unfavorable aaRS-Tyr complexes; (2) MD-MM/PBSA provided the best prediction accuracy in terms of clustering favorable and unfavorable enzyme-substrate complexes, but also required the highest computational cost; and (3) MM/PBSA based on single energy-minimized structures has a significantly lower computational cost compared to MD-MM/PBSA, but still produced sufficiently accurate predictions to cluster aaRS-amino acid interactions. Although amino acid-aaRS binding is just the first step in a complex series of processes to acylate a tRNA with its corresponding amino acid, the difference in binding energy, as shown by MD-MM/PBSA, is important for a mutant orthogonal aaRS to distinguish between a favorable unnatural amino acid (unAA) substrate from unfavorable natural amino acid substrates. Our computational study should assist further designing and engineering of orthogonal aaRSes for the genetic encoding of novel unAAs.

  1. Application and comparison of high-speed countercurrent chromatography and high performance liquid chromatography in preparative enantioseparation of α-substitution mandelic acids

    PubMed Central

    Tong, Shengqiang; Zhang, Hu; Shen, Mangmang; Ito, Yoichiro; Yan, Jizhong

    2014-01-01

    Preparative enantioseparations of α-cyclopentylmandelic acid and α-methylmandelic acid by high-speed countercurrent chromatography (HSCCC) and high performance liquid chromatography (HPLC) were compared using hydroxypropy-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD) as the chiral mobile phase additives. In preparative HPLC the enantioseparation was achieved on the ODS C18 reverse phase column with the mobile phase composed of a mixture of acetonitrile and 0.10 mol L−1 phosphate buffer at pH 2.68 containing 20 mmol L−1 HP-β-CD for α-cyclopentylmandelic acid and 20 mmol L−1 SBE-β-CD for α-methylmandelic acid. The maximum sample size for α-cyclopentylmandelic acid and α-methylmandelic acid was only about 10 mg and 5 mg, respectively. In preparative HSCCC the enantioseparations of these two racemates were performed with the two-phase solvent system composed of n-hexane-methyl tert.-butyl ether-0.1 molL−1 phosphate buffer solution at pH 2.67 containing 0.1 mol L−1 HP-β-CD for α-cyclopentylmandelic acid (8.5:1.5:10, v/v/v) and 0.1 mol L−1 SBE-β-CD for α-methylmandelic acid (3:7:10, v/v/v). Under the optimum separation conditions, total 250 mg of racemic α-cyclopentylmandelic acid could be completely enantioseparated by HSCCC with HP-β-CD as a chiral mobile phase additive in a single run, yielding 105-110 mg of enantiomers with 95-98% purity and 85-90% recovery. But, no complete enantioseparation of α-methylmandelic acid was achieved by preparative HSCCC with either of the chiral selectors due to their limited enantioselectivity. In this paper preparative enantioseparation by HSCCC and HPLC was compared from various aspects. PMID:25983356

  2. Preferential polymerization and adsorption of L-optical isomers of amino acids relative to D-optical isomers on kaolinite templates.

    NASA Technical Reports Server (NTRS)

    Jackson, T. A.

    1971-01-01

    Experiments on the polymerization of the L- and D-optical isomers of aspartic acid and serine using kaolinite as a catalyst showed that the L-optical isomers were polymerized at a much higher rate than the D-optical isomers; racemic (DL-) mixtures were polymerized at an intermediate rate. The peptides formed from the L-monomers were preferentially adsorbed by the clay. In the absence of kaolinite, no significant or consistent difference in the behavior of the L- and D-optical isomers was observed. In experiments on the adsorption of L- and D-phenylalanine by kaolinite, the L-optical isomer was preferentially adsorbed.

  3. Involvement of abscisic acid in correlative control of flower abscission in soybean

    SciTech Connect

    Yarrow, G.L.

    1985-01-01

    Studies were carried out in three parts: (1) analysis of endogenous abscisic acid (ABA) in abscising and non-abscising flowers, (2) partitioning of radio-labelled ABA and photoassimilates within the soybean raceme, and (3) shading experiments, wherein endogenous levels, metabolism and partitioning of ABA were determined. Endogenous concentrations of ABA failed to show any consistent relationship to abscission of soybean flowers. Partitioning of radiolabelled ABA and photoassimilates displayed consistently higher sink strengths (% DPM) for both /sup 3/H-ABA and /sup 14/C-photoassimilates for non-abscising flowers than for abscising flowers within control racemes. Shading flowers with aluminum foil, 48 hrs prior to sampling, resulted in lowered endogenous ABA concentrations at 12, 17 and 22 days after anthesis (DAA), but not at 0 or 4 DAA. No differences were found in the catabolism of /sup 3/H-ABA between shaded (abscising) and non-shaded (non-abscising) flowers. Reduced partitioning of ABA and photoassimilates to shaded flowers resulted when shades were applied at 0, 4, 12, and 17 DAA, but not at 22 DAA.

  4. Dry heat popping of amaranth seed might damage some of its essential amino acids.

    PubMed

    Tovar, L R; Brito, E; Takahashi, T; Miyazawa, T; Soriano, J; Fujimoto, K

    1989-12-01

    Amaranth was a major crop among the Aztecs. In Mexico the seed is popped and eaten with brown sugar. The crude protein content of the seed is 14 +/- 2% but its contents of lysine and tryptophan are 6.2 and 1.6 g/16 g N respectively. We developed a popping method based on a fluid bed system (FBS) whereas the traditional method (TM) is just to pop the seeds manually in a hot plate. Assays carried out were evaluation of racemization of the amaranth protein due to heat treatment, amino acid composition of the raw and heat treated seeds and a biological experiment testing whether leucine was the most limiting amino acid of amaranth protein. Male rats were fed both popped amaranths and roasted amaranth. Parboiled amaranth and casein were controls. The results were: (a) Lys, Arg and Cys were damaged in the heat treated seeds; (b) Asp, Met, Glu, Ala and Phe were racemized in that decreasing order in the seeds popped and roasted by the TM; (c) the estimated net protein retention (NPR) and estimated net protein utilization (NPU) of popped amaranths by either method were not different, but were lower than for the parboiled amaranth. The parboiled amaranth was not different from casein; (d) Leu was not the most limiting amino acid in any of the amaranth seeds tested. After Lys, sulfur amino acids appear to be the next most limiting in severely heat treated amaranth. The FBS seems to be a promising method for popping amaranth at industrial level. PMID:2631086

  5. Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: A pilot study

    PubMed Central

    Keith, Dove J.; Butler, Judy A.; Bemer, Brett; Dixon, Brian; Johnson, Shawn; Garrard, Mary; Sudakin, Daniel L.; Christensen, J. Mark; Pereira, Cliff; Hagen, Tory M.

    2014-01-01

    Lipoic acid (LA) shows promise as a beneficial micronutrient toward improving elder health. Studies using old rats show that (R)-α-LA (R-LA) significantly increases low molecular weight antioxidants that otherwise decline with age. Despite this rationale for benefiting human health, little is known about age-associated alterations in absorption characteristics of LA, or whether the commercially available racemic mixture of LA (R,S-LA) is equally as bioavailable as the naturally occurring R-enantiomer. To address these discrepancies, a pilot study was performed to establish which form of LA is most effectively absorbed in older subjects relative to young volunteers. Young adults (average age = 32 years) and older adults (average age = 79 years) each received 500 mg of either R- or R,S-LA. Blood samples were collected for 3 h after supplementation. After a washout period they were given the other chiral form of LA not originally ingested. Results showed that 2 out of 6 elder males exhibited greater maximal plasma LA and area under the curve for the R-form of LA versus the racemic mixture. The elder subjects also demonstrated a reduced time to reach maximal plasma LA concentration following R-LA supplementation than for the racemic mixture. In contrast, young males had a tendency for increased bioavailability of R,S-LA. Overall, bioavailability for either LA isoform was much more variable between older subjects compared to young adults. Plasma glutathione levels were not altered during the sampling period. Thus subject age, and potential for varied response, should be considered when determining an LA supplementation regimen. PMID:22609537

  6. Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study.

    PubMed

    Keith, Dove J; Butler, Judy A; Bemer, Brett; Dixon, Brian; Johnson, Shawn; Garrard, Mary; Sudakin, Daniel L; Christensen, J Mark; Pereira, Cliff; Hagen, Tory M

    2012-09-01

    Lipoic acid (LA) shows promise as a beneficial micronutrient toward improving elder health. Studies using old rats show that (R)-α-LA (R-LA) significantly increases low molecular weight antioxidants that otherwise decline with age. Despite this rationale for benefiting human health, little is known about age-associated alterations in absorption characteristics of LA, or whether the commercially available racemic mixture of LA (R,S-LA) is equally as bioavailable as the naturally occurring R-enantiomer. To address these discrepancies, a pilot study was performed to establish which form of LA is most effectively absorbed in older subjects relative to young volunteers. Young adults (average age=32 years) and older adults (average age=79 years) each received 500 mg of either R- or R,S-LA. Blood samples were collected for 3h after supplementation. After a washout period they were given the other chiral form of LA not originally ingested. Results showed that 2 out of 6 elder males exhibited greater maximal plasma LA and area under the curve for the R-form of LA versus the racemic mixture. The elder subjects also demonstrated a reduced time to reach maximal plasma LA concentration following R-LA supplementation than for the racemic mixture. In contrast, young males had a tendency for increased bioavailability of R,S-LA. Overall, bioavailability for either LA isoform was much more variable between older subjects compared to young adults. Plasma glutathione levels were not altered during the sampling period. Thus subject age, and potential for varied response, should be considered when determining an LA supplementation regimen. PMID:22609537

  7. Folic Acid

    MedlinePlus

    Folic acid is a B vitamin. It helps the body make healthy new cells. Everyone needs folic acid. For women who may get pregnant, it is really important. Getting enough folic acid before and during pregnancy can prevent major birth ...

  8. Folic Acid

    MedlinePlus

    Folic acid is used to treat or prevent folic acid deficiency. It is a B-complex vitamin needed by ... Folic acid comes in tablets. It usually is taken once a day. Follow the directions on your prescription label ...

  9. Aspartic acid

    MedlinePlus

    ... also called asparaginic acid. Aspartic acid helps every cell in the body work. It plays a role in: Hormone production and release Normal nervous system function Plant sources of aspartic acid include: Legumes such as ...

  10. Determination of the D and L isomers of some protein amino acids present in soils

    NASA Technical Reports Server (NTRS)

    Pollock, G. E.; Cheng, C.-N.; Cronin, S. E.

    1977-01-01

    The D and L isomers of some protein amino acids present in soils were measured by using a gas chromatographic technique. The results of two processing procedures were compared to determine the better method. Results of the comparison indicated that the determination of D and L percentages requires amino acid purification if one is to obtain accurate data. It was found that very significant amounts of D-alanine, D-aspartic acid, and D-glutamic acid were present in the contemporary soils studied. Valine, isoleucine, leucine, proline, and phenylalanine generally contained only a trace to very small amounts of the D isomer. It is probable that the D-amino acids from the alanine, aspartic, and glutamic acids are contributed to the soil primarily via microorganisms. The finding of very significant quantities of some D-amino acids (about 5-16%) in present-day soils may alert some investigators of geological sediments to a possible problem in using amino acid racemization as an age-dating technique.

  11. Optimisation of a system for the co-translational incorporation of a keto amino acid and its application to a tumour-specific Anticalin.

    PubMed

    Reichert, Andreas J; Poxleitner, Gabriele; Dauner, Martin; Skerra, Arne

    2015-12-01

    The bioorthogonal keto group has attracted interest for the site-specific chemical conjugation of recombinant proteins under mild conditions, e.g. with aminooxy-functionalised fluorescent probes, radiometal chelates, toxins or polymers. However, the cotranslational incorporation of the corresponding non-canonical amino acid p-acetyl-L-phenylalanine (Apa) into proteins expressed in Escherichia coli by means of amber suppression using a previously described system with a mutated tRNA and an engineered tyrosyl-tRNA synthetase from Methanococcus jannaschii shows limited efficiency and considerable promiscuity towards endogenous amino acids. Employing a one-plasmid system that encodes all three components required for selection, i.e. the modified aminoacyl-tRNA synthetase (aaRS), the cognate amber suppressor tRNA and the enhanced green fluorescent protein equipped with an amber stop codon and serving as reporter, we have generated an Apa-specific aaRS&tRNA pair with considerably improved efficiency (17-fold increased expression) and also fidelity (6-fold). To this end, both the aaRS and the tRNA were subjected to doped random mutagenesis and selection in altogether four evolutionary cycles using fluorescence-activated bacterial cell sorting as well as automated screening of microcultures. The resulting aaRS&tRNA pair was applied to the functionalisation of an Anticalin with specificity towards oncofetal fibronectin by introducing a keto group at a permissible site for subsequent conjugation with a fluorescent dye, thus allowing visualisation of this tumour target under the microscope. PMID:26405058

  12. Acid Rain.

    ERIC Educational Resources Information Center

    Openshaw, Peter

    1987-01-01

    Provides some background information on acid deposition. Includes a historical perspective, describes some effects of acid precipitation, and discusses acid rain in the United Kingdom. Contains several experiments that deal with the effects of acid rain on water quality and soil. (TW)

  13. Amino acids and hydrocarbons approximately 3,800-Myr old in the Isua rocks, southwestern Greenland

    NASA Technical Reports Server (NTRS)

    Nagy, B.; Engel, M. H.; Zumberge, J. E.; Ogino, H.; Chang, S. Y.

    1981-01-01

    Results of an analysis of amino acids and hydrocarbons found in the Isua banded iron formation, which contains the oldest known rocks on earth, are discussed. Similarities are pointed out between the relative amino acid abundances of the Isua rocks and those of lichens found on their surfaces, and a lack of substantial racemization indicated by the low D/L ratios in the 3800-million year old rock samples is noted. Experimental results showing the possibility of amino acid diffusion from lichens into the rocks are presented. Comparisons of the Isua rock amino acid D/L ratios with those reported for samples from other regions indicates that none of the Isua amino acids are older than a few tens of thousands to a few hundred thousand years. Analyses of the saturated hydrocarbons of the Isua samples reveals no odd carbon number preference, which may indicate antiquity, however laboratory experiments have shown that amino acids and aromatic and saturated aliphatic hydrocarbons could not have survived the metamorphic history of the Isua rocks. The evidence presented thus suggests that the amino acids and hydrocarbons found are not of the age of the sediments.

  14. Neuroprotective Activity of Thioctic Acid in Central Nervous System Lesions Consequent to Peripheral Nerve Injury

    PubMed Central

    Ghelardini, Carla; Nwankwo, Innocent E.; Pacini, Alessandra

    2013-01-01

    Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (−)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/−)-, (+)-, or (−)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/−)- or (−)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies. PMID:24527432

  15. Lactide Synthesis and Chirality Control for Polylactic acid Production.

    PubMed

    Van Wouwe, Pieter; Dusselier, Michiel; Vanleeuw, Evelien; Sels, Bert

    2016-05-10

    Polylactic acid (PLA) is a very promising biodegradable, renewable, and biocompatible polymer. Aside from its production, its application field is also increasing, with use not only in commodity applications but also as durables and in biomedicine. In the current PLA production scheme, the most expensive part is not the polymerization itself but obtaining the building blocks lactic acid (LA) and lactide, the actual cyclic monomer for polymerization. Although the synthesis of LA and the polymerization have been studied systematically, reports of lactide synthesis are scarce. Most lactide synthesis methods are described in patent literature, and current energy-intensive, aselective industrial processes are based on archaic scientific literature. This Review, therefore, highlights new methods with a technical comparison and description of the different approaches. Water-removal methodologies are compared, as this is a crucial factor in PLA production. Apart from the synthesis of lactide, this Review also emphasizes the use of chemically produced racemic lactic acid (esters) as a starting point in the PLA production scheme. Stereochemically tailored PLA can be produced according to such a strategy, giving access to various polymer properties. PMID:27071863

  16. Behavior of amino acids and peptides exposed in Earth orbit

    NASA Astrophysics Data System (ADS)

    Barbier, Bernard; Boillot, François; Chabin, Annie; Venet, Michel; Bure, Corinne; Jacquet, Romain; Bertrand-Urbaniak, Marylène; Brack, André

    2001-08-01

    In order to understand the chemical comportment of organic molecules of prebiotic interest when exposed to space conditions, amino acids, derivatives and peptides where exposed in Earth orbit during the CNES "Perseus-Exobiologie" mission. Dry films of samples were exposed free or associated with mineral powders to vacuum and to solar light down to 120 nm during three months outside the MIR station. After the mission, the remaining products were analyzed with respect of chemical degradation, racemization and polymerization. The analyses revealed a higher sensitivity of amino acids comparatively to peptides. The identification of by-products has allowed determining some photolysis pathways where decarboxylation and decarbonylation were found to be the major chemical reactions for amino acids and peptides, respectively. The study of associated minerals have shown that meteoritic powder was the most efficient to protect samples against UV light. The exposure of different peptides associated to meteorite powder of various thickness have allowed to determine that 5μm films were at least necessary to protect associated organics. Implications for the exogenous origin of organics are discussed.

  17. Stereospecificity of amino acid hydroxamate inhibition of aminopeptidases.

    PubMed

    Wilkes, S H; Prescott, J M

    1983-11-25

    Hydroxamates of amino acids and aliphatic acids are effective inhibitors of Aeromonas proteolytica amino-peptidase (EC 3.4.11.10) and of both the cytosolic (EC 3.4.11.1) and microsomal (EC 3.4.11.2) aminopeptidases of swine kidney. Cytosolic leucine aminopeptidase and the Aeromonas enzyme were inhibited to a greater extent by D isomers than by the L enantiomorphs, manganese-activated kidney cytosolic leucine aminopeptidase being inhibited 10 times more effectively by D-leucine and D-valine hydroxamic acids than by the L isomers. The D isomers of these two compounds inhibited Aeromonas aminopeptidase to an even greater extent with Ki values of 2 X 10(-9) and 5 X 10(-9), respectively, whereas the corresponding L isomers were bound 150 times less tightly. With the Aeromonas enzyme, a comparison of inhibition by racemic mixtures with that of the corresponding L isomers indicated that in all cases the contribution of the D isomer was predominant. Isocaproic hydroxamic acid inhibited this enzyme equally well as L-leucine hydroxamic acid, indicating that the amino group orientation in the D isomer contributes to the binding efficacy. Swine kidney microsomal aminopeptidase was also inhibited by D isomers of leucine and valine hydroxamic acids but in contrast to the other two enzymes, the inhibition was 10-fold less than that observed for the corresponding L isomers. Cytosolic leucine aminopeptidase with either 6 g atoms of zinc per mol or 12 g atoms of zinc per mol was inhibited only slightly by any of the hydroxamic acid compounds; evidently enzyme-bound manganese (or magnesium) is specific for hydroxamate binding to this aminopeptidase. PMID:6643439

  18. Peptide coupling between amino acids and the carboxylic acid of a functionalized chlorido-gold(I)-phosphane.

    PubMed

    Kriechbaum, Margit; List, Manuela; Himmelsbach, Markus; Redhammer, Günther J; Monkowius, Uwe

    2014-10-01

    We have developed a protocol for the direct coupling between methyl ester protected amino acids and the chlorido-gold(I)-phosphane (p-HOOC(C6H4)PPh2)AuCl. By applying the EDC·HCl/NHS strategy (EDC·HCl = N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide hydrochloride, NHS = N-hydroxysuccinimide), the methyl esters of l-phenylalanine, glycine, l-leucine, l-alanine, and l-methionine are coupled with the carboxylic acid of the gold complex in moderate to good yields (62-88%). All amino acid tagged gold complexes were characterized by (1)H and (13)C NMR spectroscopy and high-resolution mass spectrometry. As corroborated by measurement of the angle of optical rotation, no racemization occurred during the reaction. The molecular structure of the leucine derivative was determined by single-crystal X-ray diffraction. In the course of developing an efficient coupling protocol, the acyl chlorides (p-Cl(O)C(C6H4)PPh2)AuX (X = Cl, Br) were also prepared and characterized. PMID:25203269

  19. The Effects of Parent Body Processes on Amino Acids in Carbonaceous Chondrites

    NASA Technical Reports Server (NTRS)

    Glavin, Daniel P.; Callahan, Michael P.; Dworkin, Jason P.; Elsila, Jamie E.

    2010-01-01

    To investigate the effect of parent body processes on the abundance, distribution, and enantiomeric composition of amino acids in carbonaceous chondrites, the water extracts from nine different powdered Cl, CM, and CR carbonaceous chondrites were analyzed for amino acids by ultrahigh performance liquid chromatography-fluorescence detection and time-of-flight mass spectrometry (UPLC-FD/ToF-MS). Four aqueously altered type 1 carbonaceous chondrites including Orgueil (C11), Meteorite Hills (MET) 01070 (CM1), Scott Glacier (SCO) 06043 (CM1), and Grosvenor Mountains (GRO) 95577 (CR1) were analyzed using this technique for the first time. Analyses of these meteorites revealed low levels of two- to five-carbon acyclic amino alkanoic acids with concentrations ranging from -1 to 2,700 parts-per-billion (ppb). The type 1 carbonaceous chondrites have a distinct distribution of the five-carbon (C5) amino acids with much higher relative abundances of the gamma- and delta-amino acids compared to the type 2 and type 3 carbonaceous chondrites, which are dominated by a-amino acids. Much higher amino acid abundances were found in the CM2 chondrites Murchison, Lonewolf Nunataks (LON) 94102, and Lewis Cliffs (LEW) 90500, the CR2 Elephant Moraine (EET) 92042, and the CR3 Queen Alexandra Range (QUE) 99177. For example, a-aminoisobutyric acid ((alpha-AIB) and isovaline were approximately 100 to 1000 times more abundant in the type 2 and 3 chondrites compared to the more aqueously altered type 1 chondrites. Most of the chiral amino acids identified in these meteorites were racemic, indicating an extraterrestrial abiotic origin. However, non-racemic isovaline was observed in the aqueously altered carbonaceous chondrites Murchison, Orgueil, SCO 06043, and GRO 95577 with L-isovaline excesses ranging from approximately 11 to 19%, whereas the most pristine, unaltered carbonaceous chondrites analyzed in this study had no detectable L-isovaline excesses. These results are consistent with the

  20. Studies on the biodegradation of fosfomycin: synthesis of 13C-labeled intermediates, feeding experiments with Rhizobium huakuii PMY1, and isolation of labeled amino acids from cell mass by HPLC.

    PubMed

    McGrath, John W; Hammerschmidt, Friedrich; Kählig, Hanspeter; Wuggenig, Frank; Lamprecht, Günther; Quinn, John P

    2011-11-18

    Racemic (1R*,2R*)-1,2-dihydroxy-[1-(13)C(1)]propylphosphonic acid and 1-hydroxy-[1-(13)C(1)]acetone were synthesized and fed to R. huakuii PMY1. Alanine and a mixture of valine and methionine were isolated as their N-acetyl derivatives from the cell hydrolysate by reversed-phase HPLC and analyzed by NMR spectroscopy. It was found that the carbon atoms of the respective carboxyl groups were highly (13)C-labeled (up to 65 %). Hydroxyacetone is therefore considered an obligatory intermediate of the biodegradation of fosfomycin by R. huakuii PMY1. PMID:22012897

  1. Mechanistic studies of highly enantio- and diastereoselective aza-Petasis-Ferrier rearrangement catalyzed by chiral phosphoric acid.

    PubMed

    Terada, Masahiro; Komuro, Takazumi; Toda, Yasunori; Korenaga, Toshinobu

    2014-05-14

    The precise mechanism of the highly anti- and enantioselective aza-Petasis-Ferrier (APF) rearrangement of hemiaminal vinyl ethers catalyzed by a chiral phosphoric acid was investigated by undertaking experimental and theoretical studies. The APF rearrangement is characterized by the following unique mechanistic features: (i) efficient optical kinetic resolution of the starting racemic hemiaminal vinyl ether, (ii) enantioconvergent process from racemic hemiaminal vinyl ethers to optically active β-amino aldehyde products, and (iii) anomalous temperature effects on the enantioselectivity (enantioselectivity increases as reaction temperature increases). The following experiments were conducted to elucidate the unique mechanistic features as well as to uncover the overall scheme of the present rearrangement: (A) X-ray crystallographic analysis of the recovered hemiaminal vinyl ether to determine its absolute configuration, (B) rearrangements of enantiomerically pure hemiaminal vinyl ethers to validate the stereochemical relationship between the hemiaminal vinyl ethers and β-amino aldehydes, (C) theoretical studies on the transition states of the C-O bond cleavage and C-C bond formation steps to gain an insight into the optical kinetic resolution of the hemiaminal vinyl ether and the origin of the stereoselectivity, as well as to elucidate the overall scheme of the present rearrangement, and (D) crossover experiments of two hemiaminal vinyl ethers having different vinyl ether and aliphatic substituents to comprehend the mechanism of the anomalous temperature effect and the enantioconvergent process. The results of experiments and theoretical studies fully support the proposed mechanism of the present anti- and enantioselective APF rearrangement. PMID:24746095

  2. Roles of endothelial nitric oxide synthase (eNOS) and mitochondrial permeability transition pore (MPTP) in epoxyeicosatrienoic acid (EET)-induced cardioprotection against infarction in intact rat hearts.

    PubMed

    Gross, Garrett J; Hsu, Anna; Pfeiffer, Adam W; Nithipatikom, Kasem

    2013-06-01

    We previously demonstrated that 11,12 and 14,15-epoxeicosatrienoic acids (EETs) produce cardioprotection against ischemia-reperfusion injury in dogs and rats. Several signaling mechanisms have been implicated in the cardioprotective actions of the EETs; however, their mechanisms remain largely elusive. Since nitric oxide (NO) plays a significant role in cardioprotection and EETs have been demonstrated to induce NO production in various tissues, we hypothesized that NO is involved in mediating the EET actions in cardioprotection. To test this hypothesis, we used an in vivo rat model of infarction in which intact rat hearts were subjected to 30-min occlusion of the left coronary artery and 2-hr reperfusion. 11,12-EET or 14,15-EET (2.5mg/kg) administered 10min prior to the occlusion reduced infarct size, expressed as a percentage of the AAR (IS/AAR), from 63.9±0.8% (control) to 45.3±1.2% and 45.5±1.7%, respectively. A nonselective nitric oxide synthase (NOS) inhibitor, L-NAME (1.0mg/kg) or a selective endothelial NOS inhibitor, L-NIO (0.30mg/kg) alone did not affect IS/AAR but they completely abolished the cardioprotective effects of the EETs. On the other hand, a selective neuronal NOS inhibitor, nNOS I (0.03mg/kg) and a selective inducible NOS inhibitor, 1400W (0.10mg/kg) did not affect IS/AAR or block the cardioprotective effects of the EETs. Administration of 11,12-EET (2.5mg/kg) to the rats also transiently increased the plasma NO concentration. 14,15-EET (10μM) induced the phosphorylation of eNOS (Ser(1177)) as well as a transient increase of NO production in rat cardiomyoblast cell line (H9c2 cells). When 11,12-EET or 14,15-EET was administered at 5min prior to reperfusion, infarct size was also reduced to 42.8±2.2% and 42.6±1.9%, respectively. Interestingly, L-NAME (1.0mg/kg) and a mitochondrial KATP channel blocker, 5-HD (10mg/kg) did not abolish while a sarcolemmal KATP channel blocker, HMR 1098 (6.0mg/kg) and a mitochondrial permeability transition

  3. Amino acids as chiral auxiliaries in cyanuric chloride-based chiral derivatizing agents for enantioseparation by liquid chromatography.

    PubMed

    Batra, Sonika; Bhushan, Ravi

    2014-11-01

    This review summarizes and critically evaluates the recent research on application of amino acids and amino acid amides as chiral auxiliaries in cyanuric chloride (CC) based chiral derivatizing agents (CDRs), used in the indirect approach for enantiomeric resolution. Methods of synthesis of such CDRs, methods for synthesis of diastereomers of a variety of racemic compounds and parameters of liquid chromatographic separation, along with their prospects and their limitations in indirect enantioresolution, are discussed. Application of the said CDR(s) and the technical approach to be used that are discussed should be beneficial for control of enantiomeric purity in pharmaceutical industry, verification of enantiomeric ratio of commercial formulations and the development of methods for indirect resolution of a variety of chiral compounds. Derivatization methods are particularly required when a chromophore is to be introduced in low UV absorbing molecules, for their detection. PMID:25137358

  4. Enantioseparation of α-amino acids by means of Cinchona alkaloids as selectors in chiral ligand-exchange chromatography.

    PubMed

    Keunchkarian, Sonia; Franca, Carlos A; Gagliardi, Leonardo G; Castells, Cecilia B

    2013-07-12

    A conventional nonchiral column was used for the enantioseparation of several racemic α-amino acids (native and derivatized) through the use of Cinchona alkaloids as chiral selectors along with Cu(II) ions in chiral ligand-exchange chromatography. The mobile phase composition (i.e., the organic modifier content and pH) was studied in order to modulate retention and enantioselectivity. Good enantioseparation of many amino acids was obtained using equimolar amounts of Cu(II) and either cinchonidine, quinine or quinidine as chiral selectors in the mobile phase. The molecular geometry of the diastereomeric complexes formed was modeled and energetic differences between both compounds were calculated by methods based on semi-empirical force-field. Good correlations were obtained between experimental enantioselectivity factors and calculated energetic differences. PMID:23746371

  5. Improvement of catalytic activity of lipase in the presence of calix[4]arene valeric acid or hydrazine derivative.

    PubMed

    Akoz, Enise; Sayin, Serkan; Kaplan, Selcuk; Yilmaz, Mustafa

    2015-03-01

    Sol-gel encapsulation is a simple but powerful method to enhance the enantioselectivity of lipase-catalyzed transformations in an isooctane/aqueous buffer solution. Candida rugosa lipase was encapsulated according to a sol-gel procedure in the presence and absence of calix[4]arene hydrazine or carboxylic acid derivatives with Fe3O4 magnetic nanoparticles as an additive. The activity of the encapsulated lipases was evaluated for the enantioselective hydrolysis of racemic Naproxen methyl ester and the hydrolysis of p-Nitrophenylpalmitate. The results indicate that the encapsulated lipase without calix[4]arene derivative has lower conversion and enantioselectivity compared to the encapsulated lipase with calix[4]arene derivative. It was found that the calix[4]arene hydrazine and carboxylic acid-based encapsulated lipases have excellent activity and enantioselectivity (E >300) compared to encapsulated lipase without the calix[4]arene derivatives. PMID:25326059

  6. Preparative enantioseparation of propafenone by counter-current chromatography using di-n-butyl L-tartrate combined with boric acid as the chiral selector.

    PubMed

    Tong, Shengqiang; Shen, Mangmang; Zheng, Ye; Chu, Chu; Li, Xing-Nuo; Yan, Jizhong

    2013-09-01

    This paper extends the research of the utilization of borate coordination complexes in chiral separation by counter-current chromatography (CCC). Racemic propafenone was successfully enantioseparated by CCC with di-n-butyl l-tartrate combined with boric acid as the chiral selector. The two-phase solvent system was composed of chloroform/ 0.05 mol/L acetate buffer pH 3.4 containing 0.10 mol/L boric acid (1:1, v/v), in which 0.10 mol/L di-n-butyl l-tartrate was added in the organic phase. The influence of factors in the enantioseparation of propafenone were investigated and optimized. A total of 92 mg of racemic propafenone was completely enantioseparated using high-speed CCC in a single run, yielding 40-42 mg of (R)- and (S)-propafenone enantiomers with an HPLC purity over 90-95%. The recovery for propafenone enantiomers from fractions of CCC was in the range of 85-90%. PMID:23857918

  7. The Stereochemistry of Amino Acids In Carbonaceous Meteorites: Implications For Life's Origin

    NASA Astrophysics Data System (ADS)

    Engel, M. H.; Andrusevich, V. E.; Macko, S. A.

    Numerous processes have been proposed for the abiotic synthesis of organic com- pounds deemed essential for life's origin. However, none of these pathways for abiotic synthesis on Earth result in the stereochemistry that is observed for all life on Earth. All experiments utilizing abiotic syntheses for amino acids have produced racemic mixtures. Amino acid constituents of proteins in all living organisms are, however, al- most exclusively levorotary (L). We report the occurrence of L-amino acid enantiomer excesses in the hydrolyzed water extracts of two carbonaceous meteorites. Acid ex- tractions of the meteorite powders subsequent to water extraction resulted in the re- covery of even higher percentages of L-enantiomers relative to D-enantiomers. Amino acid distributions and stable isotope compositions support an extraterrestrial origin for these compounds rather than biological input subsequent to impact. Several common protein amino acids are entirely absent in the meteorite extracts and those that are present have stable isotope compositions outside of the range commonly observed for ancient and modern organic matter of biological origin on Earth. It is suggested that impact events during the Earth's early history may have provided organic compounds with the correct stereochemistry for life's origin.

  8. Amino acids

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002222.htm Amino acids To use the sharing features on this page, please enable JavaScript. Amino acids are organic compounds that combine to form proteins . ...

  9. Mefenamic Acid

    MedlinePlus

    Mefenamic acid is used to relieve mild to moderate pain, including menstrual pain (pain that happens before or during a menstrual period). Mefenamic acid is in a class of medications called NSAIDs. ...

  10. Aminocaproic Acid

    MedlinePlus

    Aminocaproic acid is used to control bleeding that occurs when blood clots are broken down too quickly. This type ... the baby is ready to be born). Aminocaproic acid is also used to control bleeding in the ...

  11. Ascorbic Acid

    MedlinePlus

    Ascorbic acid is used to prevent and treat scurvy, a disease caused by a lack of vitamin C in ... Ascorbic acid comes in extended-release (long-acting) capsules and tablets, lozenges, syrup, chewable tablets, and liquid drops to ...

  12. Acid mucopolysaccharides

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003368.htm Acid mucopolysaccharides To use the sharing features on this page, please enable JavaScript. Acid mucopolysaccharides is a test that measures the amount ...

  13. Ethacrynic Acid

    MedlinePlus

    Ethacrynic acid, a 'water pill,' is used to treat swelling and fluid retention caused by various medical problems. It ... Ethacrynic acid comes as a tablet to take by mouth. It is usually taken once or twice a day ...

  14. A comparative study of the hydroxy acids from the Murchison, GRA 95229 and LAP 02342 meteorites

    NASA Astrophysics Data System (ADS)

    Pizzarello, Sandra; Wang, Yi; Chaban, Galina M.

    2010-11-01

    The hydroxy acid suites extracted from the Murchison (MN), GRA 95229 (GRA) and LAP 02342 (LAP) meteorites have been investigated for their molecular, chiral and isotopic composition. Substantial amounts of the compounds have been detected in all three meteorites, with a total abundance that is lower than that of the amino acids in the same stones. Overall, their molecular distributions mirror closely that of the corresponding amino acids and most evidently so for the LAP meteorite. A surprising L-lactic acid enantiomeric excess was found present in all three stones, which cannot be easily accounted by terrestrial contamination; all other compounds of the three hydroxy acid suites were found racemic. The branched-chain five carbon and the diastereomer six-carbon hydroxy acids were also studied vis-a-vis the corresponding amino acids and calculated ab initio thermodynamic data, with the comparison allowing the suggestion that meteoritic hydroxyacid at these chain lengths formed under thermodynamic control and, possibly, at a later stage than the corresponding amino acids. 13C and D isotopic enrichments were detected for many of the meteoritic hydroxy acids and found to vary between molecular species with trends that also appear to correlate to those of amino acids; the highest δD value (+3450‰) was displayed by GRA 2-OH-2-methylbutyric acid. The data suggest that, while the amino- and hydroxy acids likely relate to common presolar precursor, their final distribution in meteorites was determined to large extent by the overall composition of the environments that saw their formation, with ammonia being the determining factor in their final abundance ratios.

  15. Enantioselective Utilization of D-Amino Acids by Deep-Sea Microorganisms

    PubMed Central

    Kubota, Takaaki; Kobayashi, Tohru; Nunoura, Takuro; Maruyama, Fumito; Deguchi, Shigeru

    2016-01-01

    Microorganisms that utilize various D-amino acids (DAAs) were successfully isolated from deep-sea sediments. The isolates were phylogenetically assigned to Alphaproteobacteria, Gammmaproteobacteria, and Bacilli. Some of the isolates exhibited high enantioselective degradation activities to various DAAs. In particular, the Alphaproteobacteria Nautella sp. strain A04V exhibited robust growth in minimal medium supplemented with D-Val as a sole carbon and nitrogen source, whereas its growth was poor on minimal medium supplemented with L-Val instead of D-Val. Its growth was facilitated most when racemic mixtures of valine were used. In contrast, the Nautella strains isolated from shallow-sea grew only with L-Val. No significant differences were found among the strains in the genome sequences including genes possibly related to DAA metabolisms. PMID:27148200

  16. Open-tubular electrochromatographic chiral separation of amino acids using an organic nanocrystals immobilized capillary.

    PubMed

    Kitagawa, Fumihiko; Sudaki, Hiroshi; Sueyoshi, Kenji; Otsuka, Koji

    2013-01-01

    The preparation of cinchonidine (CCND) nanocrystals and their immobilization onto the inner surface of a fused silica capillary was investigated for use in the enantioseparation by capillary electrochromatography. The CCND nanocrystals were prepared by an emulsion method that utilizes crystal growth in an oil-in-water emulsion without a stabilizer. As a result, white-colored aqueous dispersions of organic nanoparticles were obtained. SEM images showed that the prepared CCND nanocrystals were from 300 to 700 nm in size. When the obtained dispersion was introduced into a poly(diallyldimethylammonium chloride) (PDDAC) coated capillary, the nanocrystals were strongly adsorbed onto the inner surface due to an electrostatic interaction between cationic PDDAC and the negatively charged organic nanocrystals. In CCND nanocrystals coated capillary, CEC enantioseparations of racemic amino acids were successfully achieved. The reproducibilities of the detection times were acceptable with a relative standard deviation of less than 7%, indicating that stable nanocrystal coating could be obtained by our proposed method. PMID:23303094

  17. Antiparasitic activity of prenylated benzoic acid derivatives from Piper species.

    PubMed

    Flores, Ninoska; Jiménez, Ignacio A; Giménez, Alberto; Ruiz, Grace; Gutiérrez, David; Bourdy, Genevieve; Bazzocchi, Isabel L

    2009-03-01

    Fractionation of dichloromethane extracts from the leaves of Piper heterophyllum and P. aduncum afforded three prenylated hydroxybenzoic acids, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid, 3-[(2E,6E,10E)-11-carboxy-13-hydroxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl]-4,5-dihydroxybenzoic acid and 3-[(2E,6E,10E)-11-carboxy-14-hydroxy-3,7,15-trimethyl-2,6,10,15-hexadecatetraenyl]-4,5-dihydroxybenzoic acid, along with the known compounds, 4,5-dihydroxy-3-(E,E,E-11-formyl-3,7,15-trimethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid (arieianal), 3,4-dihydroxy-5-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 4-hydroxy-3-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid, 4-hydroxy-3-(3,7-dimethyl-2,6-octadienyl)benzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, HSQC and HMBC) and comparison with data reported in the literature. Riguera ester reactions and optical rotation measurements established the compounds as racemates. The antiparasitic activity of the compounds were tested against three strains of Leishmania spp., Trypanosoma cruzi and Plasmodium falciparum. The results showed that 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid exhibited potent and selective activity against L. braziliensis (IC(50) 6.5 microg/ml), higher that pentamidine used as control. Moreover, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl- 2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid showed moderate antiplasmodial (IC(50) 3.2 microg/ml) and trypanocidal (16.5 microg/ml) activities, respectively. PMID:19361822

  18. Extraterrestrial Amino Acids in the Almahata Sitta Meteorite

    NASA Astrophysics Data System (ADS)

    Callahan, Michael; Aubrey, A.; Bada, J. L.; Dworkin, J. P.; Elsila, J. E.; Glavin, D. P.; Parker, E.; Jenniskens, P.

    2009-09-01

    The recovery of meteorite fragments from the 2008 TC3 asteroid impact, collectively named Almahata Sitta, revealed a rare, anomalous polymict ureilite containing large carbonaceous grains (Jenniskens et al. 2009). Here we report the first amino acid analysis of a meteorite from an F-type asteroid as part of the Almahata Sitta meteorite sample analysis consortium. A single fragment (piece #4, 1.2 grams) was crushed to a powder, and separate 0.1 g aliquots of the same meteorite were carried through identical hot-water extraction, acid hydrolysis and desalting procedures at NASA Goddard Space Flight Center and the Scripps Institution of Oceanography. The o-phthaldialdehyde/N-acetyl-L-cysteine amino acid derivatives in the extracts were analyzed by high performance liquid chromatography with UV fluorescence detection and time-of-flight mass spectrometry. Analyses of the meteorite extracts revealed a complex distribution of two- to six-carbon aliphatic amino acids with abundances ranging from 0.5 to 69 parts-per-billion (ppb). Glycine was the most abundant amino acid detected, however, since this protein amino acid is a common terrestrial contaminant, we are currently unable to rule out at least a partial terrestrial source. However, the D/L ratio of alanine in the meteorite was racemic, suggesting that very little terrestrial amino acid contamination. Several non-protein amino acids that are rare in the biosphere were also identified in the meteorite above background levels including D,L-4-amino-2-methybutyric acid (65 ± 8 ppb), D-isovaline (1.3 ± 0.1 ppb), L-isovaline (1.4 ± 0.1 ppb), and α-aminoisobutryic acid (7.1 ± 5.8 ppb). The abundance of isovaline and AIB are 1000 times lower than the abundances found in the CM2 meteorite Murchison while D,L-4-amino-2-methybutyric acid is similar. The very low amino acid abundances and the presence of several amino acid decomposition products including methylamine, ethylamine, and isopropylamine are consistent with

  19. Lipoic acid stimulates cAMP production via G protein-coupled receptor-dependent and -independent mechanisms.

    PubMed

    Salinthone, Sonemany; Schillace, Robynn V; Tsang, Catherine; Regan, John W; Bourdette, Dennis N; Carr, Daniel W

    2011-07-01

    Lipoic acid (LA) is a naturally occurring fatty acid that exhibits anti-oxidant and anti-inflammatory properties and is being pursued as a therapeutic for many diseases including multiple sclerosis, diabetic polyneuropathy and Alzheimer's disease. We previously reported on the novel finding that racemic LA (50:50 mixture of R-LA and S-LA) stimulates cAMP production, activates prostanoid EP2 and EP4 receptors and adenylyl cyclases (AC), and suppresses activation and cytotoxicity in NK cells. In this study, we present evidence that furthers our understanding of the mechanisms of action of LA. Using various LA derivatives, such as dihydrolipoic acid (DHLA), S,S-dimethyl lipoic acid (DMLA) and lipoamide (LPM), we discovered that only LA is capable of stimulating cAMP production in NK cells. Furthermore, there is no difference in cAMP production after stimulation with either R-LA, S-LA or racemic LA. Competition and synergistic studies indicate that LA may also activate AC independent of the EP2 and EP4 receptors. Pretreatment of PBMCs with KH7 (a specific peptide inhibitor of soluble AC) and the calcium inhibitor (Bapta) prior to LA treatment resulted in reduced cAMP levels, suggesting that soluble AC and calcium signaling mediate LA stimulation of cAMP production. In addition, pharmacological inhibitor studies demonstrate that LA also activates other G protein-coupled receptors, including histamine and adenosine but not the β-adrenergic receptors. These novel findings provide information to better understand the mechanisms of action of LA, which can help facilitate the use of LA as a therapeutic for various diseases. PMID:21036588

  20. Valproic Acid

    MedlinePlus

    Valproic acid is used alone or with other medications to treat certain types of seizures. Valproic acid is also used to treat mania (episodes of ... to relieve headaches that have already begun. Valproic acid is in a class of medications called anticonvulsants. ...

  1. Preparation of molecularly imprinted cross-linked chitosan/glutaraldehyde resin for enantioselective separation of L-glutamic acid.

    PubMed

    Monier, M; El-Sokkary, A M A

    2010-08-01

    In the present study, separation of L-glutamic acid from dilute aqueous solution by solid-phase extraction based on molecular imprinting technique using cross-linked chitosan/glutaraldehyde resin was investigated. L-Glutamic acid imprinted cross-linked chitosan (LGIC) was prepared by cross-linking of chitosan by glutaraldehyde cross-linker, in the presence of L-glutamic acid. Non-imprinted cross-linked chitosan (NIC) as control was also prepared by the same procedure in the absence of template molecules. The morphological structures of both LGIC and NIC were examined by scanning electron microscope (SEM). LGIC particles were applied to determine the optimum operational condition for l-glutamic acid separation from dilute aqueous solution. In adsorption step, optimum pH and retention time were 5.5 and 100 min, while corresponding values in extraction step were 2.5 and 60 min, respectively. The adsorption isotherms indicated that the maximum adsorption capacities of L- and D-glutamic acid on LGIC were 42+/-0.8 and 26+/-1.2mg/g, respectively, while in case of NIC, both L- and D-glutamic acid present the same maximum adsorption capacity 7+/-0.6 mg/g, which confirm that the molecular imprinting technique creates an enantioselectivity of LGIC toward L-glutamic acid. In addition, chiral resolution of l-, d-glutamic acid racemic mixture was carried out using column of LGIC. PMID:20441776

  2. Amino acid residues controlling reactivation of organophosphonyl conjugates of acetylcholinesterase by mono- and bisquaternary oximes

    SciTech Connect

    1995-03-17

    Single and multiple site mutants of recombinant mouse acetyicholinesterase (rMoAChE) were inhibited with racemic 7-(methylethoxyphosphinyloxy) -1-methylquinolinium iodide (MEPO) and the resulting mixture.

  3. Fatty acids - trans fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The data supporting a negative effect of dietary trans fatty acids on cardiovascular disease risk is consistent. The primary dietary sources of trans fatty acids include partially hydrogenated fat and rudiment fat. The adverse effect of trans fatty acids on plasma lipoprotein profiles is consisten...

  4. The Efficacy and Safety of Evekeo, Racemic Amphetamine Sulfate, for Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms: A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled Crossover Laboratory Classroom Study

    PubMed Central

    Brams, Matthew; Cutler, Andrew J.; Kollins, Scott H.; Northcutt, Jo; Padilla, Americo; Turnbow, John M.

    2015-01-01

    Abstract Objective: The study goal was to determine the efficacy and safety of an optimal dose of Evekeo, racemic amphetamine sulfate, 1:1 d-amphetamine and l-amphetamine (R-AMPH), compared to placebo in treating children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. Methods: A total of 107 children ages 6–12 years were enrolled in this multicenter, dose-optimized, randomized, double-blind, placebo-controlled crossover study. After 8 weeks of open-label dose optimization, 97 subjects were randomized to 2 weeks of double-blind treatment in the sequence of R-AMPH followed by placebo (n=47) or placebo followed by R-AMPH (n=50). Efficacy measures included the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) administered predose and at 0.75, 2, 4, 6, 8, and 10 hours postdose on 2 laboratory classroom days. Safety assessments included physical examination, chemistry, hematology, vital signs, and treatment-emergent adverse events (TEAEs). Results: Compared to placebo, a single daily dose of R-AMPH significantly improved SKAMP-Combined scores (p<0.0001) at each time point tested throughout the laboratory classroom days, with effect onset 45 minutes postdose and extending through 10 hours. R-AMPH significantly improved PERMP number of problems attempted and correct (p<0.0001) throughout the laboratory classroom days. During the twice-daily dose-optimization open-label phase, improvements were observed with R-AMPH in scores of the ADHD-Rating Scale IV and Clinical Global Impressions Severity and Improvement Scales. TEAEs and changes in vital signs associated with R-AMPH were generally mild and not unexpected. The most common TEAEs in the open-label phase were decreased appetite (27.6%), upper abdominal pain (14.3%), irritability (14.3%), and headache (13.3%). Conclusions: Compared to placebo, R-AMPH was effective in treating children aged 6–12 years with ADHD

  5. Response of Cultured Maize Cells to (+)-Abscisic Acid, (-)-Abscisic Acid, and Their Metabolites.

    PubMed Central

    Balsevich, J. J.; Cutler, A. J.; Lamb, N.; Friesen, L. J.; Kurz, E. U.; Perras, M. R.; Abrams, S. R.

    1994-01-01

    The metabolism and effects of (+)-S- and (-)-R-abscisic acid (ABA) and some metabolites were studied in maize (Zea mays L. cv Black Mexican Sweet) suspension-cultured cells. Time-course studies of metabolite formation were performed in both cells and medium via analytical high-performance liquid chromatography. Metabolites were isolated and identified using physical and chemical methods. At 10 [mu]M concentration and 28[deg] C, (+)-ABA was metabolized within 24 h, yielding natural (-)-phaseic acid [(-)-PA] as the major product. The unnatural enantiomer (-)-ABA was less than 50% metabolized within 24 h and gave primarily (-)-7[prime]-hydroxyABA [(-)-7[prime]-HOABA], together with (+)-PA and ABA glucose ester. The distribution of metabolites in cells and medium was different, reflecting different sites of metabolism and membrane permeabilities of conjugated and nonconjugated metabolites. The results imply that (+)-ABA was oxidized to (-)-PA inside the cell, whereas (-)-ABA was converted to (-)-7[prime]-HOABA at the cell surface. Growth of maize cells was inhibited by both (+)- and (-)-ABA, with only weak contributions from their metabolites. The concentration of (+)-ABA that caused a 50% inhibition of growth of maize cells was approximately 1 [mu]M, whereas that for its metabolite (-)-PA was approximately 50 [mu]M. (-)-ABA was less active than (+)-ABA, with 50% growth inhibition observed at about 10 [mu]M. (-)-7[prime]-HOABA was only weakly active, with 50% inhibition caused by approximately 500 [mu]M. Time-course studies of medium pH indicated that (+)-ABA caused a transient pH increase (+0.3 units) at 6 h after addition that was not observed in controls or in samples treated with (-)-PA. The effect of (-)-ABA on medium Ph was marginal. No racemization at C-1[prime] of (+)-ABA, (-)-ABA, or metabolites was observed during the studies. PMID:12232311

  6. Direct dating of human fossils.

    PubMed

    Grün, Rainer

    2006-01-01

    The methods that can be used for the direct dating of human remains comprise of radiocarbon, U-series, electron spin resonance (ESR), and amino acid racemization (AAR). This review gives an introduction to these methods in the context of dating human bones and teeth. Recent advances in ultrafiltration techniques have expanded the dating range of radiocarbon. It now seems feasible to reliably date bones up to 55,000 years. New developments in laser ablation mass spectrometry permit the in situ analysis of U-series isotopes, thus providing a rapid and virtually non-destructive dating method back to about 300,000 years. This is of particular importance when used in conjunction with non-destructive ESR analysis. New approaches in AAR analysis may lead to a renaissance of this method. The potential and present limitations of these direct dating techniques are discussed for sites relevant to the reconstruction of modern human evolution, including Florisbad, Border Cave, Tabun, Skhul, Qafzeh, Vindija, Banyoles, and Lake Mungo. PMID:17103430

  7. Chiral quizalofop-ethyl and its metabolite quizalofop-acid in soils: Enantioselective degradation, enzymes interaction and toxicity to Eisenia foetida.

    PubMed

    Ma, Lin; Liu, Hui; Qu, Han; Xu, Yangguang; Wang, Peng; Sun, Mingjing; Zhou, Zhiqiang; Liu, Donghui

    2016-06-01

    An enantioselective chromatographic method to analyze enantiomers of quizalofop-ethyl and its metabolite quizalofop-acid was established using a high-performance liquid chromatography (HPLC) on (R, R) Whelk-O 1 column. The enantioselective degradation kinetics of quizalofop-ethyl and quizalofop-acid in three soils were investigated. Moreover, the interaction with urease and catalase in the soils and the acute toxicity to Eisenia foetida of quizalofop-ethyl were also determined in order to assess their metabolism mechanism and environmental risk. From the results, quizalofop-ethyl was configurationally stable and was hydrolyzed rapidly to quizalofop-acid, which also degraded enantioselectively but slowly, and the inversion of the S-(-)-quizalofop-acid into the R-(+)-quizalofop-acid was observed in Xinxiang soil. In addition, quizalofop-ethyl and quizalofop-acid enantioselectively affected urease activity but not catalase. The acute toxicity assays to earthworm indicated that the racemic quizalofop-ethyl and quizalofop-acid were more toxic than quizalofop-p-ethyl and quizalofop-p-acid respectively, dramatically, the toxicity of the metabolite was much higher than the parent compound. These results revealed the enantioselective degradation of quizalofop-ethyl and quizalofop-acid, and the differences of toxicity among the enantiomers of the parent compound and the metabolite, which should be considered in future environmental risk evaluation. PMID:26971169

  8. Acid Deposition

    EPA Science Inventory

    This indicator presents acid deposition trends in the contiguous U.S. from 1989 to 2007. Data are broken down by wet and dry deposition and deposition of nitrogen and sulfur compounds. Acid deposition is particularly damaging to lakes, streams, and forests and the plants and a...

  9. Acid rain

    SciTech Connect

    White, J.C. )

    1988-01-01

    This book presents the proceedings of the third annual conference sponsored by the Acid Rain Information Clearinghouse (ARIC). Topics covered include: Legal aspects of the source-receptor relationship: an energy perspective; Scientific uncertainty, agency inaction, and the courts; and Acid rain: the emerging legal framework.

  10. Acid rain

    SciTech Connect

    Elsworth, S.

    1985-01-01

    This book was written in a concise and readable style for the lay public. It's purpose was to make the public aware of the damage caused by acid rain and to mobilize public opinion to favor the elimination of the causes of acid rain.

  11. Acid rain

    SciTech Connect

    Sweet, W.

    1980-06-20

    Acid precipitation includes not only rain but also acidified snow, hail and frost, as well as sulfur and nitrogen dust. The principal source of acid precipitation is pollution emitted by power plants and smelters. Sulfur and nitrogen compounds contained in the emissions combine with moisture to form droplets with a high acid content - sometimes as acidic as vinegar. When sufficiently concentrated, these acids can kill fish and damage material structures. Under certain circumstances they may reduce crop and forest yields and cause or aggravate respiratory diseases in humans. During the summer, especially, pollutants tend to collect over the Great Lakes in high pressure systems. Since winds typically are westerly and rotate clockwise around high pressure systems, the pollutants gradually are dispersed throughout the eastern part of the continent.

  12. Asparagusic acid.

    PubMed

    Mitchell, Stephen C; Waring, Rosemary H

    2014-01-01

    Asparagusic acid (1,2-dithiolane-4-carboxylic acid) is a simple sulphur-containing 5-membered heterocyclic compound that appears unique to asparagus, though other dithiolane derivatives have been identified in non-food species. This molecule, apparently innocuous toxicologically to man, is the most probable culprit responsible for the curious excretion of odorous urine following asparagus ingestion. The presence of the two adjacent sulphur atoms leads to an enhanced chemical reactivity, endowing it with biological properties including the ability to substitute potentially for α-lipoic acid in α-keto-acid oxidation systems. This brief review collects the scattered data available in the literature concerning asparagusic acid and highlights its properties, intermediary metabolism and exploratory applications. PMID:24099657

  13. [Gastric Acid].

    PubMed

    Ruíz Chávez, R

    1996-01-01

    Gastric acid, a product of parietal cells secretion, full fills multiple biological roles which are absolutely necessary to keep corporal homeostasis. The production of the acid depends upon an effector cellular process represented in the first step by histamine, acetilcholine and gastrin, first messengers of the process. These interact with specific receptors than in sequence activate second messengers -cAMP and the calcium-calmodulin system- which afterwards activate a kinase. An specific protein is then phosphorilated by this enzyme, being the crucial factor that starts the production of acid. Finally, a proton bomb, extrudes the acid towards the gastric lumen. The secretion process mentioned above, is progressive lyactivated in three steps, two of which are stimulators -cephalic and gastric phases- and the other one inhibitor or intestinal phase. These stages are started by mental and neurological phenomena -thought, sight, smell or memory-; by food, drugs or other ingested substances; and by products of digestion. Changes in regulation of acid secretion, in the structure of gastro-duodenal mucosal barrier by a wide spectrum of factors and agents including food, drugs and H. pylori, are the basis of acid-peptic disease, entity in which gastric acid plays a fundamental role. From the therapeutic point of view, so at the theoretical as at the practical levels, t is possible to interfere with the secretion of acid by neutralization of some of the steps of the effector cellular process. An adequate knowledge of the basics related to gastric acid, allows to create strategies for the clinical handling of associated pathology, specifically in relation to peptic acid disease in all of the known clinical forms. PMID:12165790

  14. Degradation of CYANEX 301 in Contact with Nitric Acid Media

    SciTech Connect

    Philippe Marc; Radu Custelcean; Gary S. Groenewold; John R. Klaehn; Dean R. Peterman; Laetitia H. Delmau

    2012-10-01

    The nature of the degradation product obtained upon contacting CYANEX 301 (bis(2,4,4-trimethylpentyl)dithiophosphinic acid) with nitric acid has been elucidated and found to be a disulfide derivative. The first step to the degradation of CYANEX 301 in toluene has been studied using 31P{1H} NMR after being contacted with nitric acid media. The spectrum of the degradation product exhibits a complex multiplet around dP = 80 ppm. A succession of purifications of CYANEX 301 has resulted in single crystals of the acidic form and the corresponding ammonium salt. Unlike the original CYANEX 301, which consists of a complex diastereomeric mixture displaying all possible combinations of chiral orientations at the 2-methyl positions, the purified crystals were shown by single-crystal X-ray diffraction to be racemates, containing 50:50 mixtures of the [R;R] and [S;S] diastereomers. The comparison between the 31P {1H} NMR spectra of the degradation products resulting from the diastereomerically pure CYANEX 301 and the original diastereomeric mixture has elucidated the influence of the isomeric composition on the multiplicity of the 31P {1H} NMR peak. These NMR data indicate the initial degradation leads to a disulfide-bridged condensation product displaying multiple resonances due to phosphorus–phosphorus coupling, which is caused by the inequivalence of the two P atoms as a result of their different chirality. A total of nine different NMR resonances, six of which display phosphorus–phosphorus coupling, could be assigned, and the identity of the peaks corresponding to phosphorus atoms coupled to each other was confirmed by 31P {1H} homodecoupled NMR analysis.

  15. Reactivity of alanylalanine diastereoisomers in neutral and acid aqueous solutions: a versatile stereoselectivity.

    PubMed

    Plasson, Raphaël; Tsuji, Maika; Kamata, Masazumi; Asakura, Kouichi

    2011-10-01

    A good comprehension of the reactivity of peptides in aqueous solution is fundamental in prebiotic chemistry, namely for understanding their stability and behavior in primitive oceans. Relying on the stereoselectivity of the involved reactions, there is a huge interest in amino acid derivatives for explaining the spontaneous emergence of homochirality on primitive Earth. The corresponding kinetic and thermodynamic parameters are however still poorly known in the literature. We studied the reactivity of alanylalanine in acidic to neutral conditions as a model system. The hydrolysis into amino acids, the epimerization of the N-terminal residue, and the cyclization into diketopiperazine could be successfully identified and studied. This kinetic investigation highlighted interesting behaviors. Complex mechanisms were observed in very acidic conditions. The relative kinetic stability of the diastereoisomers of the dipeptide is highly dependent of the pH, with the possibility to dynamically destabilize the thermodynamically more stable diastereoisomers. The existence of the cyclization of dipeptides adds complexity to the system. On one hand it brings additional stereoselectivities; on the other hand fast racemization of heterochiral dipeptides is obtained. PMID:21562847

  16. Primordial synthesis of amines and amino acids in a 1958 Miller H2S-rich spark discharge experiment.

    PubMed

    Parker, Eric T; Cleaves, Henderson J; Dworkin, Jason P; Glavin, Daniel P; Callahan, Michael; Aubrey, Andrew; Lazcano, Antonio; Bada, Jeffrey L

    2011-04-01

    Archived samples from a previously unreported 1958 Stanley Miller electric discharge experiment containing hydrogen sulfide (H(2)S) were recently discovered and analyzed using high-performance liquid chromatography and time-of-flight mass spectrometry. We report here the detection and quantification of primary amine-containing compounds in the original sample residues, which were produced via spark discharge using a gaseous mixture of H(2)S, CH(4), NH(3), and CO(2). A total of 23 amino acids and 4 amines, including 7 organosulfur compounds, were detected in these samples. The major amino acids with chiral centers are racemic within the accuracy of the measurements, indicating that they are not contaminants introduced during sample storage. This experiment marks the first synthesis of sulfur amino acids from spark discharge experiments designed to imitate primordial environments. The relative yield of some amino acids, in particular the isomers of aminobutyric acid, are the highest ever found in a spark discharge experiment. The simulated primordial conditions used by Miller may serve as a model for early volcanic plume chemistry and provide insight to the possible roles such plumes may have played in abiotic organic synthesis. Additionally, the overall abundances of the synthesized amino acids in the presence of H(2)S are very similar to the abundances found in some carbonaceous meteorites, suggesting that H(2)S may have played an important role in prebiotic reactions in early solar system environments. PMID:21422282

  17. Primordial Synthesis of Amines and Amino Acids in a 1958 Miller H2S-Rich Spark Discharge Experiment

    NASA Technical Reports Server (NTRS)

    Parker, Eric T.; Cleaves, Henderson J.; Dworkin, Jason P.; Glavin, Daniel P.; Callahan, Michael; Aubrey, Andrew; Lazcano, Antonio; Bada, Jeffrey L.

    2011-01-01

    Archived samples from a previously unreported 1958 Stanley Miller electric discharge experiment containing hydrogen sulfide (H2S) were recently discovered and analyzed using high-performance liquid chromatography and time-of-flight mass spectrometry. We report here the detection and quantification of primary amine-containing compounds in the original sample residues, which were produced via spark discharge using a gaseous mixture of H2S, CH4, NH3, and CO2. A total of 23 amino acids and 4 amines, including 7 organosulfur compounds, were detected in these samples. The major amino acids with chiral centers are racemic within the accuracy of the measurements, indicating that they are not contaminants introduced during sample storage. This experiment marks the first synthesis of sulfur amino acids from spark discharge experiments designed to imitate primordia! environments. The relative yield of some amino acids, in particular the isomers of aminobutyric acid, are the highest ever found in a spark discharge experiment. The simulated primordial conditions used by Miller may serve as a model for early volcanic plume chemistry and provide insight to the possible roles such plumes may have played in abiotic organic synthesis. Additionally, the overall abundances of the synthesized amino acids in the presence of H2S are very similar to the abundances found in some carbonaceous meteorites, suggesting that H2S may have played an important role in prebiotic reactions in early solar system environments.

  18. Evaluation of a new protocol for enzymatic dynamic kinetic resolution of 3-hydroxy-3-(aryl)propanoic acids.

    PubMed

    Koszelewski, Dominik; Zysk, Małgorzata; Brodzka, Anna; Żądło, Anna; Paprocki, Daniel; Ostaszewski, Ryszard

    2015-12-01

    The application of tandem metal-enzyme dynamic kinetic resolution (DKR) is a powerful tool for the manufacture of high-value chemical commodities. A new protocol of kinetic resolution based on irreversible enzymatic esterification of carboxylic acids with orthoesters was introduced to obtain optically active β-hydroxy esters. This procedure was combined with metal catalyzed racemization of the target substrate providing both (R) and (S) enantiomers of ethyl 3-hydroxy-3-(4-nitrophenyl)propanoate with a high yield of 89% at 40 °C. A substantial influence of the enzyme type, organic co-solvent, and metal catalyst on the conversion and enantioselectivity of the enzymatic dynamic kinetic resolution was noted. PMID:26383530

  19. Acid fog

    SciTech Connect

    Hileman, B.

    1983-03-01

    Fog in areas of southern California previously thought to be pollution-free has been shown to have a pH as low as 1.69. It has been found to be most acidic after smoggy days, suggesting that it forms on the aerosol associated with the previously exiting smog. Studies on Whiteface Mountain in the Adirondacks show that fog water is often 10 times as acidic as rainwater. As a result of their studies, California plans to spend $4 million on acid deposition research in the coming year. (JMT)

  20. Exclusive Stereocomplex Crystallization of Linear and Multiarm Star-Shaped High-Molecular-Weight Stereo Diblock Poly(lactic acid)s.

    PubMed

    Han, Lili; Shan, Guorong; Bao, Yongzhong; Pan, Pengju

    2015-11-01

    Linear, 3-arm, and 6-arm star-shaped stereo diblock copolymers of l- and d-lactic acid (PLLA-b-PDLA) with high molecular weights (MWs) were synthesized via two-step ring-opening polymerization (ROP) with 1-dodechanol, glycerol, and d-sorbitol as the initiators, respectively. The chemical structure, nonisothermal and isothermal crystallization kinetics, crystalline structure, lamellar morphology, and mechanical thermal properties of PLLA-b-PDLAs with different macromolecular topologies were investigated. Compared to the high-molecular-weight (MW) poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) racemic blends, PLLA-b-PDLAs exhibit faster crystallization upon cooling and isothermal melt crystallization; they crystallize exclusively in stereocomplex (sc) crystallites under all of the conditions investigated. This is attributable to the enhanced interactions between enantiomeric blocks linked covalently. Macromolecular topology influences the crystallization kinetics and crystalline structure of PLLA-b-PDLAs significantly. The crystallization temperature upon cooling, melting temperature, degree of crystallinity, spherulitic growth rate, crystallite size, long period, and crystalline layer thickness of PLLA-b-PDLA decrease with increasing branching number because of the retarding effect of branching on the crystallization rate and crystallizability. Because of the formation of high-melting-point sc crystallites, both the linear and star-shaped PLLA-b-PDLAs exhibit better thermal resistance and higher storage moduli at high temperature than does homocrystalline PLLA. PMID:26457767

  1. Folic acid

    MedlinePlus

    ... in the blood vessel to keep it open. Bipolar disorder. Taking folic acid does not appear to improve the antidepressant effects of lithium in people with bipolar disorder. However, taking folate with the medication valproate improves ...

  2. Mefenamic Acid

    MedlinePlus

    ... as mefenamic acid may cause ulcers, bleeding, or holes in the stomach or intestine. These problems may ... like coffee grounds, blood in the stool, or black and tarry stools.Keep all appointments with your ...

  3. ACID RAIN

    EPA Science Inventory

    Acid precipitation has become one of the major environmental problems of this decade. It is a challenge to scientists throughout the world. Researchers from such diverse disciplines as plant pathology, soil science, bacteriology, meteorology and engineering are investigating diff...

  4. Acid Precipitation

    ERIC Educational Resources Information Center

    Likens, Gene E.

    1976-01-01

    Discusses the fact that the acidity of rain and snow falling on parts of the U.S. and Europe has been rising. The reasons are still not entirely clear and the consequences have yet to be well evaluated. (MLH)

  5. Carnosic acid.

    PubMed

    Birtić, Simona; Dussort, Pierre; Pierre, François-Xavier; Bily, Antoine C; Roller, Marc

    2015-07-01

    Carnosic acid (salvin), which possesses antioxidative and antimicrobial properties, is increasingly exploited within the food, nutritional health and cosmetics industries. Since its first extraction from a Salvia species (∼70 years ago) and its identification (∼50 years ago), numerous articles and patents (∼400) have been published on specific food and medicinal applications of Rosmarinus and Salvia plant extracts abundant in carnosic acid. In contrast, relevant biochemical, physiological or molecular studies in planta have remained rare. In this overview, recent advances in understanding of carnosic acid distribution, biosynthesis, accumulation and role in planta, and its applications are summarised. We also discuss the deficiencies in our understanding of the relevant biochemical processes, and suggest the molecular targets of carnosic acid. Finally, future perspectives and studies related to its potential roles are highlighted. PMID:25639596

  6. Aminocaproic Acid

    MedlinePlus

    Amicar® Oral Solution ... Aminocaproic acid comes as a tablet and a solution (liquid) to take by mouth. It is usually ... it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away ...

  7. Tranexamic Acid

    MedlinePlus

    ... is used to treat heavy bleeding during the menstrual cycle (monthly periods) in women. Tranexamic acid is in ... tablets for more than 5 days in a menstrual cycle or take more than 6 tablets in a ...

  8. Acidic precipitation

    SciTech Connect

    Martin, H.C.

    1987-01-01

    At the International Symposium on Acidic Precipitation, over 400 papers were presented, and nearly 200 of them are included here. They provide an overview of the present state of the art of acid rain research. The Conference focused on atmospheric science (monitoring, source-receptor relationships), aquatic effects (marine eutrophication, lake acidification, impacts on plant and fish populations), and terrestrial effects (forest decline, soil acidification, etc.).

  9. Benzoic acid derivatives from Piper species and their antiparasitic activity.

    PubMed

    Flores, Ninoska; Jiménez, Ignacio A; Giménez, Alberto; Ruiz, Grace; Gutiérrez, David; Bourdy, Genevieve; Bazzocchi, Isabel L

    2008-09-01

    Piper glabratum and P. acutifolium were analyzed for their content of main secondary constituents, affording nine new benzoic acid derivatives (1, 2, 4, 5, 7, and 10-13), in addition to four known compounds (3, 6, 8, and 9). Their structures were elucidated on the basis of spectroscopic data. Riguera ester reactions and optical rotation measurements established the new compounds as racemates. In the search for antiparasitic agents, the compounds were evaluated in vitro against the promastigote forms of Leishmania spp., Trypanosoma cruzi, and Plasmodium falciparum. Among the evaluated compounds, methyl 3,4-dihydroxy-5-(3'-methyl-2'-butenyl)benzoate (7) exhibited leishmanicidal effect (IC50 13.8-18.5 microg/mL) against the three Leishmania strains used, and methyl 3,4-dihydroxy-5-(2-hydroxy-3-methylbutenyl)benzoate (1), methyl 4-hydroxy-3-(2-hydroxy-3-methyl-3-butenyl)benzoate (3), and methyl 3,4-dihydroxy-5-(3-methyl-2-butenyl) benzoate (7) showed significant trypanocidal activity, with IC50 values of 16.4, 15.6, and 18.5 microg/mL, respectively. PMID:18712933

  10. Cetalox and analogues: synthesis via acid-mediated polyene cyclizations.

    PubMed

    Snowden, Roger L

    2008-06-01

    Using a novel, acid-mediated cyclization methodology, a direct access to Cetalox ((+/-)-1; a commercially important ambergris-type odorant) and various structurally related didehydro (i.e., 19, 26, and 30) and tetradehydro (i.e., 28 and 37/38) analogues is described. Treatment of either (E,E)-14 or (E)-15 with an excess of FSO(3)H in 2-nitropropane at -90 degrees stereospecifically afforded (+/-)-1 in 40 and 42% yield, respectively. Under similar conditions, cyclization of (E)-18 or 20 furnished 19 in 60 and 64% yield, respectively. Analogously, using an excess of ClSO(3)H in CH(2)Cl(2) at -80 degrees, 26 is formed with high stereoselectivity by cyclization of either (E)-24 or (Z)-25 (52 and 31% yield, resp.); in the same manner, 28 was prepared from 27 (22% yield). The same principle was applied to the synthesis of racemic Superambrox (30), via cyclization of 35, but only with poor selectivity (22%) and low yield (7%). Another approach via cyclization of (E)-40 under solvolysis conditions (excess TFA in CH(2)Cl(2) at -10 degrees) gave a higher yield (15%) with improved selectivity (43%). Finally, cyclization of 34 (1:1 diastereoisomer mixture) afforded 37/38 (10:1) in 27% yield. The qualitative organoleptic properties of 19, 26, 28, 30, and 37/38 (10:1) are briefly discussed. PMID:18618391

  11. Bacterial Growth, Necromass Turnover, And Endospore Abundance In The Deep Subseafloor Sediments Of The Greenland Shelf Using D:L Amino Acid Model.

    NASA Astrophysics Data System (ADS)

    Mhatre, S. S.; Braun, S.; Jaussi, M.; Røy, H.; Jørgensen, B. B.; Lomstein, B. A.

    2015-12-01

    The subsurface realm is colonized by a large number of microorganisms- about 3 × 1029. Microbial cells in these very stable and oligotrophic settings catabolize at a much slower rate than model organisms in nutrient rich cultures. The aim of this work was to use recently developed D:L-amino acid racemization model for studying the turnover times of microbial biomass and microbial necromass in a ~12,000 years old Greenland shelf marine sediment samples. Sediments were analyzed for total hydrolysable amino acids (THAA), the bacterial endospore marker dipicolinic acid (DPA), and amino acid enantiomers of aspartic acid. The percentage amino acid carbon content (%TAAC) and the percentage amino acid nitrogen content (%TAAN) were used for determining the degradation state of the organic matter. Endospores quantified using DPA quantification method were found to be as abundant as vegetative cells. The microbial necromass turnover times were thousand years, and biomass turnover times were in the range of tens to hundred years. Studies with deeper sediment cores will further improve our understanding of the energetic limits of life in the deep biosphere.

  12. Salicylic acids

    PubMed Central

    Hayat, Shamsul; Irfan, Mohd; Wani, Arif; Nasser, Alyemeni; Ahmad, Aqil

    2012-01-01

    Salicylic acid is well known phytohormone, emerging recently as a new paradigm of an array of manifestations of growth regulators. The area unleashed yet encompassed the applied agriculture sector to find the roles to strengthen the crops against plethora of abiotic and biotic stresses. The skipped part of integrated picture, however, was the evolutionary insight of salicylic acid to either allow or discard the microbial invasion depending upon various internal factors of two interactants under the prevailing external conditions. The metabolic status that allows the host invasion either as pathogenesis or symbiosis with possible intermediary stages in close systems has been tried to underpin here. PMID:22301975

  13. A comparative study of the antitussive activity of levodropropizine and dropropizine in the citric acid-induced cough model in normal subjects.

    PubMed

    Fumagalli, G; Cordaro, C I; Vanasia, M; Balzarotti, C; Camusso, L; Caiazzo, G; Maghini, L; Mazzocchi, M; Zennaro, M

    1992-01-01

    Levodropropizine is the levo-rotatory (S)-enantiomer of dropropizine, a racemic non-opiate antitussive agent which has been used clinically for many years. Compared with the racemic drug, levodropropizine exhibits in animal models similar antitussive activity but considerably lower central nervous system (CNS) depressant effects. It is also less likely to cause sedation in treated patients. Since the comparative antitussive potency of the two drugs in clinical experimental models has not been evaluated, the authors performed a randomized, double blind, cross over investigation in which the effects of single oral doses (60 and 90 mg) of levodropropizine and dropropizine were assessed by using the citric acid-induced cough model in eight normal volunteers. Stimulation tests involved inhalation of individual cumulative doses of citric acid (6.3 to 53.3 mg) which at pre-study assessment had been found to induce reproducibly at least ten coughs over a 30 sec period. Each subject was studied by repeating the citric acid stimulation test four times (0 h, 1 h, 2 h and 6 h) on each of five different days separated by intervals of at least three days. In the absence of drug administration (control session), cough response to citric inhalation was remarkably reproducible throughout the 6 h period of observation. A marked and statistically significant reduction in cough response (to about one third--one sixth of the pre-drug values) was observed 1 h after intake for both compounds. At subsequent testing 2 h and 6 h after dosing, cough response was still depressed and did not differ significantly from that observed at 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1295724

  14. Stereospecific analysis of fatty acid esters of chloropropanediol isolated from fresh goat milk.

    PubMed

    Myher, J J; Kuksis, A; Marai, L; Cerbulis, J

    1986-05-01

    The fatty acid esters of chloropropanediol isolated from goat milk fat in small quantities were subjected to a stereospecific analysis via phospholipase C and phosphocholine esters as intermediates. Synthetic rac-1-chloro-2,3-dioleoyl-propanediol was prepared by standard methods and was used as a control. The stereospecific analyses were performed following a release of the fatty acids from the primary positions of each chloropropanediol diester with pancreatic lipase. The resulting X-1-chloro-2-acylpropanediols were then converted into the corresponding phosphocholine derivatives by a stepwise reaction with phosphorus oxychloride and choline chloride. The X-1-chloro-2-acyl-3-phosphocholinepropanediols were subjected to hydrolysis with phospholipase C (C. perfringens), which hydrolyzed 50% of the phosphatide within two min and the rest of it in two hr. From previous experience with glycerol esters, it was assumed that the more rapidly hydrolyzed molecules were the sn-1-chloro-2-acyl-propanediol derivatives and the more slowly hydrolyzed ones the sn-2-acyl-3-chloropropanediol derivatives. A hydrolysis with phospholipase A2 (Crotalus adamanteus) released 50% of the total fatty acid along with the corresponding lyso compound within 10 min, after which there was no further reaction. The hydrolysis products were assayed directly by gas liquid chromatography (GLC) or were isolated by thin layer chromatography (TLC) prior to quantitation by GLC. Both naturally occurring and synthetic chloropropanediol diesters behaved similarly on stereospecific analysis and were therefore concluded to be racemic. PMID:3724368

  15. Folic acid

    MedlinePlus

    ... disease called vitiligo, and an inherited disease called Fragile-X syndrome. It is also used for reducing harmful side ... to blood clots (ischemic stroke). Inherited disease called Fragile-X syndrome.Taking folic acid by mouth does not improve ...

  16. Acid rain

    SciTech Connect

    Not Available

    1984-06-01

    An overview is presented of acid rain and the problems it causes to the environment worldwide. The acidification of lakes and streams is having a dramatic effect on aquatic life. Aluminum, present in virtually all forest soils, leaches out readily under acid conditions and interferes with the gills of all fish, some more seriously than others. There is evidence of major damage to forests in European countries. In the US, the most severe forest damage appears to be in New England, New York's Adirondacks, and the central Appalachians. This small region is part of a larger area of the Northeast and Canada that appears to have more acid rainfall than the rest of the country. It is downwind from major coal burning states, which produce about one quarter of US SO/sub 2/ emissions and one sixth of nitrogen oxide emissions. Uncertainties exist over the causes of forest damage and more research is needed before advocating expensive programs to reduce rain acidity. The President's current budget seeks an expansion of research funds from the current $30 million per year to $120 million.

  17. Formic acid

    Integrated Risk Information System (IRIS)

    Formic acid ; CASRN 64 - 18 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effect

  18. Selenious acid

    Integrated Risk Information System (IRIS)

    Selenious acid ; CASRN 7783 - 00 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  19. Benzoic acid

    Integrated Risk Information System (IRIS)

    Benzoic acid ; CASRN 65 - 85 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effec

  20. Trichloroacetic acid

    Integrated Risk Information System (IRIS)

    Trichloroacetic acid ( TCA ) ; CASRN 76 - 03 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Nonca

  1. Dichloroacetic acid

    Integrated Risk Information System (IRIS)

    Dichloroacetic acid ; CASRN 79 - 43 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogeni

  2. Acrylic acid

    Integrated Risk Information System (IRIS)

    Acrylic acid ( CASRN 79 - 10 - 7 ) Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  3. Cacodylic acid

    Integrated Risk Information System (IRIS)

    Cacodylic acid ; CASRN 75 - 60 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  4. Phosphoric acid

    Integrated Risk Information System (IRIS)

    Phosphoric acid ; CASRN 7664 - 38 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  5. Stearic Acid

    ERIC Educational Resources Information Center

    Young, Jay A.

    2004-01-01

    A chemical laboratory information profile (CLIP) is presented for the chemical, stearic acid. The profile lists the chemical's physical and harmful characteristics, exposure limits, and symptoms of major exposure, for the benefit of teachers and students, who use the chemical in the laboratory.

  6. Isolation of Lignan and Fatty Acid Derivatives from the Grains of Echinochloa utilis and Their Inhibition of Lipopolysaccharide-Induced Nitric Oxide Production in RAW 264.7 Cells.

    PubMed

    Nguyen, Duc Hung; Zhao, Bing Tian; Le, Duc Dat; Yoon, Young Ho; Ko, Jee Youn; Woo, Koan Sik; Jun, Do Youn; Kim, Young Ho; Woo, Mi Hee

    2016-01-20

    Two new fatty acid derivatives, echinochlorins A (8) and B (9) and a racemic lignan, (±)-anti-1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-acetoxypropen-1-yl]-2-methoxyphenoxy}propan-1,3-diol 3-acetate (1), were isolated from Echinochloa utilis grains, along with six known lignans (2-7) and two fatty acid derivatives (10, 11). Their structures were established by spectroscopic data analyses (IR, UV, HR-FABMS, GC-MS, and 1D and 2D NMR). The configuration of 1 was determined by Mosher's method. Compound 5 displayed potential inhibitory activity on lipopolysaccharide-induced NO production in macrophage RAW 264.7 cells with an IC50 value of 4.8 ± 0.5 μM. These isolated compounds in crude EtOH extract were also quantitated by HPLC. PMID:26725284

  7. Validation of an in vitro teratology system using chiral substances: stereoselective teratogenicity of 4-yn-valproic acid in cultured mouse embryos.

    PubMed

    Andrews, J E; Ebron-McCoy, M; Bojic, U; Nau, H; Kavlock, R J

    1995-06-01

    In vitro systems are important for toxicity testing as well as for investigating the mechanism of action of xenobiotics. The validation of such in vitro systems is often incomplete and extrapolation to the in vivo situation is equivocal. In the present study, we studied the effects of enantiomers of an analogue of the antiepileptic drug valproic acid (VPA): R(+)- and S(-)-4-yn-VPA (R- and S-2-n-propyl-4-pentynoic acid), which have previously been shown to induce selective teratogenicity in mice after in vivo administration, in mouse whole-embryo culture (WEC). Aqueous solutions of the sodium salts of the pure R- and S-enantiomers as well as R,S-4-yn-VPA (racemic mixture) or VPA itself were added to the culture medium at 0, 0.075, 0.15, 0.3, 0.6, or 1.2 mmol/liter and embryos were evaluated 24 hr later. The S-4-yn-VPA enantiomer induced clear concentration-dependent dysmorphogenesis that was evident even at the lowest concentration. The primary anomalies were neural tube defects, erratic neural seams, blisters, and rotational defects. Embryolethality was observed at 1.2 mmol/liter. The R-4-yn-VPA enantiomer was neither embryotoxic nor dysmorphogenic at any tested concentration. The lack of biological activity over 24 hr in WEC with the R-enantiomer suggests also that, as previously shown in vivo, there was no racemization of this isomer to the more active S-enantiomer. The racemic mixture of R and S isomers appeared to be slightly more embryolethal and dysmorphogenic than VPA. Overall, the potency of the S-enantiomer was approximately four times that of VPA. Therefore, the rank order of the four chemicals tested was S(-) > S(-), R(+) > VPA > R(+), which is in agreement with the effects observed in in vivo exposed mice. These data demonstrate a direct stereoselective effect of these compounds on the embryo. This is the first illustration of the stereoselectivity of a xenobiotic in the WEC in vitro test system. Pure and stable enantiomers, which induce stereoselective

  8. Corynebacterium glutamicum as a host for synthesis and export of D-Amino Acids.

    PubMed

    Stäbler, Norma; Oikawa, Tadao; Bott, Michael; Eggeling, Lothar

    2011-04-01

    A number of d-amino acids occur in nature, and there is growing interest in their function and metabolism, as well as in their production and use. Here we use the well-established l-amino-acid-producing bacterium Corynebacterium glutamicum to study whether d-amino acid synthesis is possible and whether mechanisms for the export of these amino acids exist. In contrast to Escherichia coli, C. glutamicum tolerates d-amino acids added extracellularly. Expression of argR (encoding the broad-substrate-specific racemase of Pseudomonas taetrolens) with its signal sequence deleted results in cytosolic localization of ArgR in C. glutamicum. The isolated enzyme has the highest activity with lysine (100%) but also exhibits activity with serine (2%). Upon overexpression of argR in an l-arginine, l-ornithine, or l-lysine producer, equimolar mixtures of the d- and l-enantiomers accumulated extracellularly. Unexpectedly, argR overexpression in an l-serine producer resulted in extracellular accumulation of a surplus of d-serine (81 mM d-serine and 37 mM l-serine) at intracellular concentrations of 125 mM d-serine plus 125 mM l-serine. This points to a nonlimiting ArgR activity for intracellular serine racemization and to the existence of a specific export carrier for d-serine. Export of d-lysine relies fully on the presence of lysE, encoding the exporter for l-lysine, which is apparently promiscuous with respect to the chirality of lysine. These data show that d-amino acids can also be produced with C. glutamicum and that in special cases, due to specific carriers, even a preferential extracellular accumulation of this enantiomer is possible. PMID:21257776

  9. Antioxidant properties of an endogenous thiol: Alpha-lipoic acid, useful in the prevention of cardiovascular diseases.

    PubMed

    Ghibu, Stéliana; Richard, Carole; Vergely, Catherine; Zeller, Marianne; Cottin, Yves; Rochette, Luc

    2009-11-01

    In the past few years, a growing interest has been given to the possible antioxidant functions of a natural acid, synthesized in human tissues: alpha-lipoic acid (ALA). Both the oxidized (disulfide) and reduced (dithiol: dihydrolipoic acid, DHLA) forms of ALA show antioxidant properties. ALA administered in the diet accumulates in tissues, and a substantial part is converted to DHLA via a lipoamide dehydrogenase. Commercial ALA is usually a racemic mixture of the R and S forms. Chemical studies have indicated that ALA scavenges hydroxyl radicals, hypochlorous acid, and singlet oxygen. ALA exerts antioxidant effects in biological systems not only through direct ROS quenching but also via transition metal chelation. ALA has been shown to possess a number of beneficial effects both in the prevention and treatment of diabetes in experimental conditions. ALA presents beneficial effects in the management of symptomatic diabetic neuropathy and has been used in this context in Germany for more than 30 years. In cardiovascular disease, dietary supplementation with ALA has been successfully employed in a variety of in vivo models: ischemia-reperfusion, heart failure, and hypertension. More mechanistic and human in vivo studies are needed to determine whether optimizing the dietary intake of ALA can help to decrease cardiovascular diseases. A more complete understanding of cellular biochemical events that influence oxidative damage is required to guide future therapeutic advances. PMID:19998523

  10. Gas chromatography-mass spectrometry of hexafluoroacetone derivatives: First time utilization of a gaseous phase derivatizing agent for analysis of extraterrestrial amino acids.

    PubMed

    Geffroy-Rodier, C; Buch, A; Sternberg, R; Papot, S

    2012-07-01

    Within the perspective of the current and next space missions to Mars (MSL 2011 and Exomars 2016-2018), the detection and enantioselective separation of building blocks such as the amino acids are important subjects which are becoming fundamental for the search for traces of life on the surface and subsurface of Mars. In this work, we have developed and optimized a method adapted to space experimentation to derivatize and analyze amino acids, using hexafluoroacetone as the derivatizing agent. The temperature, duration of the derivative transfer to the analyser, and chromatographic separation parameters have been optimized to meet the instrument design constraints imposed on devices for extraterrestrial experiments. The work presented in this rationale has established that hexafluoroacetone, in addition to its intrinsic qualities, such as the production of light-weight derivatives (no racemization) and great resistance to the drastic operating conditions, has indeed facilitated simple and fast derivatization that appears to be suitable for in situ analysis in space. By using hexafluoroacetone as the derivatizing agent, we successfully identified, 21 amino acids including 12 of the 20 proteinic amino acids without stirring or extraction steps. Ten of these derivatized amino acids were enantioselectively separated. The precision and accuracy measurements for the D/L ratio showed that the proposed method was also suitable for the determination of both enantioselective forms of most of the tested amino acids. The limits of detection obtained were lower than the ppb level of organic molecules detected in Martian meteorites. PMID:22633064

  11. Non-ionic surfactant modified ligand exchange chromatography using copper (II) complex of N,N-dimethyl-L-phenylalanine as the chiral additive for enantioselective amino acids separation.

    PubMed

    Dimitrova, Pepa; Bart, Hans-Jörg

    2010-03-17

    The influence of non-ionic surfactants on the selectivity and retention in the ligand exchange chromatography for the enantioselective separation of racemic mixtures of the amino acids dl-methionine, dl-leucine, dl-valine and dl-tyrosine applying chiral mobile phases was investigated, whereas five different surfactants were tested as modifiers. The experiments were carried out using a commercially available non-chiral RP-C8 column and the copper (II) complex of N,N-dimethyl-l-phenylalanine as the chiral additive. Varying the surfactant concentrations the retention factors and the selectivity could be controlled and in general no negative influence on the separation (due to surfactant adsorption on the non-chiral stationary phase) occurred. Changing the temperature the van't Hoff plots were obtained and the thermodynamic parameters calculated. Temperature had influence on the selectivity for each surfactant and lowered the retention times as expected. PMID:20172105

  12. Analytical Enantioseparation of β-Substituted-2-Phenylpropionic Acids by High-Performance Liquid Chromatography with Hydroxypropyl-β-Cyclodextrin as Chiral Mobile Phase Additive.

    PubMed

    Tong, Shengqiang; Zhang, Hu; Yan, Jizhong

    2016-04-01

    Analytical enantioseparation of five β-substituted-2-phenylpropionic acids by high-performance liquid chromatography with hydroxypropyl-β-cyclodextrin (HP-β-CD) as chiral mobile phase additive was established in this paper, and chromatographic retention mechanism was studied. The effects of various factors such as the organic modifier, different ODS C18 columns and concentration of HP-β-CD were investigated. The chiral mobile phase was composed of methanol or acetonitrile and 0.5% triethylamine acetate buffer at pH 3.0 added with 25 mmol L(-1) of HP-β-CD, and baseline separations could be reached for all racemates. As for chromatographic retention mechanism, it was found that there was a negative correlation between the concentration of HP-β-CD in mobile phase and the retention factor under constant pH value and column temperature. PMID:26755500

  13. Hydroxycarboxylic acids and salts

    DOEpatents

    Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N

    2015-02-24

    Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.

  14. AAR in concrete of Asejire spillway (OYO state - Nigeria)

    SciTech Connect

    Lamaudiere, J.P.; Spaeti, F.

    1995-12-31

    The Asejire dam at Ibadan, Nigeria was constructed in the late sixties for the purpose of providing water for the city of Ibadan (presently about 4,5 million inhabitants). It is located on the Oshun river approximately fifteen miles from the city. In 1982 cracks were observed on the wing walls and although these continued to develop, no attempt was made at that time to investigate their causes and no repair was carried out. In 1989 the SGI ENGINEERING Group of Geneva, Switzerland was appointed as the consultant for the complete refurbishment of the Asejire water scheme. The consortium Degremont-Poat-Clemessy was awarded the contract for the project. The African Development Bank and the Nigerian Government have provided the loan to finance the project.

  15. F/A-18 Automated Aerial Refueling (AAR) Phase 1

    NASA Video Gallery

    Engineers at NASA's Dryden Flight Research Center are evaluating the capability of an F/A-18A aircraft as an in-flight refueling tanker to develop analytical models for an automated aerial refuelin...

  16. Amino acid preservation in saline halite core samples: Analogs for Martian dry evaporitic regions

    NASA Astrophysics Data System (ADS)

    Bada, J.; Aubrey, A.; Lowenstein, T.; Timofeeff, M.

    2008-12-01

    Recent data returned from several Mars spacecraft show substantial evidence for mineral precipitation from bodies of liquid water. Evaporitic minerals such as gypsum, kieserite and poly-hydrated magnesium sulfates have been detected remotely by orbiting spacecraft [1], jarosite has been detected in situ by the MER Opportunity [2], and chlorides are highly abundant upon the surface of Mars [3], often in correlation with siliclastic deposits [4]. Terrestrial environments can provide analogs for these systems identified on the Martian surface, and in-depth characterization of the terrestrial systems can provide valuable insights into processes that may have occurred on Mars during the late Noachian/early Hesperian. This is especially true in ancient playa or evaporative basin environments where deep core sampling offers a method of observing the geochemical diagenetic changes with time within a constrained environment. Deep coring can provide samples upwards of 200 ka within hundreds of meters of core [5]. The analysis of these sections can allow for the determination of preservation of various biosignatures from extinct microbial communities as well as their in situ diagenetic rates. Amino acids are powerful biomarkers that can be used to estimate biomass [6] and determine ages of extinct microbial communities [7]. Preliminary data for a core sample collected from Saline Valley, CA, shows the effect of time on amino acid biosignatures. The core has been dated by U-series: 35 feet, 20.9 ± 1.1 ka; 127 feet, 61.1 ±2.8 ka; 204 feet, 73.9 ±4.8 ka; and 310 feet, 150.3 ± 7.8 ka. The abundance of amino acids is observed to decrease drastically over the first 20 ka and then stabilize, although the overall composition changes. Acidic amino acids along with alanine and valine are the dominant amino acids. The enantiomeric (D/L) ratios generally increase with age because of in situ racemization, although the enantiomeric ratios for alanine and glutamic acid show a decrease

  17. Methylmalonic acid blood test

    MedlinePlus

    ... acid is a substance produced when proteins, called amino acids, in the body break down. The health care ... Cederbaum S, Berry GT. Inborn errors of carbohydrate, ammonia, amino acid, and organic acid metabolism. In: Gleason CA, Devaskar ...

  18. Folic acid - test

    MedlinePlus

    Folic acid is a type of B vitamin. This article discusses the test to measure the amount of folic acid in the blood. ... that may interfere with test results, including folic acid supplements. Drugs that can decrease folic acid measurements ...

  19. Uric acid urine test

    MedlinePlus

    The uric acid urine test measures the level of uric acid in urine. Uric acid level can also be checked using a blood ... help determine the cause of a high uric acid level in the blood. It may also be ...

  20. Methylmalonic acid blood test

    MedlinePlus

    The methylmalonic acid blood test measures the amount of methylmalonic acid in the blood. ... Methylmalonic acid is a substance produced when proteins, called amino acids, in the body break down. The health care ...

  1. Folic Acid and Pregnancy

    MedlinePlus

    ... 5 Things to Know About Zika & Pregnancy Folic Acid and Pregnancy KidsHealth > For Parents > Folic Acid and ... before conception and during early pregnancy . About Folic Acid Folic acid, sometimes called folate, is a B ...

  2. Fermentative production of lactic acid from biomass: an overview on process developments and future perspectives.

    PubMed

    John, Rojan P; Nampoothiri, K Madhavan; Pandey, Ashok

    2007-03-01

    The concept of utilizing excess biomass or wastes from agricultural and agro-industrial residues to produce energy, feeds or foods, and other useful products is not necessarily new. Recently, fermentation of biomass has gained considerable attention due to the forthcoming scarcity of fossil fuels and also due to the necessity of increasing world food and feed supplies. A cost-effective viable process for lactic acid production has to be developed for which several attempts have been initiated. Fermentation techniques result in the production of either D: (-) or L: (+) lactic acid, or a racemic mixture of both, depending on the type of organism used. The interest in the fermentative production of lactic acid has increased due to the prospects of environmental friendliness and of using renewable resources instead of petrochemicals. Amylolytic bacteria Lactobacillus amylovorus ATCC 33622 is reported to have the efficiency of full conversion of liquefied cornstarch to lactic acid with a productivity of 20 g l(-1) h(-1). A maximum of 35 g l(-1) h(-1) was reported using a high cell density of L. helveticus (27 g l(-1)) with a complete conversion of 55- to 60-g l(-1) lactose present in whey. Simultaneous saccharification and fermentation is proved to be best in the sense of high substrate concentration in lower reactor volume and low fermentation cost. In this review, a survey has been made to see how effectively the fermentation technology explored and exploited the cheaply available source materials for value addition with special emphasis on lactic acid production. PMID:17225102

  3. Synthesis and use of stereospecifically deuterated analogues of palmitic Acid to investigate the stereochemical course of the delta11 desaturase of the processionary moth.

    PubMed

    Abad, José-Luis; Villorbina, Gemma; Fabriàs, Gemma; Camps, Francisco

    2004-10-15

    Thaumetopoea pityocampa pheromone glands contain desaturases that, after several sequential reactions from palmitic acid, catalyze the formation of a unique enyne fatty acid, which is the immediate sex pheromone precursor. In this article, we describe the synthesis of different stereospecifically deuterium-labeled and isotopically tagged palmitic acid probes needed to decipher the stereochemical course of the T. pityocampa Delta(11) desaturase. The synthesis of probes has been carried out by a chemoenzymatic route, in which the key step is the kinetic lipase-catalyzed resolution of racemic mixtures of secondary propargyl alcohols. The presence of the acetylenic bond simplifies the absolute configuration determination of the resolved alcohols. Moreover, it allows the introduction of the isotopic tag by deuteration. By use of the probes thus prepared, experimental evidence is presented that the Delta(11) desaturase of T. pityocampa transforms palmitic acid into (Z)-11-hexadecenoic acid by removal of the pro-(R)-hydrogen atoms from both C11 and C12. PMID:15471459

  4. Understanding Acid Rain

    ERIC Educational Resources Information Center

    Damonte, Kathleen

    2004-01-01

    The term acid rain describes rain, snow, or fog that is more acidic than normal precipitation. To understand what acid rain is, it is first necessary to know what an acid is. Acids can be defined as substances that produce hydrogen ions (H+), when dissolved in water. Scientists indicate how acidic a substance is by a set of numbers called the pH…

  5. New bioactive fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compounds, 7,10-dihydroxy-8(E)-octad...

  6. New Bioactive Fatty Acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to new compounds, 7,10-dihydroxy-8(E)-octadecen...

  7. An evaluation of Mesodon and other larger terrestrial gastropod shells for dating late Holocene and historic alluvium in the Midwestern USA

    NASA Astrophysics Data System (ADS)

    Rakovan, Monica T.; Rech, Jason A.; Pigati, Jeffrey S.; Nekola, Jeffrey C.; Wiles, Gregory C.

    2013-07-01

    Understanding the history of stream erosion and changes in channel morphology is important for managing and restoring unstable streams. One of the significant challenges in this type of research is establishing accurate dating of late Holocene and historic alluvium. Here we evaluate the potential of using 14C dating and amino acid racemization (AAR) to date large terrestrial gastropod shells that are often preserved within alluvial sediments. Many terrestrial gastropods incorporate old carbon from limestone or other carbonate rocks into their shells and therefore are unsuitable for radiocarbon dating. Recent studies, however, have shown that some taxa avoid this 'limestone problem' and can yield reliable 14C ages. In this study, we measured the 14C activity of specimens for the genera Mesodon, Ventridens, and Allogona collected live and from alluvial sequences dated independently by dendrochronology, 14C dating of wood, and/or 137Cs analyses. Mesodon zaletus contained old carbon in similar concentrations (up to ~ 30%) found in previous studies of other large taxa and should be avoided for 14C dating when possible. In contrast, shells of Ventridens ligera and Allogona profunda showed minimal limestone effects and therefore may be suitable for dating late Holocene alluvium. These results highlight the importance of taxonomic identification of gastropod taxa prior to their use for 14C dating and demonstrate that shell fragments that are not identifiable should be avoided. We also measured d/l ratios (n = 17) of aspartic and glutamic acid from eight different taxa of terrestrial gastropods recovered from four late Holocene and historic stratigraphic sequences. Average d/l ratios of aspartic and glutamic acid from historic sediments < 300 years old are lower in shells from younger stratigraphic units, indicating that AAR can be used to differentiate between multiple historic stratigraphic units.

  8. An evaluation of Mesodon and other larger terrestrial gastropod shells for dating late Holocene and historic alluvium in the Midwestern USA

    USGS Publications Warehouse

    Rakovan, Monica T.; Rech, Jason A.; Pigati, Jeffery S.; Nekola, Jeffery C.; Wiles, Gregory C.

    2013-01-01

    Understanding the history of stream erosion and changes in channel morphology is important for managing and restoring unstable streams. One of the significant challenges in this type of research is establishing accurate dating of late Holocene and historic alluvium. Here we evaluate the potential of using 14C dating and amino acid racemization (AAR) to date large terrestrial gastropod shells that are often preserved within alluvial sediments. Many terrestrial gastropods incorporate old carbon from limestone or other carbonate rocks into their shells and therefore are unsuitable for radiocarbon dating. Recent studies, however, have shown that some taxa avoid this ‘limestone problem’ and can yield reliable 14C ages. In this study, we measured the 14C activity of specimens for the genera Mesodon, Ventridens, and Allogona collected live and from alluvial sequences dated independently by dendrochronology, 14C dating of wood, and/or 137Cs analyses. Mesodon zaletus contained old carbon in similar concentrations (up to ~ 30%) found in previous studies of other large taxa and should be avoided for 14C dating when possible. In contrast, shells of Ventridens ligera and Allogona profunda showed minimal limestone effects and therefore may be suitable for dating late Holocene alluvium. These results highlight the importance of taxonomic identification of gastropod taxa prior to their use for 14C dating and demonstrate that shell fragments that are not identifiable should be avoided. We also measured d/l ratios (n = 17) of aspartic and glutamic acid from eight different taxa of terrestrial gastropods recovered from four late Holocene and historic stratigraphic sequences. Average d/l ratios of aspartic and glutamic acid from historic sediments < 300 years old are lower in shells from younger stratigraphic units, indicating that AAR can be used to differentiate between multiple historic stratigraphic units.

  9. Recombinant polycistronic structure of hydantoinase process genes in Escherichia coli for the production of optically pure D-amino acids.

    PubMed

    Martínez-Gómez, Ana Isabel; Martínez-Rodríguez, Sergio; Clemente-Jiménez, Josefa María; Pozo-Dengra, Joaquín; Rodríguez-Vico, Felipe; Las Heras-Vázquez, Francisco Javier

    2007-03-01

    Two recombinant reaction systems for the production of optically pure D-amino acids from different D,L-5-monosubstituted hydantoins were constructed. Each system contained three enzymes, two of which were D-hydantoinase and D-carbamoylase from Agrobacterium tumefaciens BQL9. The third enzyme was hydantoin racemase 1 for the first system and hydantoin racemase 2 for the second system, both from A. tumefaciens C58. Each system was formed by using a recombinant Escherichia coli strain with one plasmid harboring three genes coexpressed with one promoter in a polycistronic structure. The D-carbamoylase gene was cloned closest to the promoter in order to obtain the highest level of synthesis of the enzyme, thus avoiding intermediate accumulation, which decreases the reaction rate. Both systems were able to produce 100% conversion and 100% optically pure D-methionine, D-leucine, D-norleucine, D-norvaline, D-aminobutyric acid, D-valine, D-phenylalanine, D-tyrosine, and D-tryptophan from the corresponding hydantoin racemic mixture. For the production of almost all D-amino acids studied in this work, system 1 hydrolyzed the 5-monosubstituted hydantoins faster than system 2. PMID:17220246

  10. Multidimensional separation of chiral amino acid mixtures in a multilayered three-dimensional hybrid microfluidic/nanofluidic device.

    PubMed

    Kim, Bo Young; Yang, Jing; Gong, Maojun; Flachsbart, Bruce R; Shannon, Mark A; Bohn, Paul W; Sweedler, Jonathan V

    2009-04-01

    Microscale total analysis systems (microTAS) allow high-throughput analyses by integrating multiple processes, parallelization, and automation. Here we combine unit operations of microTAS to create a device that can perform multidimensional separations using a three-dimensional hybrid microfluidic/nanofluidic device composed of alternating layers of patterned poly(methyl methacrylate) and nanocapillary array membranes constructed from nuclear track-etched polycarbonate. Two consecutive electrophoretic separations are performed, the first being an achiral separation followed by a chiral separation of a selected analyte band. Separation conditions are optimized for a racemic mixture of fluorescein-isothiocyanate-labeled amino acids, serine and aspartic acid, chosen because there are endogenous D-forms of these amino acids in animals. The chiral separation is implemented using micellar electrokinetic chromatography using beta-cyclodextrin as the chiral selector and sodium taurocholate as the micelle-forming agent. Analyte separation is monitored by dual-beam laser-induced fluorescence detection. After separation in the first electrophoretic channel, the preselected analyte is sampled by the second-stage separation using an automated collection sequence with a zero-crossing algorithm. The controlled fluidic environment inherent to the three-dimensional architecture enables a series of separations in varying fluidic environments and allows sample stacking via different background electrolyte pH conditions. The ability to interface sequential separations, selected analyte capture, and other fluidic manipulations in the third dimension significantly improves the functionality of multilayer microfluidic devices. PMID:19271741

  11. Advanced dress-up chiral columns: New removable chiral stationary phases for enantioseparation of chiral carboxylic acids.

    PubMed

    Todoroki, Kenichiro; Ishii, Yasuhiro; Ide, Takafumi; Min, Jun Zhe; Inoue, Koichi; Huang, Xin; Zhang, Wei; Hamashima, Yoshitaka; Toyo'oka, Toshimasa

    2015-07-01

    This paper describes the preparation of new dress-up columns featuring reproducibly removable and replaceable chiral stationary phases. After synthesizing perfluroalkylated quinine and quinidine derivatives as chiral stationary phase compounds (F-CSPs), we adsorbed them reversibly onto a fluorous LC column through pumping of their solutions. Using this dress-up chiral column and fluorophobic elution of aqueous ammonium formate/MeOH mixtures, we could enantioseparate four racemic N-acetyl amino acids, dichlorprop, and sixteen fluorescent 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC)-derivatized amino acids. Dressing and undressing of the coated F-CSPs could be controlled by varying the fluorophilicity and fluorophobicity of the eluent. The relative standard deviations of the retention times, the retention factors, the number of theoretical plates, the enantioseparation factors, and the resolutions of each of four preparations of such dress-up columns were all less than or equal to 5.26% (from 20 repeated analyses); the reproducibilities from four different preparations were all less than or equal to 10.6%. These columns also facilitated highly sensitive and selective analyses of AQC-amino acids when detected using LC-MS/MS. PMID:26043097

  12. Degradation and enantiomeric fractionation of mecoprop in soil previously exposed to phenoxy acid herbicides - New insights for bioremediation.

    PubMed

    Frková, Zuzana; Johansen, Anders; de Jonge, Lis Wollesen; Olsen, Preben; Gosewinkel, Ulrich; Bester, Kai

    2016-11-01

    Phenoxy acid-contaminated subsoils are common as a result of irregular disposal of residues and production wastes in the past. For enhancing in situ biodegradation at reducing conditions, biostimulation may be an effective option. Some phenoxy acids were marketed in racemic mixtures, and biodegradation rates may differ between enantiomers. Therefore, enantio-preferred degradation of mecoprop (MCPP) in soil was measured to get in-depth information on whether amendment with glucose (BOD equivalents as substrate for microbial growth) and nitrate (redox equivalents for oxidation) can stimulate bioremediation. The degradation processes were studied in soil sampled at different depths (3, 4.5 and 6m) at a Danish urban site with a history of phenoxy acid contamination. We observed preferential degradation of the R-enantiomer only under aerobic conditions in the soil samples from 3- and 6-m depth at environmentally relevant (nM) MCPP concentrations: enantiomer fraction (EF)<0.5. On the other hand, we observed preferential degradation of the S-enantiomer in all samples and treatments at elevated (μM) MCPP concentrations: EF>0.5. Three different microbial communities were discriminated by enantioselective degradation of MCPP: 1) aerobic microorganisms with little enantioselectivity, 2) aerobic microorganisms with R-selectivity and 3) anaerobic denitrifying organisms with S-selectivity. Glucose-amendment did not enhance MCPP degradation, while nitrate amendment enhanced the degradation of high concentrations of the herbicide. PMID:27432728

  13. Remote Enantioselection Transmitted by an Achiral Peptide Nucleic Acid Backbone

    NASA Technical Reports Server (NTRS)

    Kozlov, Igor A.; Orgel, Leslie E.; Nielsen, Peter E.

    2000-01-01

    short homochiral segment of DNA into a PNA helix could have guaranteed that the next short segment of DNA to be incorporated would have the same handedness as the first. Once two segments of the same handedness were present, the probability that a third segment would have the same handedness would increase, and so on. Evolution could then slowly dilute out the PNA part. This scenario would ultimately allow the formation of a chiral oligonucleotide by processes that are largely resistant to enantiomeric crossinhibition. It is important to note that the ligation of homochiral dinucleotides on a nucleic acid template would probably be at least as enantiospecific as the reaction that we have studied. The disadvantage of using chiral monomers as components of a replicating system arises from the difficulty of generating a first long homochiral template from a racemic mixture of monomers, although results of experiments designed to overcome this difficulty by employing homochiral tetramers have been reported.l l The probability of obtaining a homochiral n-mer from achiral substrates is approximately 1P-I if the nontemplate-directed extension of the primer is not enantioselective. Hence, it would be very hard to get started with a homochiral 40-mer, for example. No such difficulty exists in a scenario that originates with an achiral genetic material and in which the incorporation of very few chiral monomers in this achiral background gradually progresses towards homochirality. It seems possible that some PNA sequences could act as catalysts, analogous to ribozymes, even though PNA lacks clear metal binding sites. Although such catalysts could not be enantioselective, the incorporation of as few as two chiral nucleotides could then impose chiral specificity on the system. Furthermore, such patch chimeras could help to bridge the gap in catalytic potential between PNA and RNA, while guaranteeing enantioselectivity.

  14. Synthesis of Hydroxylated Bicyclic Amino Acids from l-Tyrosine: Octahydro-1H-indole Carboxylates

    PubMed Central

    Pierce, Joshua G.; Kasi, Dhanalakshmi; Fushimi, Makoto; Cuzzupe, Anthony; Wipf, Peter

    2009-01-01

    A stereoselective approach to polyhydroxylated l-Choi derivatives has been developed. The oxidative cyclization of l-tyrosine was optimized to avoid partial racemization and to allow a more efficient scale-up. PMID:18767800

  15. The effect of ionizing radiation on amino acids and bacterial spores in different geo- and cosmochemical environments

    NASA Astrophysics Data System (ADS)

    Kminek, Gerhard

    In this thesis I have investigated the impact of ionizing radiation from the environment on the stability of bacterial spores and amino acids. I measured the radiolysis constant of amino acids and the inactivation constant of bacterial spores. To put these results in the context of a natural setting, I have selected four different cases and calculated the radiation environment for meteorites, the Martian subsurface, terrestrial halite fluid inclusions, and fossil bones. Bacterial spores exhibit a remarkable resistance to adverse environments and are the best example for the long-term survival of life forms. On a molecular level, amino acids are of particular interest because of their importance in biochemistry and their stability in the environment. The significance of amino acids, however, goes back to a time before life existed. The exogenous delivery of amino acids by meteorites might have been essential to provide the required supply of organic molecules for the origin of life on the Earth. There is one common threat, however, to the preservation of amino acids and bacterial spores in all known terrestrial and extraterrestrial environments: ionizing radiation. Amino acids in meteorites are exposed to radiation from internal radioactivity and space radiation. I show that this radiation decomposes substantial amounts of amino acids over time, indicating a higher exogenous delivery of amino acids to the early Earth. The total radiodecomposition since the synthesis of amino acids is between 23 and 68%. Radiodecomposition induces a certain fractionation in favor of smaller amino acids. Fossil bones show a post-mortem uranium uptake. My results suggest a substantial radiodecomposition of amino acids on a 10 million year time scale. Age determination based on racemization of amino acids will be affected in fossil bones that are older than 1--30 million years. My results on the stability of bacterial spores in halite fluid inclusions and on Mars suggest that radiation

  16. 4-(3-Methoxyphenyl)-2,6-dimethylcyclohex-3-enecarboxylic acid

    SciTech Connect

    Xie, Songwen; Nusbaum, Dannette A.; Stein, Holly J.; Pink, Maren

    2012-03-15

    The racemic title compound, C{sub 16}H{sub 20}O{sub 3}, was synthesized to study the hydrogen-bonding interaction of the two enantiomers in the solid state. In the crystal structure, R and S pairs of the racemate are linked by pairs of intermolecular O-H...O hydrogen bonds, producing centrosymmetric R{sub 2}{sup 2}(8) rings.

  17. Bioactive Fatty Acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxygenated fatty acids are useful as specialty chemicals, plasticizers, and biomedicals. Microbial enzymes convert fatty acids to mono-, di-, and trihydroxy fatty acid products. Among them, Bacillus megaterium ALA2 converted n-6 and n-3 PUFAs to many new oxygenated fatty acids. Linoleic acid was ...

  18. Stereochemical features of the hydrolysis of 9,10-epoxystearic acid catalysed by plant and mammalian epoxide hydrolases.

    PubMed Central

    Summerer, Stephan; Hanano, Abdulsamie; Utsumi, Shigeru; Arand, Michael; Schuber, Francis; Blée, Elizabeth

    2002-01-01

    cis-9,10-epoxystearic acid was used as a tool to probe the active sites of epoxide hydrolases (EHs) of mammalian and plant origin. We have compared the stereochemical features of the hydrolysis of this substrate catalysed by soluble and membrane-bound rat liver EHs, by soluble EH (purified to apparent homogeneity) obtained from maize seedlings or celeriac roots, and by recombinant soybean EH expressed in yeast. Plant EHs were found to differ in their enantioselectivity, i.e. their ability to discriminate between the two enantiomers of 9,10-epoxystearic acid. For example, while the maize enzyme hydrated both enantiomers at the same rate, the EH from soybean exhibited very high enantioselectivity in favour of 9R,10S-epoxystearic acid. This latter enzyme also exhibited a strict stereoselectivity, i.e. it hydrolysed the racemic substrate with a very high enantioconvergence, yielding a single chiral diol product, threo-9R,10R-dihydroxystearic acid. Soybean EH shared these distinctive stereochemical features with the membrane-bound rat liver EH. The stereochemical outcome of these enzymes probably results from a stereoselective attack by the nucleophilic residue on the oxirane ring carbon having the (S)-configuration, leading to the presumed (in plant EH) covalent acyl-enzyme intermediate. In sharp contrast, the reactions catalysed by cytosolic rat liver EH exhibited a complete absence of enantioselectivity and enantioconvergence; this latter effect might be ascribed to a regioselective formation of the acyl-enzyme intermediate involving C-10 of 9,10-epoxystearic acid, independent of its configuration. Thus, compared with soybean EH, the active site of rat liver soluble EH displays a very distinct means of anchoring the oxirane ring of the fatty acid epoxides, and therefore appears to be a poor model for mapping the catalytic domain of plant EHs. PMID:12020347

  19. Stereochemical features of the hydrolysis of 9,10-epoxystearic acid catalysed by plant and mammalian epoxide hydrolases.

    PubMed

    Summerer, Stephan; Hanano, Abdulsamie; Utsumi, Shigeru; Arand, Michael; Schuber, Francis; Blée, Elizabeth

    2002-09-01

    cis-9,10-epoxystearic acid was used as a tool to probe the active sites of epoxide hydrolases (EHs) of mammalian and plant origin. We have compared the stereochemical features of the hydrolysis of this substrate catalysed by soluble and membrane-bound rat liver EHs, by soluble EH (purified to apparent homogeneity) obtained from maize seedlings or celeriac roots, and by recombinant soybean EH expressed in yeast. Plant EHs were found to differ in their enantioselectivity, i.e. their ability to discriminate between the two enantiomers of 9,10-epoxystearic acid. For example, while the maize enzyme hydrated both enantiomers at the same rate, the EH from soybean exhibited very high enantioselectivity in favour of 9R,10S-epoxystearic acid. This latter enzyme also exhibited a strict stereoselectivity, i.e. it hydrolysed the racemic substrate with a very high enantioconvergence, yielding a single chiral diol product, threo-9R,10R-dihydroxystearic acid. Soybean EH shared these distinctive stereochemical features with the membrane-bound rat liver EH. The stereochemical outcome of these enzymes probably results from a stereoselective attack by the nucleophilic residue on the oxirane ring carbon having the (S)-configuration, leading to the presumed (in plant EH) covalent acyl-enzyme intermediate. In sharp contrast, the reactions catalysed by cytosolic rat liver EH exhibited a complete absence of enantioselectivity and enantioconvergence; this latter effect might be ascribed to a regioselective formation of the acyl-enzyme intermediate involving C-10 of 9,10-epoxystearic acid, independent of its configuration. Thus, compared with soybean EH, the active site of rat liver soluble EH displays a very distinct means of anchoring the oxirane ring of the fatty acid epoxides, and therefore appears to be a poor model for mapping the catalytic domain of plant EHs. PMID:12020347

  20. Molecular aggregation in selected crystalline 1:1 complexes of hydrophobic D- and L-amino acids. IV. The L-phenylalanine series.

    PubMed

    Görbitz, Carl Henrik; Rissanen, Kari; Valkonen, Arto; Husabø, Asmund

    2009-06-01

    The amino acid L-phenylalanine has been cocrystallized with D-2-aminobutyric acid, C(9)H(11)NO(2).C(4)H(9)NO(2), D-norvaline, C(9)H(11)NO(2).C(5)H(11)NO(2), and D-methionine, C(9)H(11)NO(2).C(5)H(11)NO(2)S, with linear side chains, as well as with D-leucine, C(9)H(11)NO(2).C(6)H(13)NO(2), D-isoleucine, C(9)H(11)NO(2).C(6)H(13)NO(2), and D-allo-isoleucine, C(9)H(11)NO(2).C(6)H(13)NO(2), with branched side chains. The structures of these 1:1 complexes fall into two classes based on the observed hydrogen-bonding pattern. From a comparison with other L:D complexes involving hydrophobic amino acids and regular racemates, it is shown that the structure-directing properties of phenylalanine closely parallel those of valine and isoleucine but not those of leucine, which shares side-chain branching at C(gamma) with phenylalanine and is normally considered to be the most closely related non-aromatic amino acid. PMID:19498234

  1. Organometallic Enantiomeric Scaffolding: General Access to 2-Substituted Oxa- and Azabicyclo[3.2.1]octenes via a Brønsted Acid-catalyzed [5+2] Cycloaddition Reaction

    PubMed Central

    Garnier, Ethel C.; Liebeskind, Lanny S.

    2009-01-01

    6-Substituted TpMo(CO)2(η-2,3,4-pyranyl)- and TpMo(CO)2(η-2,3,4-pyridinyl) scaffolds (Tp = hydridotrispyrazolylborato) function as reaction partners in an efficient regio- and stereocontrolled synthesis of functionalized oxa- and azabicyclo[3.2.1]octenes through a novel Brønsted acid-catalyzed [5+2] cycloaddition reaction. Excellent exo-selectivities are obtained and the reaction gives products with complete retention of enantiomeric purity when carried out with chiral, non-racemic scaffolds. The substituent at C-6 of the η3-coordinated heterocyclic scaffold not only influences [5+2] reactivity but also plays a critical role in the demetalation step directing the reaction to only one of two possible products. PMID:18479131

  2. Crystal structure of 1,3-dihy-droxy-2-(hy-droxy-meth-yl)propan-2-aminium 2-(4-iso-butyl-phen-yl)propano-ate: a simple organic salt of racemic ibuprofen.

    PubMed

    Lou, Benyong

    2015-08-01

    In the title organic salt of ibuprofen with trometamol, C4H12NO3 (+)·C13H17O2 (-), the carb-oxy-lic acid group of ibuprofen has transferred its proton to the amino N atom of trometamol. In the crystal, the trometamol cations are linked via N-H⋯O hydrogen bonds, forming chains along [001]. To these chains are attached the ibuprofen anions via O-H⋯O and N-H⋯O hydrogen bonds. The chains are linked via further N-H⋯O and O-H⋯O hydrogen bonds, forming sheets parallel to (100). Two C atoms of the propano-ate substituent in the ibuprofen anion are disordered over two sets of sites and were refined with a fixed occupancy ratio of 0.7:0.3. PMID:26396756

  3. Uric acid test (image)

    MedlinePlus

    Uric acid urine test is performed to check for the amount of uric acid in urine. Urine is collected over a 24 ... testing. The most common reason for measuring uric acid levels is in the diagnosis or treatment of ...

  4. Amino Acid Metabolism Disorders

    MedlinePlus

    ... defects & other health conditions > Amino acid metabolism disorders Amino acid metabolism disorders E-mail to a friend Please ... baby’s newborn screening may include testing for certain amino acid metabolism disorders. These are rare health conditions that ...

  5. Plasma amino acids

    MedlinePlus

    Amino acids blood test ... types of methods used to determine the individual amino acid levels in the blood. ... test is done to measure the level of amino acids in the blood. An increased level of a ...

  6. Stomach acid test

    MedlinePlus

    Gastric acid secretion test ... of the cells in the stomach to release acid. The stomach contents are then removed and analyzed. ... 3.5). These numbers are converted to actual acid production in units of milliequivalents per hour in ...

  7. Azelaic Acid Topical

    MedlinePlus

    Azelaic acid gel is used to clear the bumps, lesions, and swelling caused by rosacea (a skin disease that ... redness, flushing, and pimples on the face). Azelaic acid cream is used to treat acne. Azelaic acid ...

  8. Facts about Folic Acid

    MedlinePlus

    ... Information For... Media Policy Makers Facts About Folic Acid Language: English Español (Spanish) Recommend on Facebook Tweet ... of the baby's brain and spine. About folic acid Folic acid is a B vitamin. Our bodies ...

  9. Acid Lipase Disease

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Acid Lipase Disease Information Page Synonym(s): Cholesterol Ester Storage ... Trials Related NINDS Publications and Information What is Acid Lipase Disease ? Acid lipase disease or deficiency occurs ...

  10. Evaluation of a series of prolylamidepyridines as the chiral derivatization reagents for enantioseparation of carboxylic acids by LC-ESI-MS/MS and the application to human saliva.

    PubMed

    Kuwabara, Tomohiro; Takayama, Takahiro; Todoroki, Kenichiro; Inoue, Koichi; Min, Jun Zhe; Toyo'oka, Toshimasa

    2014-04-01

    Mass spectrometry has become a popular analytical tool because of its high sensitivity and specificity. The use of a chiral derivatization reagent for the mass spectrometry (MS) detection seems to be efficient for the enantiomeric separation of racemates. However, the number of chiral reagents for the liquid chromatography (LC)-MS/MS analysis is very limited. According to these observations, we are currently in the process of developing novel labeling reagents for chiral molecules in MS/MS analysis. The derivatization reagent that is effective for enhancing not only the electrospray ionization-MS/MS sensitivity but also the reversed-phase LC resolution of carboxylic acid enantiomers should have a highly proton-affinitive moiety and an asymmetric structure near the reactive functional group. Furthermore, the resulting derivative has to provide a characteristic product ion suitable for the selected reaction monitoring. Based upon these considerations, a series of prolylamidepyridines ((S)-N-pyrrolidine-2-carboxylic acid N-(pyridine-2-yl)amide (PCP2), (S)-N-pyrrolidine-2-carboxylic acid N-(pyridine-3-yl)amide, and (S)-N-pyrrolidine-2-carboxylic acid N-(pyridine-4-yl)amide) was synthesized as ideal labeling reagents for the enantioseparation of chiral carboxylic acids and evaluated in terms of separation efficiency and detection sensitivity by ultra-performance LC (UPLC)-MS/MS. Among the synthesized reagents, PCP2 was the most efficient chiral derivatization reagent for the enantioseparation of carboxylic acid. The Rs values and the detection limits of the derivatives of non-steroidal anti-inflammatory drugs, which were selected as the representative carboxylic acids, were in the range of 2.52-6.07 and 49-260 amol, respectively. The sensitive detection of biological carboxylic acids (detection limits, 32-520 amol) was also carried out by the proposed method using PCP2 and UPLC-MS/MS. The PCP2 was applied to the determination of carboxylic acids in human saliva. Several

  11. Folic acid - test

    MedlinePlus

    ... folic acid measurements include: Alcohol Aminosalicylic acid Birth control pills Estrogens Tetracyclines Ampicillin Chloramphenicol Erythromycin Methotrexate Penicillin Aminopterin Phenobarbital Phenytoin Drugs to treat malaria

  12. Oxalic acid poisoning

    MedlinePlus

    Symptoms of oxalic acid poisoning include: Abdominal pain Burns and blisters where the acid contacted the skin Collapse Convulsions Mouth pain Shock Throat pain Tremors (unintentional trembling) Vomiting

  13. Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes

    NASA Astrophysics Data System (ADS)

    Xue, Shan-Shan; Zhao, Meng; Ke, Zhuo-Feng; Cheng, Bei-Chen; Su, Hua; Cao, Qian; Cao, Zhen-Kun; Wang, Jun; Ji, Liang-Nian; Mao, Zong-Wan

    2016-02-01

    It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1-S3) at neutral pH indicated that the “back-to-back” bisCD complex CuL1 favoured higher catalytic efficiency and more pronounced enantioselectivity than the “face-to-face” complex CuL2. The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL1, which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL1, even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics.

  14. Electrospun polylactic acid and polyvinyl alcohol fibers as efficient and stable nanomaterials for immobilization of lipases.

    PubMed

    Sóti, Péter Lajos; Weiser, Diana; Vigh, Tamás; Nagy, Zsombor Kristóf; Poppe, László; Marosi, György

    2016-03-01

    Electrospinning was applied to create easy-to-handle and high-surface-area membranes from continuous nanofibers of polyvinyl alcohol (PVA) or polylactic acid (PLA). Lipase PS from Burkholderia cepacia and Lipase B from Candida antarctica (CaLB) could be immobilized effectively by adsorption onto the fibrous material as well as by entrapment within the electrospun nanofibers. The biocatalytic performance of the resulting membrane biocatalysts was evaluated in the kinetic resolution of racemic 1-phenylethanol (rac-1) and 1-phenylethyl acetate (rac-2). Fine dispersion of the enzymes in the polymer matrix and large surface area of the nanofibers resulted in an enormous increase in the activity of the membrane biocatalyst compared to the non-immobilized crude powder forms of the lipases. PLA as fiber-forming polymer for lipase immobilization performed better than PVA in all aspects. Recycling studies with the various forms of electrospun membrane biocatalysts in ten cycles of the acylation and hydrolysis reactions indicated excellent stability of this forms of immobilized lipases. PLA-entrapped lipases could preserve lipase activity and enantiomer selectivity much better than the PVA-entrapped forms. The electrospun membrane forms of CaLB showed high mechanical stability in the repeated acylations and hydrolyses than commercial forms of CaLB immobilized on polyacrylamide beads (Novozyme 435 and IMMCALB-T2-150). PMID:26724947

  15. Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes.

    PubMed

    Xue, Shan-Shan; Zhao, Meng; Ke, Zhuo-Feng; Cheng, Bei-Chen; Su, Hua; Cao, Qian; Cao, Zhen-Kun; Wang, Jun; Ji, Liang-Nian; Mao, Zong-Wan

    2016-01-01

    It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1-S3) at neutral pH indicated that the "back-to-back" bisCD complex CuL(1) favoured higher catalytic efficiency and more pronounced enantioselectivity than the "face-to-face" complex CuL(2). The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL(1), which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL(1), even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics. PMID:26916830

  16. Acid distribution in phosphoric acid fuel cells

    SciTech Connect

    Okae, I.; Seya, A.; Umemoto, M.

    1996-12-31

    Electrolyte acid distribution among each component of a cell is determined by capillary force when the cell is not in operation, but the distribution under the current load conditions had not been clear so far. Since the loss of electrolyte acid during operation is inevitable, it is necessary to store enough amount of acid in every cell. But it must be under the level of which the acid disturbs the diffusion of reactive gases. Accordingly to know the actual acid distribution during operation in a cell is very important. In this report, we carried out experiments to clarify the distribution using small single cells.

  17. Development of Highly Potent GAT1 Inhibitors: Synthesis of Nipecotic Acid Derivatives by Suzuki-Miyaura Cross-Coupling Reactions.

    PubMed

    Petrera, Marilena; Wein, Thomas; Allmendinger, Lars; Sindelar, Miriam; Pabel, Jörg; Höfner, Georg; Wanner, Klaus T

    2016-03-01

    A new series of potent and selective mGAT1 inhibitors has been identified, featuring a nipecotic acid residue and an N-butenyl linker with a 2-biphenyl residue at the ω-position. Docking, combined with MD calculations, revealed a binding mode for the new compounds similar to that of tiagabine, the only mGAT1 inhibitor currently approved as antiepileptic drug. For the synthesis, a Suzuki-Miyaura cross-coupling reaction was used as a key step by which variously substituted biaryl subunits were assembled. Biological evaluation revealed several compounds that possess binding affinities and inhibitory potencies toward mGAT1, together with subtype selectivities against mGAT2-mGAT4 that were similar to or even higher than those for tiagabine. A derivative carrying the 2',4'-dichloro-2-biphenyl moiety attached to N-but-3-enylnipecotic acid at the terminal position of the linker chain was found to be the most potent binder, with the racemic form of the compound displaying a binding affinity of 8.05±0.13 (pKi ), while the R enantiomer exhibited an affinity value of 8.33±0.06 (pKi ). PMID:26683881

  18. A study of the metal binding capacity of saccharinic acids formed during the alkali catalysed decomposition of cellulosic materials: nickel complexation by glucoisosaccharinic acids and xyloisosaccharinic acids.

    PubMed

    Almond, Michael; Belton, Daniel; Humphreys, Paul N; Laws, Andrew P

    2016-06-01

    The stoichiometry of the metal complexes formed between nickel and the ligand β-glucoisosaccharinic acid (β-GISA) and a racemic mixture of enantiomers of xyloisosaccharinic acid (XISA) has been determined at both neutral and alkaline pHs. Bjerrum plots, Job's plots and conductance measurements indicated that for each of the systems one to one Ni(ligand) complexes were formed at near neutral pHs (<7.5). At intermediate alkaline pHs (7.5-13) there is evidence to support the formation and precipitation of Ni2(ligand)(OH)3 complexes, finally, at high pH (>13) sparingly soluble Ni2(ligand)(OH)4 complexes were formed. The stability constants for the Ni(β-GISA), Ni(α-GISA) and Ni(XISA) complexes formed at neutral pH were determined under identical conditions using polarographic studies. The measured stability constants for Ni(β-GISA) (log10 β = 1.94 ± 0.15) and for Ni(α-GISA)(log10 β = 2.07 ± 0.13) are very similar; the value measured for the Ni(XISA) complex (log10 β = 0.83) was an order of magnitude smaller. The stability constants for the Ni2(Ligand)(OH)4 complexes formed at highly alkaline pHs were determined using the Schubert method. The measured stability constant for Ni2(β-GISA)(OH)4 (log10 β = 30.6 ± 0.5) was an order of magnitude bigger than the value for Ni2(α-GISA)(OH)4 (log10 β = 29.0 ± 0.5) measured under identical conditions. Attempts to measure the stability constant for Ni2(XISA)(OH)4 were unsuccessful; Ni2(XISA)(OH)4 complexes were not present in significant amounts at high pH to allow the log10β value to be determined by the Schubert method. PMID:27107221

  19. Design and synthesis of inhibitors incorporating beta -amino acids of metalloendopeptidase EC 3.4.24.15.

    PubMed

    Steer, D L; Lew, R A; Perlmutter, P; Smith, A I; Aguilar, M I

    2000-09-01

    Endopeptidase EC 3.4.24.15 (EP 24.15) is a thermolysin-like metalloendopeptidase which is expressed widely throughout the body, with the highest concentrations in the brain, pituitary and testis. While the precise role of EP 24.15 remains unknown, it is thought to participate in the regulated metabolism of a number of specific neuropeptides. Of the limited number of inhibitors described for EP 24.15, N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-amino benzoate (CFP) is the most widely studied. CFP is a potent and specific inhibitor, but is unstable in vivo due to its cleavage between the alanine and tyrosine residues by the enzyme neprilysin (EP 24.11). The cpp-Ala-Ala N-terminal product of this cleavage is a potent inhibitor of angiotensin converting enzyme, which further limits the use of CFP in vivo. To generate specific inhibitors of EP 24.15 that are resistant to in vivo proteolysis by EP 24.11, beta-amino acids have been incorporated into the structure of CFP. We have prepared racemic mixtures of beta-amino acids containing proteogenic side chains, which are 9-fluorenylmethoxycarbonyl (Fmoc)-protected, and several analogues of CFP containing beta-amino acids have been synthesized by solid phase peptide synthesis. The results of stability and inhibitory studies of these new analogues show that the incorporation of beta-amino acids adjacent to the scissile bond can indeed stabilize the peptides against cleavage by EP 24.11 and still inhibit EP 24.15. The results obtained in these studies demonstrate the potential of these amino acids in the synthesis of peptidomimetics and in the design of new stable and specific therapeutics. PMID:11016884

  20. Environmentally Benign CO2-Based Copolymers: Degradable Polycarbonates Derived from Dihydroxybutyric Acid and Their Platinum-Polymer Conjugates.

    PubMed

    Tsai, Fu-Te; Wang, Yanyan; Darensbourg, Donald J

    2016-04-01

    (S)-3,4-Dihydroxybutyric acid ((S)-3,4-DHBA), an endogenous straight chain fatty acid, is a normal human urinary metabolite and can be obtained as a valuable chiral biomass for synthesizing statin-class drugs. Hence, its epoxide derivatives should serve as promising monomers for producing biocompatible polymers via alternating copolymerization with carbon dioxide. In this report, we demonstrate the production of poly(tert-butyl 3,4-dihydroxybutanoate carbonate) from racemic-tert-butyl 3,4-epoxybutanoate (rac-(t)Bu 3,4-EB) and CO2 using bifunctional cobalt(III) salen catalysts. The copolymer exhibited greater than 99% carbonate linkages, 100% head-to-tail regioselectivity, and a glass-transition temperature (Tg) of 37 °C. By way of comparison, the similarly derived polycarbonate from the sterically less congested monomer, methyl 3,4-epoxybutanoate, displayed 91.8% head-to-tail content and a lower Tg of 18 °C. The tert-butyl protecting group of the pendant carboxylate group was removed using trifluoroacetic acid to afford poly(3,4-dihydroxybutyric acid carbonate). Depolymerization of poly(tert-butyl 3,4-dihydroxybutanoate carbonate) in the presence of strong base results in a stepwise unzipping of the polymer chain to yield the corresponding cyclic carbonate. Furthermore, the full degradation of the acetyl-capped poly(potassium 3,4-dihydroxybutyrate carbonate) resulted in formation of the biomasses, β-hydroxy-γ-butyrolacetone and 3,4-dihydroxybutyrate, in water (pH = 8) at 37 °C. In addition, water-soluble platinum-polymer conjugates were synthesized with platinum loading of 21.3-29.5%, suggesting poly(3,4-dihydroxybutyric acid carbonate) and related derivatives may serve as platinum drug delivery carriers. PMID:26974858

  1. Abundance and expression of enantioselective rdpA and sdpA dioxygenase genes during degradation of the racemic herbicide (R,S)-2-(2,4-dichlorophenoxy)propionate in soil.

    PubMed

    Paulin, Mélanie M; Nicolaisen, Mette H; Sørensen, Jan

    2010-05-01

    The rdpA and sdpA genes encode two enantioselective alpha-ketoglutarate-dependent dioxygenases catalyzing the initial step of microbial degradation of the chiral herbicide (R,S)-2-(2,4-dichlorophenoxy)propionate (R,S-dichlorprop). Primers were designed to assess abundance and transcription dynamics of rdpA and sdpA genes in a natural agricultural soil. No indigenous rdpA genes were detected, but sdpA genes were present at levels of approximately 10(3) copies g of soil(-1). Cloning and sequencing of partial sdpA genes revealed a high diversity within the natural sdpA gene pool that could be divided into four clusters by phylogenetic analysis. BLASTp analysis of deduced amino acids revealed that members of cluster I shared 68 to 69% identity, cluster II shared 78 to 85% identity, cluster III shared 58 to 64% identity, and cluster IV shared 55% identity to their closest SdpA relative in GenBank. Expression of rdpA and sdpA in Delftia acidovorans MC1 inoculated in soil was monitored by reverse transcription quantitative real-time PCR (qPCR) during in situ degradation of 2 and 50 mg kg(-1) of (R,S)-dichlorprop. (R,S)-Dichlorprop amendment created a clear upregulation of both rdpA and sdpA gene expression during the active phase of (14)C-labeled (R,S)-dichlorprop mineralization, particularly following the second dose of 50 mg kg(-1) herbicide. Expression of both genes was maintained at a low constitutive level in nonamended soil microcosms. This study is the first to report the presence of indigenous sdpA genes recovered directly from natural soil and also comprises the first investigation into the transcription dynamics of two enantioselective dioxygenase genes during the in situ degradation of the herbicide (R,S)-dichlorprop in soil. PMID:20305027

  2. Acid tolerance in amphibians

    SciTech Connect

    Pierce, B.A.

    1985-04-01

    Studies of amphibian acid tolerance provide information about the potential effects of acid deposition on amphibian communities. Amphibians as a group appear to be relatively acid tolerant, with many species suffering increased mortality only below pH 4. However, amphibians exhibit much intraspecific variation in acid tolerance, and some species are sensitive to even low levels of acidity. Furthermore, nonlethal effects, including depression of growth rates and increases in developmental abnormalities, can occur at higher pH.

  3. Active-Site Engineering of ω-Transaminase for Production of Unnatural Amino Acids Carrying a Side Chain Bulkier than an Ethyl Substituent.

    PubMed

    Han, Sang-Woo; Park, Eul-Soo; Dong, Joo-Young; Shin, Jong-Shik

    2015-10-01

    ω-Transaminase (ω-TA) is a promising enzyme for use in the production of unnatural amino acids from keto acids using cheap amino donors such as isopropylamine. The small substrate-binding pocket of most ω-TAs permits entry of substituents no larger than an ethyl group, which presents a significant challenge to the preparation of structurally diverse unnatural amino acids. Here we report on the engineering of an (S)-selective ω-TA from Ochrobactrum anthropi (OATA) to reduce the steric constraint and thereby allow the small pocket to readily accept bulky substituents. On the basis of a docking model in which L-alanine was used as a ligand, nine active-site residues were selected for alanine scanning mutagenesis. Among the resulting variants, an L57A variant showed dramatic activity improvements in activity for α-keto acids and α-amino acids carrying substituents whose bulk is up to that of an n-butyl substituent (e.g., 48- and 56-fold increases in activity for 2-oxopentanoic acid and L-norvaline, respectively). An L57G mutation also relieved the steric constraint but did so much less than the L57A mutation did. In contrast, an L57V substitution failed to induce the improvements in activity for bulky substrates. Molecular modeling suggested that the alanine substitution of L57, located in a large pocket, induces an altered binding orientation of an α-carboxyl group and thereby provides more room to the small pocket. The synthetic utility of the L57A variant was demonstrated by carrying out the production of optically pure L- and D-norvaline (i.e., enantiomeric excess [ee]>99%) by asymmetric amination of 2-oxopantanoic acid and kinetic resolution of racemic norvaline, respectively. PMID:26231640

  4. Active-Site Engineering of ω-Transaminase for Production of Unnatural Amino Acids Carrying a Side Chain Bulkier than an Ethyl Substituent

    PubMed Central

    Han, Sang-Woo; Park, Eul-Soo; Dong, Joo-Young

    2015-01-01

    ω-Transaminase (ω-TA) is a promising enzyme for use in the production of unnatural amino acids from keto acids using cheap amino donors such as isopropylamine. The small substrate-binding pocket of most ω-TAs permits entry of substituents no larger than an ethyl group, which presents a significant challenge to the preparation of structurally diverse unnatural amino acids. Here we report on the engineering of an (S)-selective ω-TA from Ochrobactrum anthropi (OATA) to reduce the steric constraint and thereby allow the small pocket to readily accept bulky substituents. On the basis of a docking model in which l-alanine was used as a ligand, nine active-site residues were selected for alanine scanning mutagenesis. Among the resulting variants, an L57A variant showed dramatic activity improvements in activity for α-keto acids and α-amino acids carrying substituents whose bulk is up to that of an n-butyl substituent (e.g., 48- and 56-fold increases in activity for 2-oxopentanoic acid and l-norvaline, respectively). An L57G mutation also relieved the steric constraint but did so much less than the L57A mutation did. In contrast, an L57V substitution failed to induce the improvements in activity for bulky substrates. Molecular modeling suggested that the alanine substitution of L57, located in a large pocket, induces an altered binding orientation of an α-carboxyl group and thereby provides more room to the small pocket. The synthetic utility of the L57A variant was demonstrated by carrying out the production of optically pure l- and d-norvaline (i.e., enantiomeric excess [ee] > 99%) by asymmetric amination of 2-oxopantanoic acid and kinetic resolution of racemic norvaline, respectively. PMID:26231640

  5. Toxicity of adipic acid.

    PubMed

    Kennedy, Gerald L

    2002-05-01

    Adipic acid has very low acute toxicity in rats with an LD50 > 5000 mg/kg. Adipic acid produced mild to no skin irritation on intact guinea pig skin as a 50% concentration in propylene glycol; it was not a skin sensitizer. Adipic acid caused mild conjunctival irritation in washed rabbit eyes; in unwashed rabbit eyes, there was mild conjunctival irritation, minimal iritis, but no corneal effects. Adipic acid dust may irritate the mucous membranes of the lungs and nose. In a 2-year feeding study, rats fed adipic acid at concentrations up to 5% in the diet exhibited only weight loss. Adipic acid is not genetically active in a wide variety of assay systems. Adipic acid caused no developmental toxicity in mice, rats, rabbits, or hamsters when administered orally. Adipic acid is partially metabolized in humans; the balance is eliminated unchanged in the urine. Adipic acid is slightly to moderately toxic to fish, daphnia, and algae in acute tests. PMID:12024802

  6. Acid Thunder: Acid Rain and Ancient Mesoamerica

    ERIC Educational Resources Information Center

    Kahl, Jonathan D. W.; Berg, Craig A.

    2006-01-01

    Much of Mesoamerica's rich cultural heritage is slowly eroding because of acid rain. Just as water dissolves an Alka-Seltzer tablet, acid rain erodes the limestone surfaces of Mexican archaeological sites at a rate of about one-half millimeter per century (Bravo et al. 2003). A half-millimeter may not seem like much, but at this pace, a few…

  7. Quantity of acid in acid fog

    SciTech Connect

    Deal, W.J.

    1983-07-01

    This communication notes the actual magnitude of the acidity in acidic fog particles and suggests a possible line of inquiry into the health effects of such fog so that it can be determined whether a typical fog is detrimental or beneficial relative to dry air.

  8. [Amino acids in saliva].

    PubMed

    Klinger, G; Gruhn, K

    1984-01-01

    Total amino acids in saliva and free and peptide-bound amino acids from 21 saliva samples were determined. The contents of amino acids was 25 mmol/1; total nitrogen content was 78-80 mmol/1. Amino acids consist of Prolin in 25%. Some patients were examined before and after application of the depot estrogen ethinyl estradiosulfonat, which stimulates the assimilation of protein. After application, amino acids increased and the authors found a shift between the single amino acids. Estrogen medication induced an increase in proteins with the character of collagens. Clinical effects are discussed. (author's modified) PMID:6240853

  9. Design, synthesis and SAR studies of GABA uptake inhibitors derived from 2-substituted pyrrolidine-2-yl-acetic acids.

    PubMed

    Steffan, Tobias; Renukappa-Gutke, Thejavathi; Höfner, Georg; Wanner, Klaus T

    2015-03-15

    In this paper, we disclose the design and synthesis of a series of 2-substituted pyrrolidine-2-yl-acetic acid as core structures and the N-arylalkyl derivatives thereof as potential GABA transport inhibitors. The 2-position in the side chain of pyrrolidine-2-yl-acetic acid derivatives was substituted with alkyl, hydroxy and amino groups to modulate the activity and selectivity to mGAT1 and mGAT4 proteins. SAR studies of the compounds performed for the four mouse GABA transporter proteins (mGAT1-mGAT4) implied significant potencies and subtype selectivities for 2-hydroxy-2-pyrrolidine-2-yl-acetic acid derivatives. The racemate rac-(u)-13c exhibited the highest potency (pIC50 5.67) at and selectivity for mGAT1 in GABA uptake assays. In fact, the potency of rac-(u)-13c at hGAT-1 (pIC50 6.14) was even higher than its potency at mGAT1. These uptake results for rac-(u)-13c are in line with the binding affinities to the aforesaid proteins mGAT1 (pKi 6.99) and hGAT-1 (pKi 7.18) determined by MS Binding Assay based on NO711 as marker quantified by LC-ESI-MS-MS analysis. Interestingly, the 2-hydroxy-2-pyrrolidine-2-yl-acetic acid rac-(u)-13d containing 2-{[tris(4-methoxyphenyl)]methoxy} ethyl group at the nitrogen atom of the pyrrolidine ring showed high potency at mGAT4 and a comparatively better selectivity for this protein (>15 against mGAT3) than the well known mGAT4 uptake inhibitor (S)-SNAP-5114. PMID:25698617

  10. Bacterial utilization of L-sugars and D-amino acids

    NASA Astrophysics Data System (ADS)

    Pikuta, Elena V.; Hoover, Richard B.; Klyce, Brig; Davies, Paul C. W.; Davies, Pauline

    2006-08-01

    The fact that organotrophic organisms on Earth use L-amino acids and D-sugars as an energy source is recognized as one of the universal features of life. The chirality of organic molecules with asymmetric location of group-radicals was described a relatively long time ago. Louis Pasteur observed that abiotic (chemical) processes produced mixtures with equal numbers (racemic) of the two forms but that living organisms possessed a molecular asymmetry that included only one of the enantiomers (homochirality). He speculated that the origin of the asymmetry of chiral biomolecules might hold the key to the nature of life. All of the amino acids in proteins (except for Glycine which is symmetrical) exhibit the same absolute steric configuration as L-glyceraldehyde. D-amino acids are never found in proteins, although they do exist in nature and are often found in polypeptide antibiotics. Constitutional sugars of cells, opposite to the amino acids, are the D-enantiomers, and the appearance of L-sugars in Nature is extremely rare. Notwithstanding this fact, the metabolism of some bacteria does have the capability to use amino acids and sugars with alternative chirality. This property may be caused by the function of specific enzymes belonging to the class of isomerases (racemases, epimerases, isomerases, tautomerases). In our laboratory, we have investigated several anaerobic bacterial strains, and have found that some of these bacteria are capable of using D-amino acids and L-sugars. Strain BK1 is capable of growth on D-arginine, but its growth characteristics on L-arginine are approximately twice as high. Another alkaliphilic strain SCA T (= ATCC BAA-1084 T = JCM 12857 T = DSM 17722 T = CIP 107910 T) was found to be capable of growth on L-ribose and L-arabinose. It is interesting that this strain was incapable of growth on D-arabinose, which suggests the involvement of some alternative mechanism of enzyme activity. In this paper, we describe the preliminary results of

  11. Bacterial Utilization of L-sugars and D-amino Acids

    NASA Technical Reports Server (NTRS)

    Pikuta, Elena; Hoover, Richard B.; Klyce, Brig; Davies, Paul C. W.; Davies, Pauline

    2006-01-01

    The fact that organotrophic organisms on Earth use L-amino acids and D-sugars as an energy source is recognized as one of the universal features of life. The chirality of organic molecules with asymmetric location of group- radicals was described a relatively long time ago. In 1848, Louis Pasteur discovered chiral molecules when he investigated the way that crystals of sodium ammonium paratartrate rotated the plane of polarization of light. He found that the crystal structures represented the underlying asymmetry of molecules that existed in either lea-handed or right-handed forms (enantiomers). Pasteur observed that abiotic (chemical) processes produced mixtures with equal numbers (racemic) of the two forms but that living organisms possessed a molecular asymmetry that included only one of the enantiomers (homochirality). He speculated that the origin of the asymmetry of chiral biomolecules might hold the key to the nature of life. All of the amino acids in proteins (except for Glycine which is symmetrical) exhibit the same absolute steric configuration as L-glyceraldehyde. D-amino acids are never found in proteins, although they do exist in nature and are often found in polypeptide antibiotics. Constitutional sugars of cells, opposite to the amino acids, are the D-enantiomers, and the appearance of L-sugars in Nature is extremely rare. Notwithstanding this fact, the metabolism of some bacteria does have capability to use amino acids and sugars with alternative chirality. This property may be caused by the function of specific enzymes belonging to the class of isomerases (racemases, epimerases, isomerases, tautomerases). In our laboratory, we have investigated several anaerobic bacterial strains, and have found that some of these bacteria are capable of using D-amino acids and L-sugars. Strain BK1 is capable of growth on D-arginine, but its growth characteristics on L-arginine are approximately twice higher. Another alkaliphilic strain SCAT(sup T) (= ATCC BAA-1084

  12. A phase transition from monoclinic C2 with Z' = 1 to triclinic P1 with Z' = 4 for the quasiracemate L-2-aminobutyric acid-D-methionine (1/1).

    PubMed

    Görbitz, Carl Henrik; Wragg, David S; Bakke, Ingrid Marie Bergh; Fleischer, Christian; Grønnevik, Gaute; Mykland, Maria; Park, Yoomin; Trovik, Kristian Wiedicke; Serigstad, Halvard; Sundsli, Bård Edgar Vestheim

    2016-07-01

    Racemates of hydrophobic amino acids with linear side chains are known to undergo a unique series of solid-state phase transitions that involve sliding of molecular bilayers upon heating or cooling. Recently, this behaviour was shown to extend also to quasiracemates of two different amino acids with opposite handedness [Görbitz & Karen (2015). J. Phys. Chem. B, 119, 4975-4984]. Previous investigations are here extended to an L-2-aminobutyric acid-D-methionine (1/1) co-crystal, C4H9NO2·C5H11NO2S. The significant difference in size between the -CH2CH3 and -CH2CH2SCH3 side chains leads to extensive disorder at room temperature, which is essentially resolved after a phase transition at 229 K to an unprecedented triclinic form where all four D-methionine molecules in the asymmetric unit have different side-chain conformations and all three side-chain rotamers are used for the four partner L-2-aminobutyric acid molecules. PMID:27377274

  13. Hydrochloric acid poisoning

    MedlinePlus

    Hydrochloric acid is a clear, poisonous liquid. It is highly corrosive, which means it immediately causes severe damage, ... discusses poisoning due to swallowing or breathing in hydrochloric acid. This article is for information only. Do NOT ...

  14. Omega-3 Fatty Acids

    MedlinePlus

    Omega-3 fatty acids are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount ... the blood in people with very high triglycerides. Omega-3 fatty acids are in a class of medications ...

  15. Omega-6 Fatty Acids

    MedlinePlus

    Omega-6 fatty acids are types of fats. Some types are found in vegetable oils, including corn, evening primrose seed, safflower, and soybean oils. Other types of omega-6 fatty acids are found in black currant seed, borage seed, ...

  16. Zoledronic Acid Injection

    MedlinePlus

    Zoledronic acid (Reclast) is used to prevent or treat osteoporosis (condition in which the bones become thin and weak ... of life,' end of regular menstrual periods). Zoledronic acid (Reclast) is also used to treat osteoporosis in ...

  17. Aminolevulinic Acid Topical

    MedlinePlus

    Aminolevulinic acid is used in combination with photodynamic therapy (PDT; special blue light) to treat actinic keratoses (small crusty ... skin cancer) of the face or scalp. Aminolevulinic acid is in a class of medications called photosensitizing ...

  18. Acid-fast stain

    MedlinePlus

    The acid-fast stain is a laboratory test that determines if a sample of tissue, blood, or other body ... dye. The slide is then washed with an acid solution and a different stain is applied. Bacteria ...

  19. Uric acid - blood

    MedlinePlus

    Uric acid is a chemical created when the body breaks down substances called purines. Purines are found in some ... dried beans and peas, and beer. Most uric acid dissolves in blood and travels to the kidneys. ...

  20. Hydrochloric acid poisoning

    MedlinePlus

    Hydrochloric acid is a clear, poisonous liquid. It is highly corrosive, which means it immediately causes severe damage, such ... poisoning due to swallowing or breathing in hydrochloric acid. This article is for information only. Do NOT ...