Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

PubMed Central

Wünsch, Matthias; Schröder, David; Fröhr, Tanja; Teichmann, Lisa; Hedwig, Sebastian; Janson, Nils; Belu, Clara; Simon, Jasmin; Heidemeyer, Shari; Holtkamp, Philipp; Rudlof, Jens; Klemme, Lennard; Hinzmann, Alessa; Neumann, Beate; Stammler, Hans-Georg

2017-01-01

The amide moiety of peptides can be replaced for example by a triazole moiety, which is considered to be bioisosteric. Therefore, the carbonyl moiety of an amino acid has to be replaced by an alkyne in order to provide a precursor of such peptidomimetics. As most amino acids have a chiral center at Cα, such amide bond surrogates need a chiral moiety. Here the asymmetric synthesis of a set of 24 N-sulfinyl propargylamines is presented. The condensation of various aldehydes with Ellman’s chiral sulfinamide provides chiral N-sulfinylimines, which were reacted with (trimethylsilyl)ethynyllithium to afford diastereomerically pure N-sulfinyl propargylamines. Diverse functional groups present in the propargylic position resemble the side chain present at the Cα of amino acids. Whereas propargylamines with (cyclo)alkyl substituents can be prepared in a direct manner, residues with polar functional groups require suitable protective groups. The presence of particular functional groups in the side chain in some cases leads to remarkable side reactions of the alkyne moiety. Thus, electron-withdrawing substituents in the Cα-position facilitate a base induced rearrangement to α,β-unsaturated imines, while azide-substituted propargylamines form triazoles under surprisingly mild conditions. A panel of propargylamines bearing fluoro or chloro substituents, polar functional groups, or basic and acidic functional groups is accessible for the use as precursors of peptidomimetics. PMID:29234470

Dihydrogenphosphate recognition: Assistance from the acidic OH moiety of the anion

NASA Astrophysics Data System (ADS)

Das, Rituraj; Pathak, Nibedan; Choudhury, Samarjit; Borah, Suchibrata; Mahanta, Sanjeev Pran

2017-11-01

The binding affinity of the acidic hydrogen i.e. OH moiety of dihydrogenphosphate was investigated with receptors having competent H-bond donor and H-bond acceptor component. Three derivatives of 2, 3-dipyrrol-2‧-ylquinoxaline substituted with H-bond acceptor moiety at pyrrole α- positions were synthesized and their dihydrogenphosphate affinity was studied. All the three receptors shows general affinity towards fluoride, acetate and cyanide ions in DMSO solution. Interestingly, formyl substitution at both the pyrrole α-positions of 2, 3-dipyrrol-2‧-ylquinoxaline leads to binding of H2PO4-. 1H-NMR study rules out the involvement of the H-bond donor unit of the receptor in the biding event and reveals that the binding occurs predominantly via the Osbnd H⋯O interaction between the acidic OH moiety of the anion and the Cdbnd O of the formyl group of the receptor.

Large birefringence and polarization holographic gratings formed in photocross-linkable polymer liquid crystals comprising bistolane mesogenic side groups

NASA Astrophysics Data System (ADS)

Emoto, Akira; Matsumoto, Taro; Yamashita, Ayumi; Shioda, Tatsutoshi; Ono, Hiroshi; Kawatsuki, Nobuhiro

2009-10-01

Polarization gratings with large birefringence are formed in photoreactive polymer liquid crystals with bistolane moiety and terminal cinnamic acid moiety by the use of polarized ultraviolet interference light and subsequent annealing. The polarized ultraviolet light causes the axis-selective photoreaction between the cinnamic acid groups and subsequent annealing induce the reorientation of peripheral molecules without cross-linking along the cross-linked groups. Long bistolane mesogenic moiety exhibits large birefringence in comparison with a biphenyl mesogenic moiety, the value of the induced birefringence in the bistolane mesogenic liquid crystalline (LC) polymer is strongly dependent on both the grating constant and the wavelength of the reconstruction light.

Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis.

PubMed

Takeda, Shuso; Misawa, Koichiro; Yamamoto, Ikuo; Watanabe, Kazuhito

2008-09-01

In the present study it was revealed that cannabidiolic acid (CBDA) selectively inhibited cyclooxygenase (COX)-2 activity with an IC(50) value (50% inhibition concentration) around 2 microM, having 9-fold higher selectivity than COX-1 inhibition. In contrast, Delta(9)-tetrahydrocannabinolic acid (Delta(9)-THCA) was a much less potent inhibitor of COX-2 (IC(50) > 100 microM). Nonsteroidal anti-inflammatory drugs containing a carboxyl group in their chemical structures such as salicylic acid are known to inhibit nonselectively both COX-1 and COX-2. CBDA and Delta(9)-THCA have a salicylic acid moiety in their structures. Thus, the structural requirements for the CBDA-mediated COX-2 inhibition were next studied. There is a structural difference between CBDA and Delta(9)-THCA; phenolic hydroxyl groups of CBDA are freed from the ring formation with the terpene moiety, although Delta(9)-THCA has dibenzopyran ring structure. It was assumed that the whole structure of CBDA is important for COX-2 selective inhibition because beta-resorcylic acid itself did not inhibit COX-2 activity. Methylation of the carboxylic acid moiety of CBDA led to disappearance of COX-2 selectivity. Thus, it was suggested that the carboxylic acid moiety in CBDA is a key determinant for the inhibition. Furthermore, the crude extract of cannabis containing mainly CBDA was shown to have a selective inhibitory effect on COX-2. Taken together, these lines of evidence in this study suggest that naturally occurring CBDA in cannabis is a selective inhibitor for COX-2.

Influence of the amino acid moiety on deconjugation of bile acid amidates by cholylglycine hydrolase or human fecal cultures.

PubMed

Huijghebaert, S M; Hofmann, A F

1986-07-01

The influence of the chemical structure of the amino acid (or amino acid analogue) moiety of a number of synthetic cholyl amidates on deconjugation by cholylglycine hydrolase from Clostridium perfringens was studied in vitro at pH 5.4. Conjugates with alkyl homologues of glycine were hydrolyzed more slowly as the number of methylene units increased (cholylglycine greater than cholyl-beta-alanine greater than cholyl-gamma-aminobutyrate). In contrast, for conjugates with the alkyl homologues of taurine, cholylaminopropane sulfonate was hydrolyzed slightly faster than cholyltaurine, whereas cholylaminomethane sulfonate was hydrolyzed much more slowly. When glycine was replaced by other neutral alpha-amino acids, rates of hydrolysis decreased with increasing steric hindrance near the amide bond (cholyl-L-alpha-alanine much much greater than cholyl-L-leucine much greater than cholyl-L-valine greater than cholyl-L-tyrosine much greater than cholyl-D-valine). Conjugation with acidic or basic amino acids also greatly reduced the rates of hydrolysis, as cholyl-L-aspartate, cholyl-L-cysteate, cholyl-L-lysine, and cholyl-L-histidine were all hydrolyzed at a rate less than one-tenth that of cholylglycine. Methyl esterification of the carboxylic group of the amino acid moiety reduced the hydrolysis, but such substrates (cholylglycine methyl ester and cholyl-beta-alanine methyl ester) were completely hydrolyzed after overnight incubation with excess of enzyme. In contrast, cholyl-cholamine was not hydrolyzed at all, suggesting that a negative charge at the end of the side chain is required for optimal hydrolysis. Despite the lack of specificity for the amino acid moiety, a bile salt moiety was required, as the cholylglycine hydrolase did not display general carboxypeptidase activity for other non-bile acid substrates containing a terminal amide bond: hippuryl-L-phenylalanine and hippuryl-L-arginine, as well as oleyltaurine and oleylglycine, were not hydrolyzed. Fecal bacterial cultures from healthy volunteers also hydrolyzed cholyl-L-valine and cholyl-D-valine more slowly than cholylglycine, suggesting that cholylglycine hydrolase from Clostridium perfringens has a substrate specificity similar to that of the deconjugating enzymes of the fecal flora. The results indicate that modification of the position of the amide bond, introduction of steric hindrance near the amide bond, or loss of a negative charge on the terminal group of the amino acid moiety of the bile acid conjugate greatly reduces the rate of bacterial deconjugation in vitro when compared to that of the naturally occurring glycine and taurine conjugates.

Cysteine-containing peptide tag for site-specific conjugation of proteins

DOEpatents

Backer, Marina V.; Backer, Joseph M.

2008-04-08

The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety bound to the targeting moiety; the biological conjugate having a covalent bond between the thiol group of SEQ ID NO:2 and a functional group in the binding moiety. The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety that comprises an adapter protein, the adapter protein having a thiol group; the biological conjugate having a disulfide bond between the thiol group of SEQ ID NO:2 and the thiol group of the adapter protein. The present invention is also directed to biological sequences employed in the above biological conjugates, as well as pharmaceutical preparations and methods using the above biological conjugates.

Cysteine-containing peptide tag for site-specific conjugation of proteins

DOEpatents

Backer, Marina V.; Backer, Joseph M.

2010-10-05

The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety bound to the targeting moiety; the biological conjugate having a covalent bond between the thiol group of SEQ ID NO:2 and a functional group in the binding moiety. The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety that comprises an adapter protein, the adapter protein having a thiol group; the biological conjugate having a disulfide bond between the thiol group of SEQ ID NO:2 and the thiol group of the adapter protein. The present invention is also directed to biological sequences employed in the above biological conjugates, as well as pharmaceutical preparations and methods using the above biological conjugates.

NSAID-derived γ-secretase modulation requires an acidic moiety on the carbazole scaffold.

PubMed

Zall, Andrea; Kieser, Daniel; Höttecke, Nicole; Naumann, Eva C; Thomaszewski, Binia; Schneider, Katrin; Steinbacher, Dirk T; Schubenel, Robert; Masur, Stefan; Baumann, Karlheinz; Schmidt, Boris

2011-08-15

Modulation of γ-secretase activity holds potential for the treatment of Alzheimer's disease. Most NSAID-derived γ-secretase modulators feature a carboxylic acid, which may impair blood-brain barrier permeation. The structure activity relationship of 33 carbazoles featuring diverse carboxylic acid isosteres or metabolic precursors thereof was established in a cellular amyloid secretion assay. The modulatory activity was observed for acidic moieties and metabolically labile esters only, which supports our hypothesis of an acid-lysine interaction to be relevant for this type of γ-secretase modulators. Copyright © 2011 Elsevier Ltd. All rights reserved.

Molecular modelling for the design of chimaeric biomimetic dye-ligands and their interaction with bovine heart mitochondrial malate dehydrogenase.

PubMed Central

Labrou, N E; Eliopoulos, E; Clonis, Y D

1996-01-01

Molecular modelling and kinetic inhibition studies, as well as KD determinations by both difference-spectra and enzyme-inactivation studies, were employed to assess the ability of purpose-designed chimaeric biomimetic dyes (BM dyes) to act as affinity ligands for bovine heart L-malate dehydrogenase (MDH). Each BM dye was composed of two enzyme-recognition moieties. The terminal biomimetic moiety bore a carboxyl or a keto acid structure linked to the triazine ring, thus mimicking the substrate of MDH. The chromophore anthraquinone moiety remained unchanged and the same as that of the parent dye Vilmafix Blue A-R (VBAR), recognizing the nucleotide-binding site of MDH. The monochlorotriazine BM dyes did not inactivate MDH but competitively inhibited inactivation by the parent dichlorotriazine dye VBAR. Dye binding to MDH was accompanied by a characteristic spectral change in the range 500-850 nm. This phenomenon was reversed after titration with increasing amounts of NADH. When compared with VBAR, Cibacron Blue 3GA and two control non-biomimetic anthraquinone dyes, all BM dyes exhibited lower KD values and therefore higher affinity for MDH. The enzyme bound preferably to BM ligands substituted with a biomimetic aromatic moiety bearing an alpha-keto acid group and an amide linkage, rather than a monocarboxyl group. Thus the biomimetic dye bearing p-aminobenzyloxanilic acid as its terminal biomimetic moiety (BM5) exhibited the highest affinity (KD 1.3 microM, which corresponded to a 219-fold decrease over the KD of a control dye). BM5 displayed competitive inhibition with respect to both NADH (Ki 2.7 microM) and oxaloacetate (Ki 9.6 microM). A combination of molecular modelling and experimental studies has led to certain conclusions. The positioning of the dye in the enzyme is primarily achieved by the recognition and positioning of the nucleotide-pseudomimetic anthraquinone moiety. The hydrophobic groups of the dye provide the driving force for positioning of the ketocarboxyl biomimetic moiety. A match between the alternating polar and hydrophobic regions of the enzyme binding site with those of the biomimetic moiety is desirable. The length of the biomimetic moiety should be conserved in order for the keto acid to approach the enzyme active site and form charge-charge interactions. PMID:8615849

Polymers functionalized with bronsted acid groups

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Humbeck, Jeffrey; Long, Jeffrey R.; McDonald, Thomas M.

Porous aromatic framework polymers functionalized with Bronsted acid moieties are prepared by polymerization of a three-dimensional organic aryl or heteroaryl monomer and its copolymerization with a second aryl or heteroaryl monomer functionalized with one or more Bronsted acid moiety. The polymers are characterized by a stable three-dimensional structure, which, in exemplary embodiments, includes interpenetrating subunits within one or more domain of the bulk polymer structure. The polymers are of use in methods of adsorbing ammonia and amines and in devices and systems configured for this purpose.

Isoxazole moiety in the linker region of HDAC inhibitors adjacent to the Zn-chelating group: effects on HDAC biology and antiproliferative activity.

PubMed

Tapadar, Subhasish; He, Rong; Luchini, Doris N; Billadeau, Daniel D; Kozikowski, Alan P

2009-06-01

A series of hydroxamic acid based histone deacetylase inhibitors 6-15, containing an isoxazole moiety adjacent to the Zn-chelating hydroxamic acid, is reported herein. Some of these compounds showed nanomolar activity in the HDAC isoform inhibitory assay and exhibited micro molar inhibitory activity against five pancreatic cancer cell lines.

Conformation-Based Design and Synthesis of Apratoxin A Mimetics Modified at the α,β-Unsaturated Thiazoline Moiety.

PubMed

Onda, Yuichi; Masuda, Yuichi; Yoshida, Masahito; Doi, Takayuki

2017-08-10

We have demonstrated design, synthesis, and biological evaluation of apratoxin A mimetics. In the first generation, the moCys moiety was replaced with seven simple amino acids as their 3D structures can be similar to that of apratoxin A. Apratoxins M1-M7 were synthesized using solid-phase peptide synthesis and solution-phase macrolactamization. Apratoxin M7, which contains a piperidinecarboxylic acid moiety, exhibited potent cytotoxicity against HCT-116 cells. In the second generation, substitution of each amino acid residue in the tripeptide Tyr(Me)-MeAla-MeIle moiety in apratoxin M7 led to the development of the highly potent apratoxin M16 possessing biphenylalanine (Bph) instead of Tyr(Me), which exhibited an IC 50 value of 1.1 nM against HCT-116 cells. Moreover, compared to apratoxin A, apratoxin M16 exhibited a similarly high level of growth inhibitory activity against various cancer cell lines. The results indicate that apratoxin M16 could be a potential candidate as an anticancer agent.

TNT Biodegradation by Natural Microbial Assemblages at Estuarine Frontal Boundaries

DTIC Science & Technology

2012-07-02

component acid, aldehyde , and ketone phenols after microwave assisted CuO-oxidation (Louchouarn et al. 2000, Goni and Montgomery 2000). Phenols...Oahu, HI, USA (20 July 2010). vii LIST OF ACRONYMS Ac:Ad: Ratio of Acid to Aldehyde Moieties ASI: Air-Sea Interface BIX: Biological... aldehyde moieties for vanillyl phenols (Ac:Alv), an index of oxidative degradation for lignin, was positively correlated with fraction of C1 in the

Compositions for enhancing hydroysis of cellulosic material by cellulolytic enzyme compositions

DOEpatents

Quinlan, Jason; Xu, Feng; Sweeney, Matthew; Johansen, Katja Salomon

2014-09-30

The present invention relates to compositions comprising a GH61 polypeptide having cellulolytic enhancing activity and an organic compound comprising a carboxylic acid moiety, a lactone moiety, a phenolic moiety, a flavonoid moiety, or a combination thereof, wherein the combination of the GH61 polypeptide having cellulolytic enhancing activity and the organic compound enhances hydrolysis of a cellulosic material by a cellulolytic enzyme compared to the GH61 polypeptide alone or the organic compound alone. The present invention also relates to methods of using the compositions.

Antiproliferative activity and SARs of caffeic acid esters with mono-substituted phenylethanols moiety.

PubMed

Xie, Jin; Yang, Fengzhi; Zhang, Man; Lam, Celine; Qiao, Yixue; Xiao, Jia; Zhang, Dongdong; Ge, Yuxuan; Fu, Lei; Xie, Dongsheng

2017-01-15

A series of CAPE derivatives with mono-substituted phenylethanols moiety were synthesized and evaluated by MTT assay on growth of 4 human cancer cell lines (Hela, DU-145, MCF-7 and ECA-109). The substituent effects on the antiproliferative activity were systematically investigated for the first time. It was found that electron-donating and hydrophobic substituents at 2'-position of phenylethanol moiety could significantly enhance CAPE's antiproliferative activity. 2'-Propoxyl derivative, as a novel caffeic acid ester, exhibited exquisite potency (IC 50 =0.4±0.02 & 0.6±0.03μM against Hela and DU-145 respectively). Copyright © 2016 Elsevier Ltd. All rights reserved.

Laboratory Graduate Fellowship Program, 1989. Appendix D, Part 1. Certifications and Concurrence

DTIC Science & Technology

1989-01-01

takes place in nitric acid/sulfuric acid at degrees C for 3 hours. Nitration occurs both ortho and para the acetanilide (NHAc) moiety. This was...unexpected as acetanilide is usually a strong para director. Currently we preparing bulkier diamides using isobutyric anhydride and trimethylacetic...C for 3 hours. Nitration occurs both ortho and para t the acetanilide (NHAc) moiety. This was unexpected as acetanilide is usually a strong para

Surface decorations of poly(amidoamine) dendrimer by various pendant moieties for improved delivery of nucleic acid materials.

PubMed

Dehshahri, Ali; Sadeghpour, Hossein

2015-08-01

In recent years, the discovery of novel nucleic acid-based drug candidates (e.g., siRNA and miRNA) and the groundbreaking studies for somatic cell reprogramming into a state of pluripotency have led to reconsideration for the use of human gene therapy as a new paradigm with great therapeutic potential. However, the success of gene therapy is dependent on overcoming intra- and extracellular barriers hampering the efficient delivery of nucleic acid therapeutics into the target cells or tissues. Despite relatively low transfection efficiency, great attention has been directed to cationic polymers and dendrimers due to their ability to condense DNA and RNA molecules into nano-sized particles which is a necessary prerequisite for efficient transfer of nucleic acids into cells. These gene carriers show remarkable adaptability and significant capacity to transfer larger sizes of nucleic acid materials. Polyamidoamine (PAMAM) dendrimer has been employed as non-viral gene carrier due to its globular shape and well-defined structure containing abundant amino surface groups which provide possibility for surface decoration of the dendrimer via the conjugation of various moieties. In this review, we have brought out the various functionalization strategies of the PAMAM surface amines using different pendant moieties such as amino acids, proteins, cyclodextrins, and hydrophobic units in order to overcome intra- and extracellular barriers. These surface-decorated dendrimers possessing favorable properties provide substantial information and insight for redesigning existing dendrimers and polymers. By understanding the role played by the conjugated moieties, more efficient and novel designs of gene vehicles may be possible. Copyright © 2015 Elsevier B.V. All rights reserved.

Separation of anionic oligosaccharides by high-performance liquid chromatography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, E.D.; Baenziger, J.U.

1986-10-01

The authors have developed methods for rapid fractionation of anionic oligosaccharides containing sulfate and/or sialic acid moieties by high-performance liquid chromatography (HPLC). Ion-exchange HPLC on amine-bearing columns (Micropak AX-10 and AX-5) at pH 4.0 is utilized to separate anionic oligosaccharides bearing zero, one, two, three, or four charges, independent of the identity of the anionic moieties (sulfate and/or sialic acid). Ion-exchange HPLC at pH 1.7 allows separation of neutral, mono-, di-, and tetrasialylated, monosulfated, and disulfated oligosaccharides. Oligosaccharides containing three sialic acid residues and those bearing one each of sulfate and sialic acid, however, coelute at pH 1.7. Since themore » latter two oligosaccharide species separate at pH 4.0, analysis at pH 4.0 followed by analysis at pH 1.7 can be utilized to completely fractionate complex mixtures of sulfated and sialylated oligosaccharides. Ion-suppression amine adsorption HPLC has previously been shown to separate anionic oligosaccharides on the basis of net carbohydrate content (size). In this study they demonstrate the utility of ion-suppression amine adsorption HPLC for resolving sialylated oligosaccharide isomers which differ only in the linkages of sialic acid residues (..cap alpha..2,3 vs ..cap alpha..2,6) and/or location of ..cap alpha..2,3- and ..cap alpha..2,6-linked sialic acid moieties on the peripheral branches of oligosaccharides. These two methods can be used in tandem to separate oligosaccharides, both analytically and preparatively, based on their number, types, and linkages of anionic moieties.« less

Enantioselective recognition of mandelic acid by a 3,6-dithiophen-2-yl-9H-carbazole-based chiral fluorescent bisboronic acid sensor.

PubMed

Wu, Yubo; Guo, Huimin; James, Tony D; Zhao, Jianzhang

2011-07-15

We have prepared chiral fluorescent bisboronic acid sensors with 3,6-dithiophen-2-yl-9H-carbazole as the fluorophore. The thiophene moiety was used to extend the π-conjugation framework of the fluorophore in order to red-shift the fluorescence emission and, at the same time, to enhance the novel process where the fluorophore serves as the electron donor of the photoinduced electron transfer process (d-PET) of the boronic acid sensors; i.e., the background fluorescence of the sensor 1 at acidic pH is weaker compared to that at neutral or basic pH, in stark contrast to the typical a-PET boronic acid sensors (where the fluorophore serves as the electron acceptor of the photoinduced electron transfer process). The benefit of the d-PET boronic acid sensors is that the recognition of the hydroxylic acids can be achieved at acidic pH. We found that the thiophene moiety is an efficient π-conjugation linker and electron donor; as a result, the d-PET contrast ratio of the sensors upon variation of the pH is improved 10-fold when compared to the previously reported d-PET sensors without the thiophene moiety. Enantioselective recognition of tartaric acid was achieved at acid pH, and the enantioselectivity (total response K(D)I(F)(D)/K(L)I(F)(L)) is 3.3. The fluorescence enhancement (I(F)(Sample)/I(F)(Blank)) of sensor 1 upon binding with tartaric acid is 3.5-fold at pH 3.0. With the fluorescent bisboronic acid sensor 1, enantioselective recognition of mandelic acid was achieved for the first time. To the best of our knowledge, this is the first time that the mandelic acid has been enantioselectively recognized using a chiral fluorescent boronic acid sensor. Chiral monoboronic acid sensor 2 and bisboronic acid sensor 3 without the thiophene moiety failed to enantioselectively recognize mandelic acid. Our findings with the thiophene-incorporated boronic acid sensors will be important for the design of d-PET fluorescent sensors for the enantioselective recognition of α-hydroxylic acids such as mandelic acid, given that it is currently a challenge to recognize these analytes with boronic acid fluorescent molecular sensors.

21 CFR 184.1702 - Sheanut oil.

Code of Federal Regulations, 2010 CFR

2010-04-01

... acid moiety at the 2-position and saturated fatty acids, usually stearic or palmitic acids, at the 1...) Unsaponifiable matter not to exceed 1.5 percent, (4) Free fatty acids not more than 0.1 percent as oleic acid, (5...

21 CFR 184.1702 - Sheanut oil.

Code of Federal Regulations, 2011 CFR

2011-04-01

... acid moiety at the 2-position and saturated fatty acids, usually stearic or palmitic acids, at the 1...) Unsaponifiable matter not to exceed 1.5 percent, (4) Free fatty acids not more than 0.1 percent as oleic acid, (5...

Synthesis and Characterization of Organic Dyes Containing Various Donors and Acceptors

PubMed Central

Wu, Tzi-Yi; Tsao, Ming-Hsiu; Chen, Fu-Lin; Su, Shyh-Gang; Chang, Cheng-Wen; Wang, Hong-Paul; Lin, Yuan-Chung; Ou-Yang, Wen-Chung; Sun, I-Wen

2010-01-01

New organic dyes comprising carbazole, iminodibenzyl, or phenothiazine moieties, respectively, as the electron donors, and cyanoacetic acid or acrylic acid moieties as the electron acceptors/anchoring groups were synthesized and characterized. The influence of heteroatoms on carbazole, iminodibenzyl and phenothiazine donors, and cyano-substitution on the acid acceptor is evidenced by spectral, electrochemical, photovoltaic experiments, and density functional theory calculations. The phenothiazine dyes show solar-energy-to-electricity conversion efficiency (η) of 3.46–5.53%, whereas carbazole and iminodibenzyl dyes show η of 2.43% and 3.49%, respectively. PMID:20162019

Contribution of acidic components to the total acid number (TAN) of bio-oil

DOE PAGES

Park, Lydia K-E.; Liu, Jiaojun; Yiacoumi, Sotira; ...

2017-03-28

Bio-oil or pyrolysis oil — a product of thermochemical decomposition of biomass under oxygen-limited conditions — holds great potential to be a substitute for nonrenewable fossil fuels. But, its high acidity, which is primarily due to the degradation of hemicelluloses, limits its applications. For the evaluation of bio-oil production and treatment, it is essential to accurately measure the acidity of bio-oil. The total acid number (TAN), which is defined as the amount of potassium hydroxide needed to titrate one gram of a sample and has been established as an ASTM method to measure the acidity of petroleum products, has beenmore » employed to investigate the acidity of bio-oil. The TAN values of different concentrations of bio-oil components such as standard solutions of acetic acid, propionic acid, vanillic acid, hydroxybenzoic acid, syringic acid, hydroxymethylfurfural, and phenol were analyzed according to the ASTM D664 standard method. Our method showed the same linear relationship between the TAN values and the molar concentrations of acetic, propionic, and hydroxybenzoic acids. A different linear relationship was found for vanillic acid, due to the presence of multiple functional groups that can contribute to the TAN value. Furthermore, the influence of the titration solvent on the TAN values has been determined by comparing the TAN values and titration curves obtained from the standard method with results from the TAN analysis in aqueous environment and with equilibrium modeling results. Aqueous bio-oil samples with a known amount of acetic acid added were also analyzed. The additional acetic acid in bio-oil samples caused a proportional increase in the TAN values. These results of this research indicate that the TAN value of a sample with acids acting as monoprotic acids in the titration solvent can be converted to the molar concentration of total acids. For a sample containing acids that act as diprotic and polyprotic acids, however, its TAN value cannot be simply converted to the molar concentration of total acids because these acids have a stronger contribution to the TAN values than the contribution of monoprotic acids.« less

Contribution of acidic components to the total acid number (TAN) of bio-oil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Lydia K-E.; Liu, Jiaojun; Yiacoumi, Sotira

Bio-oil or pyrolysis oil — a product of thermochemical decomposition of biomass under oxygen-limited conditions — holds great potential to be a substitute for nonrenewable fossil fuels. But, its high acidity, which is primarily due to the degradation of hemicelluloses, limits its applications. For the evaluation of bio-oil production and treatment, it is essential to accurately measure the acidity of bio-oil. The total acid number (TAN), which is defined as the amount of potassium hydroxide needed to titrate one gram of a sample and has been established as an ASTM method to measure the acidity of petroleum products, has beenmore » employed to investigate the acidity of bio-oil. The TAN values of different concentrations of bio-oil components such as standard solutions of acetic acid, propionic acid, vanillic acid, hydroxybenzoic acid, syringic acid, hydroxymethylfurfural, and phenol were analyzed according to the ASTM D664 standard method. Our method showed the same linear relationship between the TAN values and the molar concentrations of acetic, propionic, and hydroxybenzoic acids. A different linear relationship was found for vanillic acid, due to the presence of multiple functional groups that can contribute to the TAN value. Furthermore, the influence of the titration solvent on the TAN values has been determined by comparing the TAN values and titration curves obtained from the standard method with results from the TAN analysis in aqueous environment and with equilibrium modeling results. Aqueous bio-oil samples with a known amount of acetic acid added were also analyzed. The additional acetic acid in bio-oil samples caused a proportional increase in the TAN values. These results of this research indicate that the TAN value of a sample with acids acting as monoprotic acids in the titration solvent can be converted to the molar concentration of total acids. For a sample containing acids that act as diprotic and polyprotic acids, however, its TAN value cannot be simply converted to the molar concentration of total acids because these acids have a stronger contribution to the TAN values than the contribution of monoprotic acids.« less

Perfluorooctanoic acid and environmental risks

EPA Science Inventory

Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acids (PFAA) family of chemicals, which consist of a carbon backbone typically four to fourteen carbons in length and a charged functional moiety.

Thermodynamic Analysis of the Selectivity Enhancement Obtained by Using Smart Hydrogels That Are Zwitterionic When Detecting Glucose With Boronic Acid Moieties

PubMed Central

Horkay, F.; Cho, S. H.; Tathireddy, P.; Rieth, L.; Solzbacher, F.; Magda, J.

2011-01-01

Because the boronic acid moiety reversibly binds to sugar molecules and has low cytotoxicity, boronic acid-containing hydrogels are being used in a variety of implantable glucose sensors under development, including sensors based on optical, fluorescence, and swelling pressure measurements. However, some method of glucose selectivity enhancement is often necessary, because isolated boronic acid molecules have a binding constant with glucose that is some forty times smaller than their binding constant with fructose, the second most abundant sugar in the human body. In many cases, glucose selectivity enhancement is obtained by incorporating pendant tertiary amines into the hydrogel network, thereby giving rise to a hydrogel that is zwitterionic at physiological pH. However, the mechanism by which incorporation of tertiary amines confers selectivity enhancement is poorly understood. In order to clarify this mechanism, we use the osmotic deswelling technique to compare the thermodynamic interactions of glucose and fructose with a zwitterionic smart hydrogel containing boronic acid moieties. We also investigate the change in the structure of the hydrogel that occurs when it binds to glucose or to fructose using the technique of small angle neutron scattering. PMID:22190765

The effect of albumin on podocytes: The role of the fatty acid moiety and the potential role of CD36 scavenger receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pawluczyk, I.Z.A., E-mail: izap1@le.ac.uk; John Walls Renal Unit, Leicester General Hospital Leicester; Pervez, A.

Evidence is emerging that podocytes are able to endocytose proteins such as albumin using kinetics consistent with a receptor-mediated process. To date the role of the fatty acid moiety on albumin uptake kinetics has not been delineated and the receptor responsible for uptake is yet to be identified. Albumin uptake studies were carried out on cultured human podocytes exposed to FITC-labelled human serum albumin either carrying fatty acids (HSA{sub +FA}) or depleted of them (HSA{sub −FA}). Receptor-mediated endocytosis of FITC-HSA{sub +FA} over 60 min was 5 times greater than that of FITC-HSA{sub −FA}. 24 h exposure of podocytes to albuminmore » up-regulated nephrin expression and induced the activation of caspase-3. These effects were more pronounced in response to HSA{sub −FA.} Individually, anti-CD36 antibodies had no effect upon endocytosis of FITC-HSA. However, a cocktail of 2 antibodies reduced uptake by nearly 50%. Albumin endocytosis was enhanced in the presence of the CD36 specific inhibitor sulfo-N-succinimidyl oleate (SSO) while knock-down of CD36 using CD36siRNA had no effect on uptake. These data suggest that receptor-mediated endocytosis of albumin by podocytes is regulated by the fatty acid moiety, although, some of the detrimental effects are induced independently of it. CD36 does not play a direct role in the uptake of albumin. - Highlights: • The fatty acid moiety is essential for receptor mediated endocytosis of albumin. • Fatty acid depleted albumin is more pathogenic to podocytes. • CD36 is not directly involved in albumin uptake by podocytes.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Battey, J.F.

When host and algal triglycerides synthesized in the symbiotic sea anemone Condylactis gigantea during light and dark incubations in /sup 14/C-bicarbonate and /sup 14/C-acetate were deacylated, more then 80% of the radioactivity was found in the fatty acid moiety. In contrast, triglycerides isolated from zooxanthellae and host incubated in /sup 14/C-glycerol in the dark were found to have more then 95% of their radioactivity in the glycerol moiety. During /sup 14/C-glycerol incubations in the light, radioactivity in the fatty acid moiety of zooxanthellae triglyceride fatty acid moiety stayed below 5% during /sup 14/C-glycerol incubations in the light. These results showmore » neither the zooxanthellae nor host can rapidly convert glycerol to fatty acid. Radioactivity from /sup 14/C-glycerol that does eventually appear in host lipid may have been respired to /sup 14/CO/sub 2/ then photosynthetically fixed by the zooxanthellae and synthesized into lipid fatty acid. The isolated zooxanthellae of C. gigantea contained 3.62 +/- 0.33 mM glycerol, which was 26x the 0.141 +/- 0.02 mM found in the coelenterate tissue. Aposymbiotic coelenterate tissue contained 0.169 +/- 0.05 mM glycerol. The metabolic inhibitors, sodium cyanide, aminooxyacetic acid and cerulenin were used to try and uncouple the production of glycerol by the zooxanthellae from its utilization by the coelenterate host. 10/sup -5/ M NaCN increased the ratio of cross photosynthesis to respiration in both intact tentacles and isolated zooxanthellae, increased translocation from 17.7 +/- 3.5% of total fixed carbon in controls to 43.5 +/- 5.79%, and doubled the amount of photosynthetically fixed carbon accumulating in the coelenterate host over that in controls.« less

Membrane anchoring γ-secretase modulators with terpene-derived moieties.

PubMed

Naumann, Eva Christine; Göring, Stefan; Ogorek, Isabella; Weggen, Sascha; Schmidt, Boris

2013-07-01

Modulation of γ-secretase activity is a promising therapeutic strategy for the treatment of Alzheimer's disease. Herein we report on the synthesis of carprofen- and tocopherol-derived small-molecule modulators carrying terpene moieties as lipophilic membrane anchors. Additionally, these modulators are equipped with an acidic moiety, which contributes to the desired modulatory effect on the γ-secretase with decreased formation of Aβ42 and increased Aβ38 production. Copyright © 2013 Elsevier Ltd. All rights reserved.

Studies on the defect underlying the lysosomal storage of sialic acid in Salla disease. Lysosomal accumulation of sialic acid formed from N-acetyl-mannosamine or derived from low density lipoprotein in cultured mutant fibroblasts.

PubMed Central

Renlund, M; Kovanen, P T; Raivio, K O; Aula, P; Gahmberg, C G; Ehnholm, C

1986-01-01

Salla disease is a lysosomal storage disorder characterized by mental retardation and disturbed sialic acid metabolism. To study endogenous synthesis and breakdown of sialic acid, fibroblasts were incubated for 5 d in the presence and then in the absence of N-[3H]acetylmannosamine. Labeling of free sialic acid was 5-10 times higher in mutant than in normal cells. Radioactivity decreased in 4 d by 75% in normal but only by 30% in mutant fibroblasts. The labeling pattern was not normalized upon coculture of mutant and normal cells. To study the metabolism of extracellular sialic acid, low-density lipoprotein (LDL) was labeled in the sialic acid moiety (periodate-NaB3H4) or in the protein moiety (125I). Binding, internalization, lysosomal degradation, and exit of products of protein catabolism were similar in normal and mutant fibroblasts. Upon incubation with LDL labeled in the sialic acid moiety, mutant cells accumulated 2-3 times more free sialic acid radioactivity than normal fibroblasts, mostly in the lysosomal fraction. After a 24-h chase incubation, radioactivity in free sialic acid decreased by 70-80% in normal but only by 10-30% in mutant cells. In mutant fibroblasts, 40% of the radioactivity remained in lysosomes, whereas no labeled free sialic acid was detected in lysosomes from normal fibroblasts. We conclude that in Salla disease, fibroblast endogenous synthesis of sialic acid and lysosomal cleavage of exogenous glycoconjugates is normal, but free sialic acid cannot leave the lysosome. These findings suggest that the basic defect in Salla disease is deficient transport of free sialic acid through the lysosomal membrane. PMID:3944269

Synthetic substrates for enzyme analysis

DOEpatents

Bissell, E.R.; Mitchell, A.R.; Pearson, K.W.; Smith, R.E.

1983-06-14

Synthetic substrates are provided which may be represented as A-D. The A moiety includes an amino acid, polypeptide, or derivative. The D moiety includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons. No Drawings

Synthetic substrates for enzyme analysis

DOEpatents

Bissell, Eugene R.; Mitchell, Alexander R.; Pearson, Karen W.; Smith, Robert E.

1983-01-01

Synthetic substrates are provided which may be represented as A-D. The A moiety thereof includes an amino acid, polypeptide, or derivative thereof. The D moiety thereof includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons.

Toxicology of Perfluoroalkyl Acids*

EPA Science Inventory

The perfluoroalkyl acids (PFAAs) are a family of organic chemicals consisting of a perfluorinated carbon backbone (4-12 in length) and an acidic functional moiety (carboxylate or sulfonate). These compounds are chemically stable, have excellent surface-tension reducing properties...

Structure characterization of lipocyclopeptide antibiotics, aspartocins A, B & C, by ESI-MSMS and ESI-nozzle-skimmer-MSMS.

PubMed

Siegel, Marshall M; Kong, Fangming; Feng, Xidong; Carter, Guy T

2009-12-01

Three lipocyclopeptide antibiotics, aspartocins A (1), B (2), and C (3), were obtained from the aspartocin complex by HPLC separation methodology. Their structures were elucidated using previously published chemical degradation results coupled with spectroscopic studies including ESI-MS, ESI-Nozzle Skimmer-MSMS and NMR. All three aspartocin compounds share the same cyclic decapeptide core of cyclo [Dab2 (Asp1-FA)-Pip3-MeAsp4-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11]. They differ only in the fatty acid side chain moiety (FA) corresponding to (Z)-13-methyltetradec-3-ene-carbonyl, (+,Z)-12-methyltetradec-3-ene-carbonyl and (Z)-12-methyltridec-3-ene-carbonyl for aspartocins A (1), B (2), and C (3), respectively. All of the sequence ions were observed by ESI-MSMS of the doubly charged parent ions. However, a number of the sequence ions observed were of low abundance. To fully sequence the lipocyclopeptide antibiotic structures, these low abundance sequence ions together with complementary sequence ions were confirmed by ESI-Nozzle-Skimmer-MSMS of the singly charged linear peptide parent fragment ions H-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11-Dab2(1+)-Asp1-FA. Cyclization of the aspartocins was demonstrated to occur via the beta-amino group of Dab2 from ions of moderate intensity in the ESI-MSMS spectra. As the fatty acid moieties do not undergo internal fragmentations under the experimental ESI mass spectral conditions used, the 14 Da mass difference between the fatty acid moieties of aspartocins A (1) and B (2) versus aspartocin C (3) was used as an internal mass tag to differentiate fragment ions containing fatty acid moieties and those not containing the fatty acid moieties. The most numerous and abundant fragment ions observed in the tandem mass spectra are due to the cleavage of the tertiary nitrogen amide of the pipecolic acid residue-3 (16 fragment ions) and the proline residue-11 (7 fragment ions). In addition, the neutral loss of ethanimine from alpha,beta-diaminobutyric acid residue 9 was observed for the parent molecular ion and for 7 fragment ions. Copyright 2009 John Wiley & Sons, Ltd.

Biosynthetic Origin of Hygromycin A

PubMed Central

Habib, El-Sayed E.; Scarsdale, J. Neel; Reynolds, Kevin A.

2003-01-01

Hygromycin A, an antibiotic produced by Streptomyces hygroscopicus, is an inhibitor of bacterial ribosomal peptidyl transferase. The antibiotic binds to the ribosome in a distinct but overlapping manner with other antibiotics and offers a different template for generation of new agents effective against multidrug-resistant pathogens. Reported herein are the results from a series of stable-isotope-incorporation studies demonstrating the biosynthetic origins of the three distinct structural moieties which comprise hygromycin A. Incorporation of [1-13C]mannose and intact incorporation of d-[1,2-13C2]glucose into the 6-deoxy-5-keto-d-arabino-hexofuranose moiety are consistent with a pathway in which mannose is converted to an activated l-fucose, via a 4-keto-6-deoxy-d-mannose intermediate, with a subsequent unusual mutation of the pyranose to the corresponding furanose. The aminocyclitol moiety was labeled by d-[1,2-13C2]glucose in a manner consistent with formation of myo-inositol and a subsequent unprecedented oxidation and transamination of the C-2 hydroxyl group to generate neo-inosamine-2. Incorporation of [carboxy-13C]-4-hydroxybenzoic acid and intact incorporation of [2,3-13C2]propionate are consistent with a polyketide synthase-type decarboxylation condensation to generate the 3,4-dihydroxy-α-methylcinnamic acid moiety of hygromycin A. No labeling of hygromycin A was observed when [3-13C]tyrosine, [3-13C]phenylalanine, or [carboxy-13C]benzoic acid was used, suggesting that the 4-hydroxybenzoic acid is derived directly from chorismic acid. Consistent with this hypothesis was the observation that hygromycin A titers could be reduced by addition of N-(phosphonomethyl)-glycine (an inhibitor of chorismic acid biosynthesis) and restored by coaddition of 4-hydroxybenzoic acid. The convergent biosynthetic pathway established for hygromycin A offers significant versatility for applying the techniques of combinatorial and directed biosynthesis to production of new antibiotics which target the ribosomal peptidyl transferase activity. PMID:12821448

Red Clover HCT2, a Hydroxycinnamoyl-Coenzyme A:Malate Hydroxycinnamoyl Transferase, Plays a Crucial Role in Biosynthesis of Phaselic Acid and Other Hydroxycinnamoyl-Malate Esters in Vivo1[OA

PubMed Central

Sullivan, Michael L.; Zarnowski, Robert

2011-01-01

In red clover (Trifolium pratense) leaves, phaselic acid (2-O-caffeoyl-l-malate) accumulates to several mmol kg−1 fresh weight and is a crucial component of a natural system that prevents protein breakdown during harvest and storage of this forage crop. Previously, we identified HCT2, a red clover gene encoding a hydroxycinnamoyl-Coenzyme A (CoA) hydroxycinnamoyl transferase capable of transferring p-coumaroyl and caffeoyl moieties from their CoA derivatives to malic acid to form the corresponding hydroxycinnamoyl-malate esters in vitro. Here, we carried out a detailed kinetic analysis of the enzyme and examined its in vivo function in red clover via reverse genetics. The kinetic analysis indicates that in vitro, despite similar Km values for the tested hydroxycinnamoyl-CoA derivatives, HCT2 favors transfer to malate of p-coumaroyl and feruloyl moieties over caffeoyl moieties by greater than 5-fold. Reverse reaction (transfer of hydroxycinnamoyl moieties from malate to CoA) by HCT2 was observed with p-coumaroyl-malate but not phaselic acid. Analysis of red clover plants down-regulated for HCT2 expression via RNA interference showed a significant and substantial correlation between HCT2 mRNA levels and phaselic acid accumulation (P < 0.005). In several of the HCT2-silenced plants, phaselic acid and p-coumaroyl-malate levels were reduced to <5% that of wild-type controls. These reductions resulted in easily observable phenotypes including reduced polyphenol oxidase-mediated browning and a reduction in blue epidermal fluorescence under ultraviolet light. These results demonstrate a crucial role for HCT2 in phaselic acid accumulation in red clover and define a previously undescribed pathway for the biosynthesis of hydroxycinnamoyl-malate esters in plants. PMID:21205620

Toxicology of Perfluoroalkyl acids

EPA Science Inventory

The Perfluoroalkyl acids(PFAAs) area a family of organic chemicals consisting of a perflurinated carbon backbone (4-12in length) and a acidic functional moiety (Carboxylate or sulfonate). These compounds have excellent surface-tension reducing properties and have numerous industr...

Caffeoyl triterpenes from pear (Pyrus pyrifolia Nakai) fruit peels and their antioxidative activities against oxidation of rat blood plasma.

PubMed

Cho, Jeong-Yong; Kim, Chan Mi; Lee, Hyoung Jae; Lee, Sang-Hyun; Cho, Jeong-An; Kim, Wol-Soo; Park, Keun-Hyung; Moon, Jae-Hak

2013-05-15

Six triterpenes, including three caffeoyl triterpenes, were purified and isolated from pear fruit ( Pyrus pyrifolia Nakai cv. Chuwhangbae) peel extracts using various column chromatography techniques with a guided 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging assay. The isolated compounds were identified as betulinic aldehyde (1), lupeol (2), betulinic acid (3), 3-O-cis-caffeoylbetulinic acid (4), 3-O-trans-caffeoylbetulinic acid (5), and 3-O-trans-caffeoyloleanolic acid (6) on the basis of nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. Four compounds (1, 4-6) were identified from Asian pear fruit for the first time. In addition, compounds 4-6, containing a caffeic acid moiety, showed higher DPPH radical-scavenging and suppression effects against copper ion-induced oxidation of rat blood plasma than other compounds without a caffeic acid moiety.

Redox regulation of protein tyrosine phosphatase 1B (PTP1B): Importance of steric and electronic effects on the unusual cyclization of the sulfenic acid intermediate to a sulfenyl amide

NASA Astrophysics Data System (ADS)

Sarma, Bani Kanta

2013-09-01

The redox regulation of protein tyrosine phosphatase 1B (PTP1B) via the unusual transformation of its sulfenic acid (PTP1B-SOH) to a cyclic sulfenyl amide intermediate is studied by using small molecule chemical models. These studies suggest that the sulfenic acids derived from the H2O2-mediated reactions o-amido thiophenols do not efficiently cyclize to sulfenyl amides and the sulfenic acids produced in situ can be trapped by using methyl iodide. Theoretical calculations suggest that the most stable conformer of such sulfenic acids are stabilized by nO → σ*S-OH orbital interactions, which force the -OH group to adopt a position trans to the S⋯O interaction, leading to an almost linear arrangement of the O⋯S-O moiety and this may be the reason for the slow cyclization of such sulfenic acids to their corresponding sulfenyl amides. On the other hand, additional substituents at the 6-position of o-amido phenylsulfenic acids that can induce steric environment and alter the electronic properties around the sulfenic acid moiety by S⋯N or S⋯O nonbonded interactions destabilize the sulfenic acids by inducing strain in the molecule. This may lead to efficient the cyclization of such sulfenic acids. This model study suggests that the amino acid residues in the close proximity of the sulfenic acid moiety in PTP1B may play an important role in the cyclization of PTP1B-SOH to produce the corresponding sulfenyl amide.

The occurrence of triglycerides in Namibian Shelf diatomaceous ooze

NASA Astrophysics Data System (ADS)

Boon, Jaap J.; Irene, W.; Rijpstra, C.; de Leeuw, J. W.; Burlingame, A. L.

1980-01-01

The triglyceride fraction, isolated from extractable lipids of a diatomaceous ooze off shore Walvis Bay (S.W. Africa) by TLC methods, was analyzed by direct probe low and high resolution mass spectrometry. The mass spectral data reveal the fatty acid moieties and their relative distribution in the triglycerides identified. The C 12, C 14, C 15 and C 16 are the major composing fatty acid moieties. The triglycerides are thought to be present in protective structures such as diatom spores, which were found to be present by scanning electron microscopy.

Click strategy using disodium salts of amino acids improves the water solubility of plinabulin and KPU-300.

PubMed

Yakushiji, Fumika; Muguruma, Kyohei; Hayashi, Yoshiki; Shirasaka, Takuya; Kawamata, Ryosuke; Tanaka, Hironari; Yoshiwaka, Yushi; Taguchi, Akihiro; Takayama, Kentaro; Hayashi, Yoshio

2017-07-15

Plinabulin and KPU-300 are promising anti-microtubule agents; however, the low water solubility of these compounds (<0.1µg/mL) has limited their pharmaceutical advantages. Here, we developed five water-soluble derivatives of plinabulin and KPU-300 with a click strategy using disodium salts of amino acids. The mother skeleton, diketopiperazine (DKP), was transformed into a monolactim-type alkyne and a copper-catalyzed alkyne azide cycloaddition (CuAAC) combined azides that was derived from amino acids as a water-solubilizing moiety. The conversion of carboxyl groups into disodium salts greatly improved the water solubility by 0.8 million times compared to the solubility of the parent molecules. In addition, the α-amino acid side chains of the water-solubilizing moieties affected both the water solubility and the half-lives of the compounds during enzymatic hydrolysis. Our effort to develop a variety of water-soluble derivatives using the click strategy has revealed that the replaceable water-solubilizing moieties can alter molecular solubility and stability under enzymatic hydrolysis. With this flexibility, we are approaching to the in vivo study using water-soluble derivative. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phosphine-free Stille-Migita chemistry for the mild and orthogonal modification of DNA and RNA.

PubMed

Krause, André; Hertl, Alexander; Muttach, Fabian; Jäschke, Andres

2014-12-08

An optimized catalyst system of [Pd2 (dba)3 ] and AsPh3 efficiently catalyzes the Stille reaction between a diverse set of functionalized stannanes and halogenated mono-, di- and oligonucleotides. The methodology allows for the facile conjugation of short and long nucleic acid molecules with moieties that are not compatible with conventional chemical or enzymatic synthesis, among them acid-, base-, or fluoride-labile protecting groups, fluorogenic and synthetically challenging moieties with good to near-quantitative yields. Notably, even azides can be directly introduced into oligonucleotides and (deoxy)nucleoside triphosphates, thereby giving direct access to "clickable" nucleic acids. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fast and Facile Synthesis of 4-Nitrophenyl 2-Azidoethylcarbamate Derivatives from N-Fmoc-Protected α-Amino Acids as Activated Building Blocks for Urea Moiety-Containing Compound Library.

PubMed

Chen, Ying-Ying; Chang, Li-Te; Chen, Hung-Wei; Yang, Chia-Ying; Hsin, Ling-Wei

2017-03-13

A fast and facile synthesis of a series of 4-nitrophenyl 2-azidoethylcarbamate derivatives as activated urea building blocks was developed. The N-Fmoc-protected 2-aminoethyl mesylates derived from various commercially available N-Fmoc-protected α-amino acids, including those having functionalized side chains with acid-labile protective groups, were directly transformed into 4-nitrophenyl 2-azidoethylcarbamate derivatives in 1 h via a one-pot two-step reaction. These urea building blocks were utilized for the preparation of a series of urea moiety-containing mitoxantrone-amino acid conjugates in 75-92% yields and parallel solution-phase synthesis of a urea compound library consisted of 30 members in 38-70% total yields.

Lipid-peptide-polymer conjugates and nanoparticles thereof

DOEpatents

Xu, Ting; Dong, He; Shu, Jessica

2015-06-02

The present invention provides a conjugate having a peptide with from about 10 to about 100 amino acids, wherein the peptide adopts a helical structure. The conjugate also includes a first polymer covalently linked to the peptide, and a hydrophobic moiety covalently linked to the N-terminus of the peptide, wherein the hydrophobic moiety comprises a second polymer or a lipid moiety. The present invention also provides helix bundles form by self-assembling the conjugates, and particles formed by self-assembling the helix bundles. Methods of preparing the helix bundles and particles are also provided.

High performance, durable polymers including poly(phenylene)

DOEpatents

Fujimoto, Cy; Pratt, Harry; Anderson, Travis Mark

2017-02-28

The present invention relates to functionalized polymers including a poly(phenylene) structure. In some embodiments, the polymers and copolymers of the invention include a highly localized concentration of acidic moieties, which facilitate proton transport and conduction through networks formed from these polymers. In addition, the polymers can include functional moieties, such as electron-withdrawing moieties, to protect the polymeric backbone, thereby extending its durability. Such enhanced proton transport and durability can be beneficial for any high performance platform that employs proton exchange polymeric membranes, such as in fuel cells or flow batteries.

Sorption mechanism of enrofloxacin on humic acids extracted from Brazilian soils.

PubMed

Martínez-Mejía, Mónica J; Sato, Isabela; Rath, Susanne

2017-07-01

Veterinary antimicrobials are emerging environmental contaminants of concern. In this study, the sorption of enrofloxacin (ENR) onto humic acids (HAs) extracted from three Brazilian soils was evaluated. HAs were characterized by elemental analysis and solid 13 C nuclear magnetic resonance spectroscopy. The sorption of ENR onto HAs was at least 20-fold higher than onto the soils from which they were separated. Ionic and cation bridging are the primary interactions involved. The interactions driven by cation exchange are predominant on HAs, which appear to have abundant carboxylic groups and a relatively high proportion of H-bond donor moieties with carbohydrate-like structures. Interactions explained by cation bridging and/or surface complexation on HAs are facilitated by moieties containing conjugated ligands, significant content of oxygen-containing functional groups, such as phenolic-OH or lignin-like structures. HAs containing electron-donating phenolic moieties and carboxylic acid ligand groups exhibit a sorption mechanism that is primarily driven by strong metal binding, favoring the formation of ternary complexes between functional groups of the organic matter and drugs.

Spectral and thermal study of the ternary complexes of nickel with sulfasalazine and some amino acids

NASA Astrophysics Data System (ADS)

Soliman, Ahmed A.

2006-12-01

The ternary complexes of Ni(II) with sulfasalazine (H 3SS) as a primary ligand and alanine (ala), aspartic acid (asp), histidene (hist), methionine (meth) and serine (ser) amino acids as secondary ligands have been synthesized. Characterization of the complexes was based on elemental analyses, IR, UV-vis, mass spectra, magnetic moment and thermal analysis (TG). The isolated complexes were found to have the general formula [M(HSS)(AA)]4H 2O (AA = ala, asp, hist, meth, or ser amino acid) where nickel is tetra-coordinated. The thermal stability of the complexes was studied and the weight losses for the decomposition of the complexes were calculated and correlated with the mass fragmentation pattern. In most cases, the amino acid moiety is removed along with the Schiff base moiety leaving NiO as a metallic residue. The metallic residue was confirmed by powder XRD measurements.

Binary Supramolecular Gel of Achiral Azobenzene with a Chaperone Gelator: Chirality Transfer, Tuned Morphology, and Chiroptical Property.

PubMed

Ji, Lukang; Ouyang, Guanghui; Liu, Minghua

2017-10-31

Binary supramolecular gels based on achiral azobenzene derivatives and a chiral chaperone gelator, long-alkyl-chain-substituted L-Histidine (abbreviated as LHC18) that could assist many nongelling acids in forming gels, were investigated in order to fabricate the chiroptical gel materials in a simple way. It was found that although the carboxylic acid-terminated achiral azobenzene derivatives could not form gels in any solvents, when mixed with LHC18 they formed the co-gels and self-assembled into various morphologies ranging from nanotubes and loose nanotubes to nanosheets, depending on the substituent groups on the azobenzene moiety. The ether linkage and the number of carboxylic acid groups attached to the azobenzene moiety played important roles. Upon gel formation, the localized molecular chirality in LHC18 could be transferred to the azobenzene moiety. Combined with the trans-cis isomerization of the azobenzene, optically and chiroptically reversible gels were generated. It was found that the gel based on azobenzene with two carboxylic acid groups and ether linkages showed clear optical reversibility but less chiroptical reversibility, whereas the gel based on azobenzene with one carboxylic acid and an ether linkage showed both optical and chiroptical reversibility. Thus, new insights into the relationship among the molecular structures of the azobenzene, self-assembled nanostructures in the gel and the optical and chiroptical reversibility were disclosed.

Integrating metabolomics and transcriptomics data to discover a biocatalyst that can generate the amine precursors for alkamide biosynthesis

PubMed Central

Rizhsky, Ludmila; Jin, Huanan; Shepard, Michael R.; Scott, Harry W.; Teitgen, Alicen M.; Perera, M. Ann; Mhaske, Vandana; Jose, Adarsh; Zheng, Xiaobin; Crispin, Matt; Wurtele, Eve S.; Jones, Dallas; Hur, Manhoi; Góngora-Castillo, Elsa; Buell, C. Robin; Minto, Robert E.; Nikolau, Basil J.

2016-01-01

Summary The Echinacea genus is exemplary of over 30 plant families that produce a set of bioactive amides, called alkamides. The Echinacea alkamides may be assembled from two distinct moieties, a branched-chain amine that is acylated with a novel polyunsaturated fatty acid. In this study we identified the potential enzymological source of the amine moiety as a pyridoxal phosphate dependent decarboxylating enzyme that uses branched chain amino acids as substrate. This identification was based on a correlative analysis of the transcriptomes and metabolomes of 36 different E. purpurea tissues and organs, which expressed distinct alkamide profiles. Although no correlation was found between the accumulation patterns of the alkamides and their putative metabolic precursors (i.e., fatty acids and branched chain amino acids), isotope-labeling analyses supported the transformation of valine and isoleucine to isobutylamine and 2-methylbutylamine as reactions of alkamide biosynthesis. Sequence homology identified the pyridoxal phosphate dependent decarboxylase-like proteins in the translated proteome of E. purpurea. These sequences were prioritized for direct characterization by correlating their transcript levels with alkamide accumulation patterns in different organs and tissues, and this multi-pronged approach led to the identification and characterization of a branched-chain amino acid decarboxylase, which would appear to be responsible for generating the amine moieties of naturally occurring alkamides. PMID:27497272

Selective coupling of methotrexate to peptide hormone carriers through a gamma-carboxamide linkage of its glutamic acid moiety: benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate activation in salt coupling.

PubMed Central

Nagy, A; Szoke, B; Schally, A V

1993-01-01

A convenient synthetic method is described for the preparation of peptide-methotrexate (MTX) conjugates in which MTX is coupled selectively through the gamma-carboxyl group of its glutamic acid moiety to a free amino group in peptide analogs. The syntheses of a somatostatin analog-MTX conjugate (MTX-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2) (AN-51) and two conjugates of analogs of luteinizing hormone-releasing hormone (LH-RH) with MTX [Glp-His-Trp-Ser-Tyr-D-Lys(MTX)-Leu-Arg-Pro-Gly-NH2] (AJ-04) and [Ac-Ser-Tyr-D-Lys(MTX)-Leu-Arg-Pro-NH-Et] AJ-51 are presented as examples. Benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent) was used in the synthesis for activation of 4-amino-4-deoxy-N10-methylpteroic acid, which reacted with the potassium salt of glutamic acid alpha-tert-butyl ester in dimethyl sulfoxide to form the suitably protected MTX derivative. This synthesis provides an example of the high suitability of BOP reagent for the salt-coupling method. The selectively protected MTX derivative was then coupled to the different peptide carriers and deprotected under relatively mild conditions by trifluoroacetic acid. The conjugates of MTX with hormonal analogs are suitable for targeting to various tumors that possess receptors for the peptide moieties. PMID:8101004

Multifunctional mesoporous silica catalyst

DOEpatents

Lin, Victor Shang-Yi; Tsai, Chih-Hsiang; Chen, Hung-Ting; Pruski, Marek; Kobayashi, Takeshi

2015-03-31

The present invention provides bifunctional silica mesoporous materials, including mesoporous silica nanoparticles ("MSN"), having pores modified with diarylammonium triflate and perfluoroaryl moieties, that are useful for the acid-catalyzed esterification of organic acids with organic alcohols.

Oleanane-type triterpene saponins from Calendula stellata.

PubMed

Lehbili, Meryem; Alabdul Magid, Abdulmagid; Kabouche, Ahmed; Voutquenne-Nazabadioko, Laurence; Abedini, Amin; Morjani, Hamid; Sarazin, Thomas; Gangloff, Sophie C; Kabouche, Zahia

2017-12-01

Five previously undescribed bisdesmosidic triterpenoid saponins named calendustellatosides A-E, along with fifteen known compounds were isolated from the 70% ethanol whole plant extract of Calendula stellata Cav. (Asteraceae). Their structures were determined by 1D- and 2D-NMR spectroscopy as well as high resolution mass spectrometry and acid hydrolysis. The saponins comprised oleanolic acid, echinocystic acid, morolic acid or mesembryanthemoidigenic acid as the aglycones and saccharide moieties at C-3 and C-28. Like most Calendula saponins, the sugar moiety linked at C-3 was either β-d-glucose or β-d-glucuronic acid which could be substituted at C-3 by a β-d-galactose and/or C-2 by a supplementary β-d-galactose or a β-d-glucose. The sugar moiety linked to C-28 was determined as β-d-glucose. The antibacterial evaluation of compounds 1-20 by bioautography on Staphylococcus aureus followed by the determination of MIC values of active compounds by serial dilution technique against 5 bacteria revealed that; calendustellatoside D was the most active against Enterococcus faecalis with an antibacterial effect comparable to antibiotics. The cytotoxic activities of isolated compounds were evaluated against fibrosarcoma cell line (HT1080) and human lung cancer cell line (A549). Calendustellatosides B and D exhibited a low cytotoxic activity against HT1080 cell line with IC 50 values of 47 ± 0.6 and 39 ± 0.5 μM, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Theoretical study of the thermodynamics of the mechanisms underlying antiradical activity of cinnamic acid derivatives.

PubMed

Amić, Ana; Marković, Zoran; Klein, Erik; Dimitrić Marković, Jasmina M; Milenković, Dejan

2018-04-25

The role of antiradical moieties (catechol, guaiacyl and carboxyl group) and molecular conformation in antioxidative potency of dihydrocaffeic acid (DHCA) and dihydroferulic acid (DHFA) was investigated by density functional theory (DFT) method. The thermodynamic preference of different reaction paths of double (2H + /2e - ) free radical scavenging mechanisms was estimated. Antiradical potency of DHCA and DHFA was compared with that exerted by their unsaturated analogs - caffeic acid (CA) and ferulic acid (FA). Cis/trans and anti-isomers of studied cinnamic acid derivatives may scavenge free radicals via double processes by involvement of catechol or guaiacyl moiety. Carboxyl group of syn-isomers may also participate in the inactivation of free radicals. Gibbs free energies of reactions with various free radicals indicate that syn-DHCA and syn-DHFA, colon catabolites that could be present in systemic circulation in low μM concentrations, have a potential to contribute to health benefits by direct free radical scavenging. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of N-difluoromethyl-1,2-dihydropyrid-2-one acetic acid regioisomers: dual inhibitors of cyclooxygenases and 5-lipoxygenase.

PubMed

Yu, Gang; Praveen Rao, P N; Chowdhury, Morshed A; Abdellatif, Khaled R A; Dong, Ying; Das, Dipankar; Velázquez, Carlos A; Suresh, Mavanur R; Knaus, Edward E

2010-04-01

A new group of acetic acid (7a-c, R(1) = H), and propionic acid (7d-f, R(1) = Me), regioisomers wherein a N-difluoromethyl-1,2-dihydropyrid-2-one moiety is attached via its C-3, C-4, and C-5 position was synthesized. This group of compounds exhibited a more potent inhibition, and hence selectivity, for the cyclooxygenase-2 (COX-2) relative to the COX-1 isozyme. Attachment of the N-difluoromethyl-1,2-dihydropyrid-2-one ring system to an acetic acid, or propionic acid, moiety confers potent 5-LOX inhibitory activity, that is, absent in traditional arylacetic acid NSAIDs. 2-(1-Difluoromethyl-2-oxo-1,2-dihydropyridin-5-yl)acetic acid (7c) exhibited the best combination of dual COX-2 and 5-LOX inhibitory activities. Molecular modeling (docking) studies showed that the highly electronegative CHF(2) substituent present in 7c, that showed a modest selectivity for the COX-2 isozyme, is oriented within the secondary pocket (Val523) present in COX-2 similar to the sulfonamide (SO(2)NH(2)) COX-2 pharmacophore present in celecoxib, and that the N-difluoromethyl-1,2-dihydropyrid-2-one pharmacophore is oriented close to the region containing the LOX enzyme catalytic iron (His361, His366, and His545). Accordingly, the N-difluoromethyl-1,2-dihyrdopyrid-2-one moiety possesses properties suitable for the design of dual COX-2/5-LOX inhibitory drugs. 2010 Elsevier Ltd. All rights reserved.

Neuraminidase inhibition of Dietary chlorogenic acids and derivatives - potential antivirals from dietary sources.

PubMed

Gamaleldin Elsadig Karar, Mohamed; Matei, Marius-Febi; Jaiswal, Rakesh; Illenberger, Susanne; Kuhnert, Nikolai

2016-04-01

Plants rich in chlorogenic acids (CGAs), caffeic acids and their derivatives have been found to exert antiviral effects against influenza virus neuroaminidase. In this study several dietary naturally occurring chlorogenic acids, phenolic acids and derivatives were screened for their inhibitory activity against neuroaminidases (NAs) from C. perfringens, H5N1 and recombinant H5N1 (N-His)-Tag using a fluorometric assay. There was no significant difference in inhibition between the different NA enzymes. The enzyme inhibition results indicated that chlorogenic acids and selected derivatives, exhibited high activities against NAs. It seems that the catechol group from caffeic acid was important for the activity. Dietary CGA therefore show promise as potential antiviral agents. However, caffeoyl quinic acids show low bioavailibility and are intensly metabolized by the gut micro flora, only low nM concentrations are observed in plasma and urine, therefore a systemic antiviral effect of these compounds is unlikely. Nevertheless, gut floral metabolites with a catechol moiety or structurally related dietary phenolics with a catechol moiety might serve as interesting compounds for future investigations.

Triterpenoidal saponins from the fruits of Gleditsia caspica with proapoptotic properties.

PubMed

Shaheen, Usama; Ragab, Ehab A; Abdalla, Ashraf N; Bader, Ammar

2018-01-01

Three previously undescribed oleanane-type triterpenoidal saponins named caspicaosides L-N were isolated from the fruits of Gleditsia caspica Desf. The aglycons of these saponins were echinocystic acid, erythrodiol and 12-oleanene-3,28,30-triol. Caspicaoside L is a bisdesmosidic saponin acylated with two monoterpenic acids. It has a disaccharide moiety made up of glucose and arabinose attached to C-3 and pentasaccharide moiety linked to C-28 made up of one glucose, 2 xyloses, one inner rhamnose and one terminal rhamnose which was acylated with two identical monoterpenic acids. Caspicaoside M is a monodesmosidic saponin with a trisaccharide moiety at C-3 made up of glucose, xylose and arabinose, while caspicaoside N has a disaccharide moiety at C-3 made up of glucose and arabinose. Their structures were determined by extensive 1D and 2D (DQF-COSY, HSQC, TOCSY, 1 H- 13 C-HSQC-TOCSY, HMBC, ROESY, NOESY) NMR, HRESIMS analyses and chemical degradation. The cytotoxicity MTT-based assay showed that caspicaosides M, N and L, respectively, exhibited high cytotoxic activity with IC 50  ≤ 10 μM (72 h) at least against one of the three used cancer cell lines, MCF 7, A2780 and HT 29; and were 2-34 folds selective against the normal fibroblasts (MRC 5). All compounds also induced apoptosis and caused G 2 /M arrest in MCF 7 cells (24 h); thus showing pro-apoptotic properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spithioneines A and B, Two New Bohemamine Derivatives Possessing Ergothioneine Moiety from a Marine-Derived Streptomyces spinoverrucosus

PubMed Central

2015-01-01

Spithioneines A and B (1 and 2), two new bohemamine-type pyrrolizidine alkaloids possessing an unusual ergothioneine moiety, were isolated from a marine-derived Streptomyces spinoverrucosus. Their structures were elucidated by spectroscopic analysis, CD spectra, and chemical degradation and synthesis. Compounds 1 and 2 are rare natural products that incorporate the amino acid ergothioneine. PMID:26024315

Two pathways for pyrrole formation in coumermycin A(1) biosynthesis: the central pyrrole moiety is formed from L-threonine.

PubMed

Siebenberg, Stefanie; Burkard, Nadja; Knuplesch, Anna; Gust, Bertolt; Grond, Stephanie; Heide, Lutz

2011-11-25

Coumermycin A(1) is an aminocoumarin antibiotic produced by Streptomyces rishiriensis. It contains three pyrrole rings, that is, two terminal 5-methyl-pyrrole-2-carboxyl moieties and a central 3-methylpyrrole-2,4-dicarboxylic acid moiety. The biosynthesis of the terminal pyrrole moieties has been elucidated previously. However, the biosynthetic precursors of the central pyrrole moiety have remained unknown, and none of the genes or enzymes involved in its formation has been identified. We now show that five genes, contained in a contiguous 4.7 kb region within the coumermycin biosynthetic gene cluster, are required for the biosynthesis of this central pyrrole moiety. Each of these genes was deleted individually, resulting in a strong reduction or an abolishment of coumermycin production. External feeding of the central pyrrole moiety restored coumermycin production. One of these genes shows similarity to L-threonine kinase genes. Feeding of [U-(13)C,(15) N]L-threonine and (13)C NMR analysis of the resulting compound unequivocally proved that threonine was incorporated intact into the central pyrrole (19 % enrichment) to provide the heterocyclic nitrogen as well as four of the seven carbons of this moiety. Therefore, this pyrrole is formed via a new, hitherto unknown biosynthetic pathway. A hypothesis for the reaction sequence leading to the central pyrrole moiety of coumermycin A(1) is presented. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Flagellar glycosylation in Clostridium botulinum.

PubMed

Twine, Susan M; Paul, Catherine J; Vinogradov, Evgeny; McNally, David J; Brisson, Jean-Robert; Mullen, James A; McMullin, David R; Jarrell, Harold C; Austin, John W; Kelly, John F; Logan, Susan M

2008-09-01

Flagellins from Clostridium botulinum were shown to be post-translationally modified with novel glycan moieties by top-down MS analysis of purified flagellin protein from strains of various toxin serotypes. Detailed analyses of flagellin from two strains of C. botulinum demonstrated that the protein is modified by a novel glycan moiety of mass 417 Da in O-linkage. Bioinformatic analysis of available C. botulinum genomes identified a flagellar glycosylation island containing homologs of genes recently identified in Campylobacter coli that have been shown to be responsible for the biosynthesis of legionaminic acid derivatives. Structural characterization of the carbohydrate moiety was completed utilizing both MS and NMR spectroscopy, and it was shown to be a novel legionaminic acid derivative, 7-acetamido-5-(N-methyl-glutam-4-yl)-amino-3,5,7,9-tetradeoxy-D-glycero-alpha-D-galacto-nonulosonic acid, (alphaLeg5GluNMe7Ac). Electron transfer dissociation MS with and without collision-activated dissociation was utilized to map seven sites of O-linked glycosylation, eliminating the need for chemical derivatization of tryptic peptides prior to analysis. Marker ions for novel glycans, as well as a unique C-terminal flagellin peptide marker ion, were identified in a top-down analysis of the intact protein. These ions have the potential for use in for rapid detection and discrimination of C. botulinum cells, indicating botulinum neurotoxin contamination. This is the first report of glycosylation of Gram-positive flagellar proteins by the 'sialic acid-like' nonulosonate sugar, legionaminic acid.

Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of Carboxylic Acids

PubMed Central

2011-01-01

Antagonism of the CRTH2 receptor represents a very attractive target for a variety of allergic diseases. Most CRTH2 antagonists known to date possess a carboxylic acid moiety, which is essential for binding. However, potential acid metabolites O-acyl glucuronides might be linked to idiosynchratic toxicity in humans. In this communication, we describe a new series of compounds that lack the carboxylic acid moiety. Compounds with high affinity (Ki < 10 nM) for the receptor have been identified. Subsequent optimization succeeded in reducing the high metabolic clearance of the first compounds in human and rat liver microsomes. At the same time, inhibition of the CYP isoforms was optimized, giving rise to stable compounds with an acceptable CYP inhibition profile (IC50 CYP2C9 and 2C19 > 1 μM). Taken together, these data show that compounds devoid of carboxylic acid groups could represent an interesting alternative to current CRTH2 antagonists in development. PMID:24900284

Ion pair recognition by Zn-porphyrin/crown ether conjugates: visible sensing of sodium cyanide.

PubMed

Kim, Yeon-Hwan; Hong, Jong-In

2002-03-07

Synthesis and complexation behavior of ditopic neutral receptors composed of both a Lewis-acidic binding site (zinc porphyrin moiety) and a Lewis-basic binding site (crown ether moiety) are reported; the receptors bound only NaCN in a ditopic fashion with a color change, and in contrast other sodium salts bound to the receptors in a monotopic fashion without a color change.

Synthesis, computational, and spectroscopic analysis of tunable highly fluorescent BN-1,2-azaborine derivatives containing the N-BOH moiety.

PubMed

Saint-Louis, Carl Jacky; Shavnore, Renée N; McClinton, Caleb D C; Wilson, Julie A; Magill, Lacey L; Brown, Breanna M; Lamb, Robert W; Webster, Charles Edwin; Schrock, Alan K; Huggins, Michael T

2017-12-13

Nine new polycyclic aromatic BN-1,2-azaborine analogues containing the N-BOH moiety were synthesized using a convenient two-step, one-pot procedure. Characterization of the prepared compounds show the luminescence wavelength and the quantum yields of the azaborines were tunable by controlling the power and location of the donor and acceptor substituents on the chromophore. UV-visible spectroscopy and density functional theory (DFT) computations revealed that the addition of electron-donating moieties to the isoindolinone hemisphere raised the energy of the HOMO, resulting in the reduction of the HOMO-LUMO gap. The addition of an electron-accepting moiety to the isoindolinone hemisphere and an electron-donating group to the boronic acid hemisphere decreased the HOMO-LUMO gap considerably, leading to emission properties from partial intramolecular charge transfer (ICT) states. The combined effect of an acceptor on the isoindolinone side and a donor on the boronic acid side (strong acceptor-π-donor) gave the most red-shifted absorption. The polycyclic aromatic BN-1,2-azaborines emitted strong fluorescence in solution and in the solid-state with the largest red-shifted emission at 640 nm and a Stokes shift of Δλ = 218 nm, or Δν = 8070 cm -1 .

Perfluoroalkyl acids : Recent activities and research progress

EPA Science Inventory

The perfluoroalkyl acids (PFAAs) are a family of man-made fluorinated organic chemicals consisting of a carbon backbone typically of four to fourteen in length and a charged functional moiety (primarily carboxylate, sulfonate or phosphonate). The two most widely known PFAAs are ...

Comparative description of PFAA developmental toxicity: An update

EPA Science Inventory

The perfluoroalkyl acids (PFAAs) are a family of fluorocarbons consisting of a perfluorinated carbon tail (typically 4-12 carbons in length) and an acidic functional moiety, usually carboxylate or sulfonate. These compounds have excellent surface tension reducing properties and h...

Chlorogenic acid-arabinose hybrid domains in coffee melanoidins: Evidences from a model system.

PubMed

Moreira, Ana S P; Coimbra, Manuel A; Nunes, Fernando M; Passos, Cláudia P; Santos, Sónia A O; Silvestre, Armando J D; Silva, André M N; Rangel, Maria; Domingues, M Rosário M

2015-10-15

Arabinose from arabinogalactan side chains was hypothesized as a possible binding site for chlorogenic acids in coffee melanoidins. To investigate this hypothesis, a mixture of 5-O-caffeoylquinic acid (5-CQA), the most abundant chlorogenic acid in green coffee beans, and (α1 → 5)-L-arabinotriose, structurally related to arabinogalactan side chains, was submitted to dry thermal treatments. The compounds formed during thermal processing were identified by electrospray ionization mass spectrometry (ESI-MS) and characterized by tandem MS (ESI-MS(n)). Compounds composed by one or two CQAs covalently linked with pentose (Pent) residues (1-12) were identified, along with compounds bearing a sugar moiety but composed exclusively by the quinic or caffeic acid moiety of CQAs. The presence of isomers was demonstrated by liquid chromatography online coupled to ESI-MS and ESI-MS(n). Pent1-2CQA were identified in coffee samples. These results give evidence for a diversity of chlorogenic acid-arabinose hybrids formed during roasting, opening new perspectives for their identification in melanoidin structures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel Isoniazid cocrystals with aromatic carboxylic acids: Crystal engineering, spectroscopy and thermochemical investigations

NASA Astrophysics Data System (ADS)

Diniz, Luan F.; Souza, Matheus S.; Carvalho, Paulo S.; da Silva, Cecilia C. P.; D'Vries, Richard F.; Ellena, Javier

2018-02-01

Four novel cocrystals of the anti-tuberculosis drug Isoniazid (INH), including two polymorphs, with the aromatic carboxylic acids p-nitrobenzoic (PNBA), p-cyanobenzoic (PCNBA) and p-aminobenzoic (PABA) were rationally designed and synthesized by solvent evaporation. Aiming to explore the possible supramolecular synthons of this API, these cocrystals were fully characterized by X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR) and thermal (TGA, DSC, HSM) techniques. The cocrystal formation was found to be mainly driven by the synthons formed by the pyridine and hydrazide moieties. In both INH-PABA polymorphs, the COOH acid groups are H-bonded to pyridine and hydrazide groups giving rise to the acid⋯pyridine and acid⋯hydrazide heterosynthons. In INH-PNBA and INH-PCNBA cocrystals these acid groups are only related to the pyridine moiety. In addition to the structural study, supramolecular and Hirshfeld surface analysis were also performed based on the structural data. The cocrystals were identified from the FT-IR spectra and their thermal behaviors were studied by a combination of DSC, TGA and HSM techniques.

Chromatographic behaviour predicts the ability of potential nootropics to permeate the blood-brain barrier.

PubMed

Farsa, Oldřich

2013-01-01

The log BB parameter is the logarithm of the ratio of a compound's equilibrium concentrations in the brain tissue versus the blood plasma. This parameter is a useful descriptor in assessing the ability of a compound to permeate the blood-brain barrier. The aim of this study was to develop a Hansch-type linear regression QSAR model that correlates the parameter log BB and the retention time of drugs and other organic compounds on a reversed-phase HPLC containing an embedded amide moiety. The retention time was expressed by the capacity factor log k'. The second aim was to estimate the brain's absorption of 2-(azacycloalkyl)acetamidophenoxyacetic acids, which are analogues of piracetam, nefiracetam, and meclofenoxate. Notably, these acids may be novel nootropics. Two simple regression models that relate log BB and log k' were developed from an assay performed using a reversed-phase HPLC that contained an embedded amide moiety. Both the quadratic and linear models yielded statistical parameters comparable to previously published models of log BB dependence on various structural characteristics. The models predict that four members of the substituted phenoxyacetic acid series have a strong chance of permeating the barrier and being absorbed in the brain. The results of this study show that a reversed-phase HPLC system containing an embedded amide moiety is a functional in vitro surrogate of the blood-brain barrier. These results suggest that racetam-type nootropic drugs containing a carboxylic moiety could be more poorly absorbed than analogues devoid of the carboxyl group, especially if the compounds penetrate the barrier by a simple diffusion mechanism.

Hydroxyapatite-phosphonoformic acid hybrid compounds prepared by hydrothermal method

NASA Astrophysics Data System (ADS)

Turki, Thouraya; Othmani, Masseoud; Bantignies, Jean-Louis; Bouzouita, Khaled

2014-01-01

Hydroxyapatites were prepared in the presence of different amounts of phosphonoformic acid (PFA) via the hydrothermal method. The obtained powders were characterized through chemical analysis, XRD, IR, 31P MAS-NMR, TEM, and TG-TDA. The XRD showed that the PFA did not affect the apatite composition. Indeed, only a reduction of the crystallite size was noted. After grafting of PFA, the IR spectroscopy revealed the appearance of new bands belonging to HPO42- and carboxylate groups of the apatite and organic moiety, respectively. Moreover, the 31P MAS-NMR spectra exhibited a peak with a low intensity assigned to the terminal phosphonate group of the organic moiety in addition to that of the apatite. Based on these results, a reaction mechanism involving the surface hydroxyl groups (tbnd Casbnd OH) of the apatite and the carboxyl group of the acid was proposed.

Taraxinic acid, a hydrolysate of sesquiterpene lactone glycoside from the Taraxacum coreanum NAKAI, induces the differentiation of human acute promyelocytic leukemia HL-60 cells.

PubMed

Choi, Jung-Hye; Shin, Kyung-Min; Kim, Na-Young; Hong, Jung-Pyo; Lee, Yong Sup; Kim, Hyoung Ja; Park, Hee-Juhn; Lee, Kyung-Tae

2002-11-01

The present work was performed to elucidate the active moiety of a sesquiterpene lactone, taraxinic acid-1'-O-beta-D-glucopyranoside (1). from Taraxacum coreanum NAKAI on the cytotoxicity of various cancer cells. Based on enzymatic hydrolysis and MTT assay, the active moiety should be attributed to the aglycone taraxinic acid (1a). rather than the glycoside (1). Taraxinic acid exhibited potent antiproliferative activity against human leukemia-derived HL-60. In addition, this compound was found to be a potent inducer of HL-60 cell differentiation as assessed by a nitroblue tetrazolium reduction test, esterase activity assay, phagocytic activity assay, morphology change, and expression of CD 14 and CD 66 b surface antigens. These results suggest that taraxinic acid induces the differentiation of human leukemia cells to monocyte/macrophage lineage. Moreover, the expression level of c-myc was down-regulated during taraxinic acid-dependent HL-60 cell differentiation, whereas p21(CIP1) and p27(KIP1) were up-regulated. Taken together, our results suggest that taraxinic acid may have potential as a therapeutic agent in human leukemia.

Microbial Transformation of Esters of Chlorinated Carboxylic Acids

PubMed Central

Paris, D. F.; Wolfe, N. L.; Steen, W. C.

1984-01-01

Two groups of compounds were selected for microbial transformation studies. In the first group were carboxylic acid esters having a fixed aromatic moiety and an increasing length of the alkyl component. Ethyl esters of chlorine-substituted carboxylic acids were in the second group. Microorganisms from environmental waters and a pure culture of Pseudomonas putida U were used. The bacterial populations were monitored by plate counts, and disappearance of the parent compound was followed by gas-liquid chromatography as a function of time. The products of microbial hydrolysis were the respective carboxylic acids. Octanol-water partition coefficients (Kow) for the compounds were measured. These values spanned three orders of magnitude, whereas microbial transformation rate constants (kb) varied only 50-fold. The microbial rate constants of the carboxylic acid esters with a fixed aromatic moiety increased with an increasing length of alkyl substituents. The regression coefficient for the linear relationships between log kb and log Kow was high for group 1 compounds, indicating that these parameters correlated well. The regression coefficient for the linear relationships for group 2 compounds, however, was low, indicating that these parameters correlated poorly. PMID:16346459

Chromatographic Behaviour Predicts the Ability of Potential Nootropics to Permeate the Blood-Brain Barrier

PubMed Central

Farsa, Oldřich

2013-01-01

The log BB parameter is the logarithm of the ratio of a compound’s equilibrium concentrations in the brain tissue versus the blood plasma. This parameter is a useful descriptor in assessing the ability of a compound to permeate the blood-brain barrier. The aim of this study was to develop a Hansch-type linear regression QSAR model that correlates the parameter log BB and the retention time of drugs and other organic compounds on a reversed-phase HPLC containing an embedded amide moiety. The retention time was expressed by the capacity factor log k′. The second aim was to estimate the brain’s absorption of 2-(azacycloalkyl)acetamidophenoxyacetic acids, which are analogues of piracetam, nefiracetam, and meclofenoxate. Notably, these acids may be novel nootropics. Two simple regression models that relate log BB and log k′ were developed from an assay performed using a reversed-phase HPLC that contained an embedded amide moiety. Both the quadratic and linear models yielded statistical parameters comparable to previously published models of log BB dependence on various structural characteristics. The models predict that four members of the substituted phenoxyacetic acid series have a strong chance of permeating the barrier and being absorbed in the brain. The results of this study show that a reversed-phase HPLC system containing an embedded amide moiety is a functional in vitro surrogate of the blood-brain barrier. These results suggest that racetam-type nootropic drugs containing a carboxylic moiety could be more poorly absorbed than analogues devoid of the carboxyl group, especially if the compounds penetrate the barrier by a simple diffusion mechanism. PMID:23641330

Application of antibody-mediated extraction for the stereoselective determination of the active metabolite of loxoprofen in human and rat plasma.

PubMed

Takasaki, W; Tanaka, Y

1992-01-01

Antibody-mediated extraction followed by chiral high-performance liquid chromatography (HPLC) was applied to stereoselective determination in human and rat plasma of the active metabolite [(2S,1'R,2'S)-trans-alcohol] with three chiral centers of Loxoprofen, a 2-arylpropionic acid antiinflammatory agent after oral administration. Antiserum against the (1'R,2'S)-cyclopentanol moiety was obtained from a rabbit immunized with bovine serum albumin conjugate linked to the propionic acid moiety, in which another chiral center is located. Then, the immunoglobulin G purified by a protein A column was coupled to BrCN-activated Sepharose 4B. Plasma samples were applied to the immobilized antibody column. After washing the column to remove unrequired stereoisomers, a mixture of two diastereomers whose configurations were 1'R,2'S in the cyclopentanol moiety was extracted with 95% methanol. The solvent was evaporated and the residue was derivatized with (+)-(R)-1-(1-naphthyl)ethylamine as a chiral reagent to separate the diastereomers by HPLC. This combined analytical method showed the stereoselective metabolism of Loxoprofen in human, that is, 64% of the total amount of four trans-alcohol stereoisomers was in the 2S,1'R,2'S form, which is the active metabolite. This phenomenon was also observed in rats given Loxoprofen and its (2S)- and (2R)-isomers, and is explained by stereoselective ketone reduction of Loxoprofen to the (1'R,2'S)-trans-alcohol and inversion from 2R to 2S in the propionic acid moiety. Antibody-mediated extraction should be a selective and simple clean-up method for determining haptens with complicated structures, combined with an appropriate analytical method.

Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized using a Mizoroki–Heck cross-coupling reaction

PubMed Central

Huras, Bogumiła

2015-01-01

Summary Cinnamic acid derivatives bearing a nitroxyl moiety (2,2,6,6-tetramethyl-1-oxyl-4-piperidyl 3-E-aryl acrylates) were synthesized in 30–100% yield using a Mizoroki–Heck cross-coupling reaction between 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl and iodobenzene derivatives in the presence of palladium(II) acetate coordinated with a tri(o-tolyl)phosphine ligand immobilized in a polyurea matrix. PMID:26199672

Exploring bis-(indolyl)methane moiety as an alternative and innovative CAP group in the design of histone deacetylase (HDAC) inhibitors.

PubMed

Giannini, Giuseppe; Marzi, Mauro; Marzo, Maria Di; Battistuzzi, Gianfranco; Pezzi, Riccardo; Brunetti, Tiziana; Cabri, Walter; Vesci, Loredana; Pisano, Claudio

2009-05-15

In order to gather further knowledge about the structural requirements on histone deacetylase inhibitors (HDACi), starting from the schematic model of the common pharmacophore that characterizes this class of molecules (surface recognition CAP group-connection unit-linker region-Zinc Binding Group), we designed and synthesized a series of hydroxamic acids containing a bis-(indolyl)methane moiety. HDAC inhibition profile and antiproliferative activity were evaluated.

Synthesis and evaluations of an acid-cleavable, fluorescently labeled nucleotide as a reversible terminator for DNA sequencing.

PubMed

Tan, Lianjiang; Liu, Yazhi; Li, Xiaowei; Wu, Xin-Yan; Gong, Bing; Shen, Yu-Mei; Shao, Zhifeng

2016-02-11

An acid-cleavable linker based on a dimethylketal moiety was synthesized and used to connect a nucleotide with a fluorophore to produce a 3'-OH unblocked nucleotide analogue as an excellent reversible terminator for DNA sequencing by synthesis.

Anion sensing with a Lewis acidic BODIPY-antimony(v) derivative.

PubMed

Christianson, Anna M; Gabbaï, François P

2017-02-21

We describe the synthesis of a BODIPY dye substituted with a Lewis acidic antimony(v) moiety. This compound, which has been fully characterized, shows a high affinity for small anions including fluoride and cyanide, the complexation of which elicits a fluorescence turn-on response.

Eicosanoid signaling in insects: from discovery to plant protection

USDA-ARS?s Scientific Manuscript database

Prostaglandins (PGs) and related eicosanoids are signal moieties derived from arachidonic acid and two other C20 polyunsaturated fatty acids. They were discovered in the 1930s in the context of mammalian reproductive physiology; PGs were associated with the prostate gland, hence their name, and they...

Identification of Oxygenated Fatty Acid as a Side Chain of Lipo-Alkaloids in Aconitum carmichaelii by UHPLC-Q-TOF-MS and a Database.

PubMed

Liang, Ying; Wu, Jian-Lin; Leung, Elaine Lai-Han; Zhou, Hua; Liu, Zhongqiu; Yan, Guanyu; Liu, Ying; Liu, Liang; Li, Na

2016-03-31

Lipo-alkaloid is a kind of C19-norditerpenoid alkaloid usually found in Aconitum species. Structurally, they contain an aconitane skeleton and one or two fatty acid moieties of 3-25 carbon chains with 1-6 unsaturated degrees. Analysis of the lipo-alkaloids in roots of Aconitum carmichaelii resulted in the isolation of six known pure lipo-alkaloids (A1-A6) and a lipo-alkaloid mixture (A7). The mixture shared the same aconitane skeleton of 14-benzoylmesaconine, but their side chains were determined to be 9-hydroxy-octadecadienoic acid, 13-hydroxy-octadecadienoic acid and 10-hydroxy-octadecadienoic acid, respectively, by MS/MS analysis after alkaline hydrolysis. To our knowledge, this is the first time of the reporting of the oxygenated fatty acids as the side chains in naturally-occurring lipo-alkaloids. In order to identify more lipo-alkaloids, a compound database was established based on various combinations between the aconitane skeleton and the fatty acid chain, and then, the identification of lipo-alkaloids was conducted using the database, UHPLC-Q-TOF-MS and MS/MS. Finally, 148 lipo-alkaloids were identified from A. carmichaelii after intensive MS/MS analysis, including 93 potential new compounds and 38 compounds with oxygenated fatty acid moieties.

A Smart Molecule for Selective Sensing of Nitric Oxide: Conversion of NO to HSNO; Relevance of Biological HSNO Formation.

PubMed

Islam, Abu Saleh Musha; Bhowmick, Rahul; Pal, Kaberi; Katarkar, Atul; Chaudhuri, Keya; Ali, Mahammad

2017-04-17

A smart molecule, QT 490 , containing thiosemicarbazide moiety acts as a highly selective turn-on in vitro NO sensor through the unprecedented NO-induced transformation of thiosemicarbazide moiety to 1,3,4-oxadiazole heterocycle with the concomitant release of HSNO, thereby eliminating any interference from various endogenous biomolecules including dehydroascorbic acid, ascorbic acid, etc. The kinetic studies of the reactions between QT 490 and NO provide a mechanistic insight into formation of HSNO/RSNO from the reaction between H 2 S/RSH and NO in the biological system. This novel probe is non-cytotoxic, cell permeable, water-soluble, and appropriate for intracellular cytoplasmic NO sensing with the possibilities of in vivo applications.

Hydrogen bonding assemblies in host guest complexes with 18-crown-6

NASA Astrophysics Data System (ADS)

Fonari, M. S.; Simonov, Yu. A.; Kravtsov, V. Ch.; Lipkowski, J.; Ganin, E. V.; Yavolovskii, A. A.

2003-02-01

Recent X-ray crystal structural data for two novel 1:2 host-guest complexes of 18-crown-6 with neutral organic molecules, thiaamide hydrazide of 2-aminobenzoic acid and thiaamide hydrazide of 4-amino-1,2,5-thiadiazole-3-carbonic acid are reported. The supramolecular structures of these two and five relative complexes are discussed from the point of view of participation of donor groups in coordination with the crown ether, and donor and acceptor groups in the self-assembly of the guest molecules. Guest molecules have incorporated amine and hydrazine moieties as proton donors and carbonyl oxygen and sulfur (in thiadiazole and in thiaamine moieties) as proton acceptors. The guest-guest interactions appeared to be crucial in the final architecture.

Aging and behavior of functional TiO2 nanoparticles in aqueous environment.

PubMed

Lu, Huiting; Dong, Haifeng; Fan, Wenhong; Zuo, Jinxing; Li, Xiaomin

2017-03-05

Nanoparticles are usually functionalized with various surface capping moieties in practical applications. Understand the behavior and fate of them is critical to evaluate or even predict their risk to environment. However, little attention has been denoted on this issue until now. Using three commercial TiO 2 nanoparticles with different capping moieties, their aging procedures and corresponding change as well as their byproducts were systematically studied. Comprehensive microscopic and spectrometric measurements demonstrated a capping agent-dependent with the aging procedure. All the aging agents exhibited sharp change in morphologies compared to the fresh counterparts. The degraded degree and surface properties including surface charge and hydrophobicity of the functional TiO 2 nanoparticles were varied depended on the capping moieties. Furthermore, the behaviors of these byproducts in various background media had also been investigated. Contrastively, environment factors such as pH, electrolyte valence, and humic acid regardless of capping moieties govern the behavior of these byproducts, despite of the capping moieties slightly affect the point of zero charge. This study highlights the influence of the capping moieties and environmental factors to the transformation progress of functional nanomaterials in environment exposure, which contributes to design and assess the environmental risk of other analogous functional nanoparticles in practical application. Copyright © 2016 Elsevier B.V. All rights reserved.

Process for the combined removal of SO.sub.2 and NO.sub.x from flue gas

DOEpatents

Chang, Shih-Ger; Liu, David K.; Griffiths, Elizabeth A.; Littlejohn, David

1988-01-01

The present invention in one aspect relates to a process for the simultaneous removal of NO.sub.x and SO.sub.2 from a fluid stream comprising mixtures thereof and in another aspect relates to the separation, use and/or regeneration of various chemicals contaminated or spent in the process and which includes the steps of: (A) contacting the fluid stream at a temperature of between about 105.degree. and 180.degree. C. with a liquid aqueous slurry or solution comprising an effective amount of an iron chelate of an amino acid moiety having at least one --SH group; (B) separating the fluid stream from the particulates formed in step (A) comprising the chelate of the amino acid moiety and fly ash; (C) washing and separating the particulates of step (B) with an aqueous solution having a pH value of between about 5 to 8; (D) subsequently washing and separating the particulates of step (C) with a strongly acidic aqueous solution having a pH value of between about 1 to 3; (E) washing and separating the particulates of step (D) with an basic aqueous solution having a pH value of between about 9 to 12; (F) optionally adding additional amino acid moiety, iron (II) and alkali to the aqueous liquid from step (D) to produce an aqueous solution or slurry similar to that in step (A) having a pH value of between about 4 to 12; and (G) recycling the aqueous slurry of step (F) to the contacting zone of step (A). Steps (D) and (E) can be carried out in the reverse sequence, however the preferred order is (D) and then (E). In another preferred embodiment the present invention provides a process for the removal of NO.sub.x, SO.sub.2 and particulates from a fluid stream which includes the steps of (A) injecting into a reaction zone an aqueous solution itself comprising (i) an amino acid moiety selected from those described above; (ii) iron (II) ion; and (iii) an alkali, wherein the aqueous solution has a pH of between about 4 and 11; followed by solids separation and washing as is described in steps (B), (C), (D) and (E) above. The overall process is useful to reduce acid rain components from combustion gas sources.

Potential Role for a Carbohydrate Moiety in Anti-Candida Activity of Human Oral Epithelial Cells

PubMed Central

Steele, Chad; Leigh, Janet; Swoboda, Rolf; Ozenci, Hatice; Fidel, Paul L.

2001-01-01

Candida albicans is both a commensal and a pathogen at the oral mucosa. Although an intricate network of host defense mechanisms are expected for protection against oropharyngeal candidiasis, anti-Candida host defense mechanisms at the oral mucosa are poorly understood. Our laboratory recently showed that primary epithelial cells from human oral mucosa, as well as an oral epithelial cell line, inhibit the growth of blastoconidia and/or hyphal phases of several Candida species in vitro with a requirement for cell contact and with no demonstrable role for soluble factors. In the present study, we show that oral epithelial cell-mediated anti-Candida activity is resistant to gamma-irradiation and is not mediated by phagocytosis, nitric oxide, hydrogen peroxide, and superoxide oxidative inhibitory pathways or by nonoxidative components such as soluble defensin and calprotectin peptides. In contrast, epithelial cell-mediated anti-Candida activity was sensitive to heat, paraformaldehyde fixation, and detergents, but these treatments were accompanied by a significant loss in epithelial cell viability. Treatments that removed existing membrane protein or lipid moieties in the presence or absence of protein synthesis inhibitors had no effect on epithelial cell inhibitory activity. In contrast, the epithelial cell-mediated anti-Candida activity was abrogated after treatment of the epithelial cells with periodic acid, suggesting a role for carbohydrates. Adherence of C. albicans to oral epithelial cells was unaffected, indicating that the carbohydrate moiety is exclusively associated with the growth inhibition activity. Subsequent studies that evaluated specific membrane carbohydrate moieties, however, showed no role for sulfated polysaccharides, sialic acid residues, or glucose- and mannose-containing carbohydrates. These results suggest that oral epithelial cell-mediated anti-Candida activity occurs exclusively with viable epithelial cells through contact with C. albicans by an as-yet-undefined carbohydrate moiety. PMID:11598085

From N-triisopropylsilylpyrrole to an optically active C-4 substituted pyroglutamic acid: total synthesis of penmacric acid.

PubMed

Berini, Christophe; Pelloux-Léon, Nadia; Minassian, Frédéric; Denis, Jean-Noël

2009-11-07

The stereoselective synthesis of penmacric acid, an optically active C-4 substituted pyroglutamic acid, has been efficiently achieved through an unusual 11-step sequence starting from simple N-triisopropylsilylpyrrole. The key-steps are the initial addition of the pyrrole nucleus onto a chiral nitrone and the obtention of the pyroglutamic acid moiety by reductive hydrogenation of the pyrrole followed by oxidation of the corresponding pyrrolidine into pyrrolidinone.

Synthesis, analgesic activity, and binding properties of some epibatidine analogs with a tropine skeleton.

PubMed

Rádl, S; Hafner, W; Budesínsky, M; Hejnová, L; Krejcí, I

2000-06-01

A series of epibatidine analogs and their positional isomers bearing an 8-azabicyclo[3.2.1]octane moiety is described. Also some of their simplified analogs bearing a 3-piperidine moiety are reported. Their receptor binding profiles (5-HT1A, 5-HT1B, M1, M2, neuronal nicotinic receptor) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Some of the compounds, especially those containing an 8-azabicyclo[3.2.1]oct-2-ene moiety possess high afinity for the nicotinic cholinergic receptor. The most analgesically active compounds are also highly toxic. Optimized structures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of compounds 1-9 were compared with that of epibatidine.

[Chemical constituents from involatile moiety of Pogostemon cablin].

PubMed

Huang, Liejun; Mu, Shuzhen; Zhang, Jianxin; Deng, Bin; Song, Zhiqin; Hao, Xiaojiang

2009-02-01

To study the chemical constituents of involatile moiety of Pogostemon cablin. Compounds were isolated and purified by repeated column chromatography, and their structures were elucidated by spectroscopic analysis. Nine compounds have been isolated and identified: epifriedelinol (1), 5-hydroxymethol-2-furfural (2), succinic acid (3), beta-sitosterol (4), daucosterol (5), crenatoside (6), 3'''-O-methylcrenatoside (7), isocrenatoside (8), and apigenin-7-O-beta-D-(6"-p-coumaryl)-glucoside (9). Compounds 2, 3, 6-8 were isolated from Pogostemon genus for the first time.

Quantum Chemical and Physicochemical Studies of Oximes (Prophylactics against and Reactivators of Phosphorylated AChE).

DTIC Science & Technology

1984-10-25

crystal structure of nicotinic acid ,. and we used the ether bridge from the crystal structure of dimethyl ether. We are investigating various rotamers...observations were made: - The titration curve (after the subtraction of the blank curve) shows only one titrable group, i.e. the oxime moiety. - The...subtraction of the blank curve, shows two titrable groups, i.e. the two oxime moieties. The results are as follows: Temperature Conditions PKa pK2

Photoelectron resonance capture ionization-aerosol mass spectrometry of the ozonolysis products of oleic acid particles: Direct measure of higher molecular weight oxygenates

NASA Astrophysics Data System (ADS)

Zahardis, James; Lafranchi, Brian W.; Petrucci, Giuseppe A.

2005-04-01

The heterogeneous reaction of particle-phase 9-octadecenoic acid (oleic acid) and gas-phase ozone in a flow reactor was studied by photoelectron resonance capture ionization (PERCI) mass spectrometry. This soft ionization technique facilitated one of the first simultaneous, direct observations of all four of the major products predicted for this reaction: nonanal, nonanoic acid, 9-oxononanoic acid, and azelaic acid. In addition, a series of higher molecular weight oxygenated compounds were observed directly for the first time. The proposed structures are all cyclic oxygenates and contain the oxygen-oxygen moiety, including secondary ozonides and cyclic geminal diperoxides. Mechanisms for the formation of these products are proposed. The mechanisms are generally 1,3-dipolar cycloadditions that lead to five- and six-member oxygen-containing rings. The mechanisms are shown to involve short-lived Criegee intermediates reacting with aldehydes and other Criegee intermediates. Atmospheric implications of these higher molecular weight compounds are suggested and include enhancing the fatty acid medium's capacity to act as a source of radicals due to the prominence of the peroxide moiety. The low volatility coupled with the high polarity of these compounds may alter particle phase hygroscopicity that can enhance the cloud condensation nuclei properties of these particles.

Rerouting the Pathway for the Biosynthesis of the Side Ring System of Nosiheptide: The Roles of NosI, NosJ, and NosK

PubMed Central

2017-01-01

Nosiheptide (NOS) is a highly modified thiopeptide antibiotic that displays formidable in vitro activity against a variety of Gram-positive bacteria. In addition to a central hydroxypyridine ring, NOS contains several other modifications, including multiple thiazole rings, dehydro-amino acids, and a 3,4-dimethylindolic acid (DMIA) moiety. The DMIA moiety is required for NOS efficacy and is synthesized from l-tryptophan in a series of reactions that have not been fully elucidated. Herein, we describe the role of NosJ, the product of an unannotated gene in the biosynthetic operon for NOS, as an acyl carrier protein that delivers 3-methylindolic acid (MIA) to NosK. We also reassign the role of NosI as the enzyme responsible for catalyzing the ATP-dependent activation of MIA and MIA’s attachment to the phosphopantetheine moiety of NosJ. Lastly, NosK catalyzes the transfer of the MIA group from NosJ-MIA to a conserved serine residue (Ser102) on NosK. The X-ray crystal structure of NosK, solved to 2.3 Å resolution, reveals that the protein is an α/β-fold hydrolase. Ser102 interacts with Glu210 and His234 to form a catalytic triad located at the bottom of an open cleft that is large enough to accommodate the thiopeptide framework. PMID:28343381

Aspartic acid-based modified PLGA-PEG nanoparticles for bone targeting: in vitro and in vivo evaluation.

PubMed

Fu, Yin-Chih; Fu, Tzu-Fun; Wang, Hung-Jen; Lin, Che-Wei; Lee, Gang-Hui; Wu, Shun-Cheng; Wang, Chih-Kuang

2014-11-01

Nanoparticles (NP) that target bone tissue were developed using PLGA-PEG (poly(lactic-co-glycolic acid)-polyethylene glycol) diblock copolymers and bone-targeting moieties based on aspartic acid, (Asp)(n(1,3)). These NP are expected to enable the transport of hydrophobic drugs. The molecular structures were examined by (1)H NMR or identified using mass spectrometry and Fourier transform infrared (FT-IR) spectra. The NP were prepared using the water miscible solvent displacement method, and their size characteristics were evaluated using transmission electron microscopy (TEM) and dynamic light scattering. The bone targeting potential of the NP was evaluated in vitro using hydroxyapatite affinity assays and in vivo using fluorescent imaging in zebrafish and rats. It was confirmed that the average particle size of the NP was <200 nm and that the dendritic Asp3 moiety of the PLGA-PEG-Asp3 NP exhibited the best apatite mineral binding ability. Preliminary findings in vivo bone affinity assays in zebrafish and rats indicated that the PLGA-PEG-ASP3 NP may display increased bone-targeting efficiency compared with other PLGA-PEG-based NP that lack a dendritic Asp3 moiety. These NP may act as a delivery system for hydrophobic drugs, warranting further evaluation of the treatment of bone disease. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Lipoic acid metabolism and mitochondrial redox regulation.

PubMed

Solmonson, Ashley D; DeBerardinis, Ralph J

2017-11-30

Lipoic acid is an essential cofactor for mitochondrial metabolism and is synthesized de novo using intermediates from mitochondrial fatty acid synthesis type II, S-adenosylmethionine and iron-sulfur clusters. This cofactor is required for catalysis by multiple mitochondrial 2-ketoacid dehydrogenase complexes, including pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and branched-chain ketoacid dehydrogenase. Lipoic acid also plays a critical role in stabilizing and regulating these multi-enzyme complexes.  Many of these dehydrogenases are regulated by reactive oxygen species, mediated through the disulfide bond of the prosthetic lipoyl moiety.  Collectively, its functions explain why lipoic acid is required for cell growth, mitochondrial activity and coordination of fuel metabolism. Lipoic acid is an essential cofactor for mitochondrial metabolism and is synthesized de novo using intermediates from mitochondrial fatty acid synthesis type II, S-adenosylmethionine and iron-sulfur clusters. This cofactor is required for catalysis by multiple mitochondrial 2-ketoacid dehydrogenase complexes, including pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and branched-chain ketoacid dehydrogenase. Lipoic acid also plays a critical role in stabilizing and regulating these multi-enzyme complexes.  Many of these dehydrogenases are regulated by reactive oxygen species, mediated through the disulfide bond of the prosthetic lipoyl moiety.  Collectively, its functions explain why lipoic acid is required for cell growth, mitochondrial activity and coordination of fuel metabolism. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

Synthesis of pyridine-fused perylene imides with an amidine moiety for hydrogen bonding.

PubMed

Ito, Satoru; Hiroto, Satoru; Shinokubo, Hiroshi

2013-06-21

Pyridine-fused perylene tetracarboxylic acid bisimides (PBIs) were synthesized via Suzuki-Miyaura coupling and acid condensation. The fused PBIs with electron-donating substituents exhibited an intramolecular charge transfer interaction. One of the N-alkyl substituents was selectively removed with BBr3 to create an amidine guest binding site. A hydrogen bonding interaction with pentafluorobenzoic acid changed the absorption spectra and enhanced fluorescence.

Non-Invasive Nanodiagnostics of Cancer (NINOC)

DTIC Science & Technology

2010-04-01

tested. CONCLUSIONS Well-defined diblock copolymers of poly(ethylene glycol) and polymethacrylic acid (PEG-b-PMA) with aldehyde functionality were...treatment of cancer, tumor-specific targeting has been proposed using a variety of targeting moieties such as folic acid , transferrin, RGD-peptides...tert-butyl and PEG groups (Table 1). In order to obtain the final block copolymer 6, the hydrolysis of copolymer 5 was carried out in the acidic

Synthesis, electrochemical, structural, spectroscopic and biological activities of mixed ligand copper (II) complexes with 2-{[(Z)-(5-bromo-2-hydroxyphenyl)methylidene]amino}benzoic acid and nitrogenous bases

NASA Astrophysics Data System (ADS)

Choudhary, Mukesh; Patel, R. N.; Rawat, S. P.

2014-02-01

Three new copper (II) complexes viz. [Cu(L1)(bipy)]ṡ2H2O 1, [Cu(L1)(dmp)]ṡCH3CN 2, [Cu(L1)(phen)] 3 where L1H2 = 2-{[(Z)-(5-bromo-2-hydroxyphenyl)methylidene]amino}benzoic acid, bipy = 2,2‧-bipyridine; dmp = 2,9-dimethyl 1,10-phenanthroline, phen = 1,10-phenanthroline have been synthesized and characterized by physic-chemical and spectroscopic methods. The solid-state structures of 1 and 2 were determined by single crystal X-ray crystallography, which revealed distorted square pyramidal geometry. In solid-state structure, 1 is self-assembled via intermolecular π…π stacking and the distances between centroids of aromatic ring is 3.525 Å. L1H2 is a diprotic tridentate Schiff base ligand having ONO donor site. Infrared spectra, ligand field spectra and magnetic susceptibility measurements agree with the observed crystal structures. The EPR spectra of these complexes in frozen DMSO solutions showed a single at g ca. 2. The trend in g-value (g|| > g⊥ > 2.0023) suggests that the unpaired electron on copper (II) has d character. Copper (II) complexes 1-3 yielded an irreversible couple corresponding to the Cu (II)/Cu (I) redox process. Superoxide dismutase activity of all these complexes has been revealed to catalyze the dismutation of superoxide (O2-) and IC50 values were evaluated and discussed. Antimicrobial and antifungal activities of these complexes were also investigated.

Synthesis of molecularly imprinted organic-inorganic hybrid azobenzene materials by sol-gel for radiation induced selective recognition of 2,4-dichlorophenoxyacetic acid

NASA Astrophysics Data System (ADS)

Shuai Jiang, Guang; An Zhong, Shi; Chen, Lan; Blakey, Idriss; Whitaker, Andrew

2011-02-01

A novel photoresponsive functional monomer bearing a siloxane polymerisable group and azobenzene moieties was synthesized. This monomer was then used to prepare photoresponsive molecularly imprinted polymers (MIP), which have specific binding sites for 2,4-dichlorophenoxyacetic acid (2,4-D) through hydrogen bonding moieties. The binding affinity of the imprinted recognition sites was switchable by alternate irradiations with ultraviolet and visible light, suggesting that azobenzene groups located inside the binding sites could be used as chemical sensors and the trans-cis isomerization could regulate the affinity for the 2,4-D. In addition, the concentration of the 2,4-D was able to be quantified by monitoring the trans-to-cis photoisomerization rate constant.

Biosynthesis of the nargenicin A1 pyrrole moiety from Nocardia sp. CS682.

PubMed

Maharjan, Sushila; Aryal, Niraj; Bhattarai, Saurabh; Koju, Dinesh; Lamichhane, Janardan; Sohng, Jae Kyung

2012-01-01

A number of structurally diverse natural products harboring pyrrole moieties possess a wide range of biological activities. Studies on biosynthesis of pyrrole ring have shown that pyrrole moieties are derived from L-proline. Nargenicin A(1), a saturated alicyclic polyketide from Nocardia sp. CS682, is a pyrrole-2-carboxylate ester of nodusmicin. We cloned and identified a set of four genes from Nocardia sp. CS682 that show sequence similarity to the respective genes involved in the biosynthesis of the pyrrole moieties of pyoluteorin in Pseudomonas fluorescens, clorobiocin in Streptomyces roseochromogenes subsp. Oscitans, coumermycin A(1) in Streptomyces rishiriensis, one of the pyrrole rings of undecylprodigiosin in Streptomyces coelicolor, and leupyrrins in Sorangium cellulosum. These genes were designated as ngnN4, ngnN5, ngnN3, and ngnN2. In this study, we presented the evidences that the pyrrole moiety of nargenicin A(1) was also derived from L-proline by the coordinated action of three proteins, NgnN4 (proline adenyltransferase), NgnN5 (proline carrier protein), and NgnN3 (flavine-dependent acyl-coenzyme A dehydrogenases). Biosynthesis of pyrrole moiety in nargenicin A(1) is initiated by NgnN4 that catalyzes ATP-dependent activation of L-proline into L-prolyl-AMP, and the latter is transferred to NgnN5 to create prolyl-S-peptidyl carrier protein (PCP). Later, NgnN3 catalyzes the two-step oxidation of prolyl-S-PCP into pyrrole-2-carboxylate. Thus, this study presents another example of a pyrrole moiety biosynthetic pathway that uses a set of three genes to convert L-proline into pyrrole-2-carboxylic acid moiety.

Replacing the acetyl linkage in aspirin with choline and magnesium moieties reduces the occurrence of gastric mucosal injury.

PubMed

Danesh, B J; Nelson, L M; Russell, R I; Docherty, C

1987-02-01

The acetyl moiety in aspirin (acetyl salicylic acid: ASA) is considered to play a major part in the pathogenesis of ASA-induced mucosal injury. At equivalent salicylate doses and pH values, the induction of acute gastric mucosal haemorrhagic erosions in rats by ASA and choline magnesium trisalicylate (CMT), a new non-acetylated salicylate, with and without the potentiating damaging effect of taurodeoxycholic acid (TDCA) were compared. Test solutions were administered by per oral intubation to five groups of fasting Sprague-Dawley rats (n = 24). Gastric mucosa were examined after 4 hours and mucosal injury assessed by a lesion-scoring system. The incidence and severity (median lesion scores with quartiles) of the lesions were 83% and 13 (7:20) respectively for ASA (128 mg kg-1) compared with 17% and 0 (0:0) for CMT (128 mg kg-1) (P less than 0.001 and P less than 0.001). TDCA increased mucosal damage to 100% and 29 (20:34) for ASA compared with 30% and 0 (0:4) for CMT (P less than 0.001) and P less than 0.001). Serum salicylate levels (median values of 1.4 for ASA and 1.5 mmol litre-1 for CMT) were not significantly different. It is concluded that replacing the acetyl moiety in ASA with choline and magnesium moieties reduces the ASA-induced mucosal injury, without affecting blood salicylate concentrations.

Galloylglucoses of low molecular weight as mordant in electron microscopy. II. The moiety and functional groups possibly involved in the mordanting effect

PubMed Central

1976-01-01

Synthetic pentamonogalloylglucose applied to fixed tissues acts as a mordant, inducing high and diversified contrast similar to that obtained with natural gallotannins of low molecular weight (LMGG). By the separate use of each of the two moieties of the galloylglucose molecule, it was found that gallic acid is the mordanting agent. Glucose may contribute, however, to the effect by increasing the solubility and cross-linking potential of the compound, since the mordanting induced by gallic acid alone is weaker than that produced by its hexose esters. As suggested by results obtained with various phenolics and benzoic acid derivatives, the functional groups required for the mordanting effect of such agents are the carboxyl group, and at least one hydroxyl group concomitantly present on the benzene ring. In the case of galloylglucoses, it is assumed that the effect is due to hydrolysis products (gallic, digallic, or trigallic acids) or to the multiple hydroxyl groups of the intact molecule. Esters of gallic acid (propyl- and methylgallate), as well as pyrogallol, produce a "reversed staining" of all membranes, except for those of communicating (gap) junctions. PMID:783173

18O stable isotope labeling, quantitative model experiments, and molecular dynamics simulation studies on the trans-specific degradation of the bitter tasting iso-alpha-acids of beer.

PubMed

Intelmann, Daniel; Demmer, Oliver; Desmer, Nina; Hofmann, Thomas

2009-11-25

The typical bitterness of fresh beer is well-known to decrease in intensity and to change in quality with increasing age. This phenomenon was recently shown to be caused by the conversion of bitter tasting trans-iso-alpha-acids into lingering and harsh bitter tasting tri- and tetracyclic degradation products such as tricyclocohumol, tricyclocohumene, isotricyclocohumene, tetracyclocohumol, and epitetracyclocohumol. Interestingly, the formation of these compounds was shown to be trans-specific and the corresponding cis-iso-alpha-acids were found to be comparatively stable. Application of 18O stable isotope labeling as well as quantitative model studies combined with LC-MS/MS experiments, followed by computer-based molecular dynamics simulations revealed for the first time a conclusive mechanism explaining the stereospecific transformation of trans-iso-alpha-acids into the tri- and tetracyclic degradation products. This transformation was proposed to be induced by a proton-catalyzed carbon/carbon bond formation between the carbonyl atom C(1') of the isohexenoyl moiety and the alkene carbon C(2'') of the isoprenyl moiety of the trans-iso-alpha-acids.

Analysis of protein prenylation and S-acylation using gas chromatography-coupled mass spectrometry.

PubMed

Sorek, Nadav; Akerman, Amir; Yalovsky, Shaul

2013-01-01

Lipid modifications play a key role in protein targeting and function. The two Arabidopsis Gγ subunits, AGG1 and AGG2, have been shown to undergo prenylation (AGG1) and S-acylation (AGG2). Prenylation involves covalent nonreversible attachment of either farnesyl (15 carbons) or geranylgeranyl (20 carbons) isoprenoids to conserved cysteine residues at or near the C-terminus of proteins. S-acylation, frequently referred to as palmitoylation, involves the attachment of acyl fatty acids to thiol groups of cysteine residues through a reversible thioester bond. The procedures described below allow direct analysis of the prenyl and acyl moieties using gas chromatography-coupled mass spectrometry (GC-MS). These methods are based on (1) cleavage of prenyl groups with the Raney nickel catalyst and (2) analysis of protein S-acylation following cleavage of the acyl fatty acids from proteins by hydrogenation with platinum (IV) oxide. The hydrogenation under these conditions causes an acid transesterification of the acyl moieties, adding an ethyl group to the carboxyl head of the fatty acid. The addition of the ethyl group reduces the polarity of the fatty acids, allowing their efficient separation by gas chromatography.

Glutamic Acid Selective Chemical Cleavage of Peptide Bonds.

PubMed

Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika

2016-03-04

Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.

Polypeptide nanogels with hydrophobic moieties in the cross-linked ionic cores: Synthesis, characterization and implications for anticancer drug delivery

PubMed Central

Kim, Jong Oh; Oberoi, Hardeep S.; Desale, Swapnil; Kabanov, Alexander V.; Bronich, Tatiana K.

2014-01-01

Polymer nanogels have gained considerable attention as a potential platform for drug delivery applications. Here we describe the design and synthesis of novel polypeptide-based nanogels with hydrophobic moieties in the cross-linked ionic cores. Diblock copolymer, poly(ethylene glycol)-b-poly(L-glutamic acid), hydrophobically modified with L-phenylalanine methyl ester moieties was used for controlled template synthesis of nanogels with small size (ca. 70 nm in diameter) and narrow particle size distribution. Steady-state and time-resolved fluorescence studies using coumarin C153 indicated the existence of hydrophobic domains in the ionic cores of the nanogels. Stable doxorubicin-loaded nanogels were prepared at high drug capacity (30 w/w%). We show that nanogels are enzymatically-degradable leading to accelerated drug release under simulated lysosomal acidic pH. Furthermore, we demonstrate that the nanogel-based formulation of doxorubicin is well tolerated and exhibit an improved antitumor activity compared to a free doxorubicin in an ovarian tumor xenograft mouse model. Our results signify the point to a potential of these biodegradable nanogels as attractive carriers for delivery of chemotherapeutics. PMID:23998716

Discovery of a new class of histone deacetylase inhibitors with a novel zinc binding group.

PubMed

Li, Youxuan; Woster, Patrick M

2015-04-01

Small molecules featuring a hydroxamic acid or a benzamide zinc binding group (ZBG) are the most thoroughly studied histone deacetylase (HDAC) inhibitors. However, concerns about the pharmacokinetic liabilities of the hydroxamic acid moiety and potential metabolic toxicity of the aniline portion of benzamide HDAC inhibitors have stimulated research efforts aimed at discovering alternative ZBGs. Here we report the 2-(oxazol-2-yl)phenol moiety as a novel ZBG that can be used to produce compounds that are potent HDAC inhibitors. A series of analogues with this novel ZBG have been synthesized, and these analogues exhibit selective inhibition against HDAC1 as well as the class IIb HDACs (HDAC6 and HDAC10). Compound 10 possesses an IC 50 value of 7.5 μM in the MV-4-11 leukemia cell line, and induces a comparable amount of acetylated histone 3 lysine 9 (H3K9) and p21Waf1/CIP1 as 0.5 μM of SAHA. Modeling of compound 10 in the active site of HDAC2 demonstrates that the 2-(oxazol-2-yl)phenol moiety has a zinc-binding pattern similar to benzamide HDAC inhibitors.

Storage lipid biosynthesis in microspore-derived Brassica napus embryos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, D.C.; Underhill, E.W.; Weber, N.

1989-04-01

Erucic acid, a fatty acid which is confined to the neutral lipids in developing seed cotyledons or rape, was chosen as a marker to study triacylglycerol (TAG) biosynthesis in a Brassica napus L. cv Reston microspore-derived embryo culture system. Accumulation and changes in acyl composition of TAGs during embryogenesis strongly paralleled that observed during seed development. Homogenates of 29-day cultured embryos were examined for the ability to incorporate erucoyl moieties into storage lipids. In the presence of {sup 14}C erucoyl CoA and various acceptors, including glycerol-3-phosphate (G3P), {sup 14}C erucic acid was rapidly incorporated into the TAG fraction. However, inmore » contrast to studies with {sup 14}C oleoyl CoA, there was no measurable radioactivity in any Kennedy Pathway intermediates or within membrane lipid components. Analysis of the radiolabelled TAG species suggested that erucoyl moieties were incorporated into the sn-3 position by a highly active diacylglyercol acyltransferase.« less

Metabolism of adiphenine. I. Absorption, distribution and excretion in rats and mice.

PubMed

Michelot, J; Madelmont, J C; Jordan, D; Mornex, R; Meyniel, G

1981-02-01

1. The disposition of adiphenine labelled with 14C in two positions has been investigated in rats and mice after i.v. administration, and has been compared with that of the [14C]diethylethanolamine HCl and of the [14C]diphenylacetic acid. 2. Radioactivity in the blood declined in a biphasic manner. Biliary elimination depended upon the 14C-labelled compound administered: less than 5% dose for the diethylethanolamine moiety, 100% dose for the carboxylic moiety. Of the radioactivity appearing in rat bile, less than 1% is associated with unchanged adiphenine. 3. In preliminary metabolic studies, three major metabolites have been identified: diphenylacetic acid, diethylethanolamine and a diphenylacetic acid glucuronide. 4. Uptake by the brain of [14C]adiphenine shortly after dosing is 15 times greater than that of blood. Radioactivity is also found in the hypophysis, the adrenals and melanoid pigments, with a concn. up to 30 times greater than that found in the blood.

Ferricyanide-based analysis of aqueous lignin suspension revealed sequestration of water-soluble lignin moieties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joshua, C. J.; Simmons, B. A.; Singer, S. W.

This study describes the application of a ferricyanide-based assay as a simple and inexpensive assay for rapid analysis of aqueous lignin samples. The assay measures the formation of Prussian blue from the redox reaction between a mixture of potassium ferricyanide and ferric chloride, and phenolic hydroxyl groups of lignin or lignin-derived phenolic moieties. This study revealed that soluble lignin moieties exhibited stronger ferricyanide reactivity than insoluble aggregates. The soluble lignin moieties exhibited higher ferricyanide reactivity because of increased access of the phenolic hydroxyl groups to the ferricyanide reagents. Ferricyanide reactivity of soluble lignin moieties correlated inversely with the molecular weightmore » distributions of the molecules, probably due to the involvement of phenolic hydroxyl groups in bond formation. The insoluble lignin aggregates exhibited low ferricyanide reactivity due to sequestration of the phenolic hydroxyl groups within the solid matrix. The study also highlighted the sequestration of polydispersed water-soluble lignin moieties by insoluble aggregates. The sequestered moieties were released by treatment with 0.01 M NaOH at 37 °C for 180 min. The redox assay was effective on different types of lignin extracts such as Klason lignin from switchgrass, ionic-liquid derived lignin from Eucalyptus and alkali lignin extracts. The assay generated a distinct profile for each lignin sample that was highly reproducible. The assay was also used to monitor consumption of syringic acid by Sphingobium sp. SYK-6. The simplicity and reproducibility of this assay makes it an excellent and versatile tool for qualitative and semi-quantitative characterization and comparative profiling of aqueous lignin samples.« less

Ferricyanide-based analysis of aqueous lignin suspension revealed sequestration of water-soluble lignin moieties

DOE PAGES

Joshua, C. J.; Simmons, B. A.; Singer, S. W.

2016-06-02

This study describes the application of a ferricyanide-based assay as a simple and inexpensive assay for rapid analysis of aqueous lignin samples. The assay measures the formation of Prussian blue from the redox reaction between a mixture of potassium ferricyanide and ferric chloride, and phenolic hydroxyl groups of lignin or lignin-derived phenolic moieties. This study revealed that soluble lignin moieties exhibited stronger ferricyanide reactivity than insoluble aggregates. The soluble lignin moieties exhibited higher ferricyanide reactivity because of increased access of the phenolic hydroxyl groups to the ferricyanide reagents. Ferricyanide reactivity of soluble lignin moieties correlated inversely with the molecular weightmore » distributions of the molecules, probably due to the involvement of phenolic hydroxyl groups in bond formation. The insoluble lignin aggregates exhibited low ferricyanide reactivity due to sequestration of the phenolic hydroxyl groups within the solid matrix. The study also highlighted the sequestration of polydispersed water-soluble lignin moieties by insoluble aggregates. The sequestered moieties were released by treatment with 0.01 M NaOH at 37 °C for 180 min. The redox assay was effective on different types of lignin extracts such as Klason lignin from switchgrass, ionic-liquid derived lignin from Eucalyptus and alkali lignin extracts. The assay generated a distinct profile for each lignin sample that was highly reproducible. The assay was also used to monitor consumption of syringic acid by Sphingobium sp. SYK-6. The simplicity and reproducibility of this assay makes it an excellent and versatile tool for qualitative and semi-quantitative characterization and comparative profiling of aqueous lignin samples.« less

Synthesis and In Vitro Antimicrobial Evaluation of New 1,3,4-Oxadiazoles Bearing 5-Chloro-2-methoxyphenyl Moiety.

PubMed

Prasanna Kumar, Basavapatna N; Mohana, Kikkeri N; Mallesha, Lingappa; Harish, Kikkeri P

2013-01-01

A series of new 1,3,4-oxadiazole derivatives, 4(a-h), containing 5-chloro-2-methoxy benzohydrazide moiety were synthesized by the reaction of 5-chloro-2-methoxybenzoate with different aromatic carboxylic acids. These newly synthesized compounds were characterized by FT-IR, (1)H NMR, mass spectra, and also by elemental analysis. All the newly synthesized compounds were screened for their antibacterial and antifungal activities. Antimicrobial studies revealed that compounds 4c, 4f, and 4g showed significant activity against tested strains.

Protodeboronation of ortho- and para-phenol boronic acids and application to ortho and meta functionalization of phenols using boronic acids as blocking and directing groups.

PubMed

Lee, Chun-Young; Ahn, Su-Jin; Cheon, Cheol-Hong

2013-12-06

The first metal-free thermal protodeboronation of ortho- and para-phenol boronic acids in DMSO was developed. The protodeboronation was successfully applied to the synthesis of ortho- and meta-functionalized phenols using the boronic acid moiety as a blocking group and a directing group, respectively. Mechanistic studies suggested that this protodeboronation proceeds through the coordination of water to the boron atom followed by σ-bond metathesis.

Evolution of rosmarinic acid biosynthesis.

PubMed

Petersen, Maike; Abdullah, Yana; Benner, Johannes; Eberle, David; Gehlen, Katja; Hücherig, Stephanie; Janiak, Verena; Kim, Kyung Hee; Sander, Marion; Weitzel, Corinna; Wolters, Stefan

2009-01-01

Rosmarinic acid and chlorogenic acid are caffeic acid esters widely found in the plant kingdom and presumably accumulated as defense compounds. In a survey, more than 240 plant species have been screened for the presence of rosmarinic and chlorogenic acids. Several rosmarinic acid-containing species have been detected. The rosmarinic acid accumulation in species of the Marantaceae has not been known before. Rosmarinic acid is found in hornworts, in the fern family Blechnaceae and in species of several orders of mono- and dicotyledonous angiosperms. The biosyntheses of caffeoylshikimate, chlorogenic acid and rosmarinic acid use 4-coumaroyl-CoA from the general phenylpropanoid pathway as hydroxycinnamoyl donor. The hydroxycinnamoyl acceptor substrate comes from the shikimate pathway: shikimic acid, quinic acid and hydroxyphenyllactic acid derived from l-tyrosine. Similar steps are involved in the biosyntheses of rosmarinic, chlorogenic and caffeoylshikimic acids: the transfer of the 4-coumaroyl moiety to an acceptor molecule by a hydroxycinnamoyltransferase from the BAHD acyltransferase family and the meta-hydroxylation of the 4-coumaroyl moiety in the ester by a cytochrome P450 monooxygenase from the CYP98A family. The hydroxycinnamoyltransferases as well as the meta-hydroxylases show high sequence similarities and thus seem to be closely related. The hydroxycinnamoyltransferase and CYP98A14 from Coleus blumei (Lamiaceae) are nevertheless specific for substrates involved in RA biosynthesis showing an evolutionary diversification in phenolic ester metabolism. Our current view is that only a few enzymes had to be "invented" for rosmarinic acid biosynthesis probably on the basis of genes needed for the formation of chlorogenic and caffeoylshikimic acid while further biosynthetic steps might have been recruited from phenylpropanoid metabolism, tocopherol/plastoquinone biosynthesis and photorespiration.

Syntheses and mucosal adjuvant activity of simplified oleanolic acid saponins possessing cinnamoyl ester.

PubMed

Shirahata, Tatsuya; Nagai, Takayuki; Hirata, Nozomu; Yokoyama, Masaki; Katsumi, Tatsuya; Konishi, Naruki; Nishino, Takashi; Makino, Kazuishi; Yamada, Haruki; Kaji, Eisuke; Kiyohara, Hiroaki; Kobayashi, Yoshinori

2017-03-15

A series of new simplified oleanolic acid saponins with a glycosyl ester moiety at C28, were efficiently prepared. Furthermore, the effect of nasal administration of the synthetic oleanolic acid saponins on the nasal anti-influenza virus antibody titer against secondary nasal inoculation of the influenza split vaccine was examined. The result revealed cinnamoyl saponin as a suitable candidate vaccine adjuvant. Copyright © 2016. Published by Elsevier Ltd.

Direction to practical production of hydrogen by formic acid dehydrogenation with Cp*Ir complexes bearing imidazoline ligands

DOE PAGES

Onishi, Naoya; Ertem, Mehmed Z.; Xu, Shaoan; ...

2016-11-10

In a Cp*Ir complex with a bidentate pyridyl-imidazoline ligand achieved the evolution of 1.02 m 3 of H 2/CO 2 gases by formic acid dehydrogenation without any additives or adjustments in the solution system. Furthermore, the pyridyl-imidazoline moieties provided the optimum pH to be 1.7, resulting in high activity and stability even at very acidic conditions.

Direction to practical production of hydrogen by formic acid dehydrogenation with Cp*Ir complexes bearing imidazoline ligands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onishi, Naoya; Ertem, Mehmed Z.; Xu, Shaoan

In a Cp*Ir complex with a bidentate pyridyl-imidazoline ligand achieved the evolution of 1.02 m 3 of H 2/CO 2 gases by formic acid dehydrogenation without any additives or adjustments in the solution system. Furthermore, the pyridyl-imidazoline moieties provided the optimum pH to be 1.7, resulting in high activity and stability even at very acidic conditions.

Self assembling bioactive materials for cell adhesion in tissue repair

NASA Astrophysics Data System (ADS)

Hwang, Julia J.

This work involved the study of biodegradable and biocompatible materials that have the potential to modify tissue engineering scaffolds through self assembly, generating multiple layers that deliver bioactivity. Diblock biomaterials containing cholesteryl moieties and oligomers of lactic acid units were found to form single crystals when precipitated from hot ethanol and smectic liquid crystalline phases when cast as a film. Cell culture experiments on these films with 3T3 and 3T6 fibroblasts indicated that these ordered materials form surfaces with specific chemistries that favored cell adhesion, spreading, and proliferation suggesting the potential of mediating human tissue repair. The author believes the cholesteryl moieties found on the surface play a key role in determining cell behavior. Cholesteryl-(L-lactic acid) diblock molecules were then functionalized with moieties including vitamin Bx, cholesterol, and the anti-inflammatory drug indomethacin. An unstable activated ester between indomethacin and the diblock molecule resulted in the release of indomethacin into the culture medium which inhibited the proliferation of 3T3 fibroblasts. Finally, a series of molecules were designed to incorporate dendrons based on amino acids at the termini of the diblock structures. It was determined that lysine, a basic amino acid, covalently coupled to cholesteryl-(L-lactic acid) can promote cell adhesion and spreading while negatively charged and zwitterionic 2nd generation dendrons based on aspartic acid do not. Incorporation of the well known arginine-glycine-aspartic acid (RGD) sequence, which is found in many adhesive proteins, to the dendrons imparted integrin-mediated cell adhesion as evidenced by the formation of stress fibers. We also explored the capacity of integrin receptors to bind to ligands that are not the linear form of RGD, but have R, G, and D spatially positioned to mimic the linear RGD environments. For this purpose, the arms of the 2 nd generation lysine dendrons were functionalized with R, G, and D to yield an 'R,G,D library' of molecules. These materials were found to promote adhesion of 3T3 fibroblasts through integrin receptors. A dendron is multifunctional and allows a large degree of functionality in chemical design.

FY08 Chemical Synthesis for the Self-Decontaminating Coatings Project

DTIC Science & Technology

2013-08-01

These synthesized materials consist of Boltorn hyperbranched polymers that are functionalized with hydantoin, alkyl, and perfluorinated groups. 15...envisioned that completely prevents sorption of chemical agents, enables autonomous decontamination, reduces the volume of cleaning solution...modified with perfluorinated octanoic acid (PFOA), lauric acid, and a hydantoin moiety. HO OH CH3 HO O 3 Figure 2. Synthetic targets 1–3

Antihypertensive effect of caffeic acid and its analogs through dual renin-angiotensin-aldosterone system inhibition.

PubMed

Bhullar, Khushwant S; Lassalle-Claux, Grégoire; Touaibia, Mohamed; Rupasinghe, H P Vasantha

2014-05-05

Hypertension is a crucial risk factor for cardiovascular diseases and contributes to one third of global mortality. In addition to conventional antihypertensive drugs such as captopril, naturally occurring phytochemicals and their analogs are used for reducing the risk and occurrence of hypertension. Herein, we demonstrate the possible use of caffeic acid and its derivatives in the treatment of hypertension through multi-target modulation of renin-angiotensin-aldosterone system (RAAS). Caffeic acid along with its nineteen novel derivatives, chlorogenic acid, quercetin and captopril were all investigated for the inhibition of renin and angiotensin converting enzyme (ACE) activities and production of aldosterone. Compound 22 with CH2CH(Ph)2 moiety exhibited the strongest renin inhibition (IC50=229µM) among all compounds tested (P≤0.05). Caffeic acid was the weakest renin inhibitor (IC50=5704µM) among all the compounds assayed. Similar to renin inhibition, compound 22 (IC50=9.1µM) also exhibited about 47 times stronger ACE inhibition compared to the parent compound. Analysis of aldosterone revealed that compound 8 with n-Pr moiety was the strongest modulator of aldosterone production among all the derivatives (P≤0.05). Toxicity analysis using human fibroblasts (WI-38 cells) confirmed the non-toxic manifestations of caffeic acid and its derivatives in comparison to clinically used drug captopril. Copyright © 2014 Elsevier B.V. All rights reserved.

Spin labelled nitrosoureas and triazenes and their non-labelled clinically used analogues--a comparative study on their physicochemical properties and antimelanomic effects.

PubMed

Zheleva, A M; Gadjeva, V G

2001-01-16

Physicochemical properties, such as half life time (tau0.5), alkylating and carbamoylating activity and in vivo antimelanomic effects against B16 melanoma of spin labeled (containing nitroxyl free radical moiety) amino acid nitrosoureas, synthesized in our laboratory, have been studied and compared to those of the antitumor drug N'-cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU). We have shown that the introduction of amino acid moieties and the replacement of cyclohexylamine with nitroxyl moiety leads to a faster decomposition, higher alkylating, lower carbamoylating activity, better antimelanomic activity and lower general toxicity, when compared to those of CCNU. It was also established that spin labeled triazenes, previously synthesized by us, were more stable in phosphate saline than their nonlabeled analogue, 5-(3,3-dimethyltriazene-1-yl)-imidazole-4-carboxamide (dacarbazine, DTIC). A higher cytotoxicity to B16 melanoma cells than to YAC-1 and lymphocytes was demonstrated for all spin labeled triazenes, in comparison with DTIC. An assumption has been made to explain the lower general toxicity of the spin labeled nitrosoureas compared to that of CCNU. Based on the results presented, we accept that a new trend for synthesis of more selective and less toxic nitrosourea and triazene derivatives as potential antimelanomic drugs might be developed.

Pimelic acid, the first precursor of the Bacillus subtilis biotin synthesis pathway, exists as the free acid and is assembled by fatty acid synthesis.

PubMed

Manandhar, Miglena; Cronan, John E

2017-05-01

Biotin synthetic pathways are readily separated into two stages, synthesis of the seven carbon α, ω-dicarboxylic acid pimelate moiety and assembly of the fused heterocyclic rings. The biotin pathway genes responsible for pimelate moiety synthesis vary widely among bacteria whereas the ring synthesis genes are highly conserved. Bacillus subtilis seems to have redundant genes, bioI and bioW, for generation of the pimelate intermediate. Largely consistent with previous genetic studies it was found that deletion of bioW caused a biotin auxotrophic phenotype whereas deletion of bioI did not. BioW is a pimeloyl-CoA synthetase that converts pimelic acid to pimeloyl-CoA. The essentiality of BioW for biotin synthesis indicates that the free form of pimelic acid is an intermediate in biotin synthesis although this is not the case in E. coli. Since the origin of pimelic acid in Bacillus subtilis is unknown, 13 C-NMR studies were carried out to decipher the pathway for its generation. The data provided evidence for the role of free pimelate in biotin synthesis and the involvement of fatty acid synthesis in pimelate production. Cerulenin, an inhibitor of the key fatty acid elongation enzyme, FabF, markedly decreased biotin production by B. subtilis resting cells whereas a strain having a cerulenin-resistant FabF mutant produced more biotin. In addition, supplementation with pimelic acid fully restored biotin production in cerulenin-treated cells. These results indicate that pimelic acid originating from fatty acid synthesis pathway is a bona fide precursor of biotin in B. subtilis. © 2017 John Wiley & Sons Ltd.

Dual chain synthetic heparin-binding growth factor analogs

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY

2012-04-24

The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

Dual chain synthetic heparin-binding growth factor analogs

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY

2009-10-06

The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

Synthesis and In Vitro Antimicrobial Evaluation of New 1,3,4-Oxadiazoles Bearing 5-Chloro-2-methoxyphenyl Moiety

PubMed Central

Prasanna Kumar, Basavapatna N.; Mohana, Kikkeri N.; Mallesha, Lingappa; Harish, Kikkeri P.

2013-01-01

A series of new 1,3,4-oxadiazole derivatives, 4(a–h), containing 5-chloro-2-methoxy benzohydrazide moiety were synthesized by the reaction of 5-chloro-2-methoxybenzoate with different aromatic carboxylic acids. These newly synthesized compounds were characterized by FT-IR, 1H NMR, mass spectra, and also by elemental analysis. All the newly synthesized compounds were screened for their antibacterial and antifungal activities. Antimicrobial studies revealed that compounds 4c, 4f, and 4g showed significant activity against tested strains. PMID:25374693

Functionalization of Cyclodextrins with N-Hydroxyphthalimide Moiety: A New Class of Supramolecular Pro-Oxidant Organocatalysts.

PubMed

Melone, Lucio; Petroselli, Manuel; Pastori, Nadia; Punta, Carlo

2015-08-31

N-hydroxyphthalimide (NHPI) is an organocatalyst for free-radical processes able to promote the aerobic oxidation of a wide range of organic substrates. In particular, NHPI can catalyze the hydroperoxidation of polyunsaturated fatty acids (PUFA). This property could be of interest for biological applications. This work reports the synthesis of two β-cyclodextrin derivatives (CD5 and CD6) having a different degree of methylation and bearing a NHPI moiety. These compounds, having different solubility in water, have been successfully tested for the hydroperoxidation of methyl linoleate, chosen as the PUFA model molecule.

Discovery of a low-systemic-exposure DGAT-1 inhibitor with a picolinoylpyrrolidine-2-carboxylic acid moiety.

PubMed

Yan, Jianwei; Wang, Gaihong; Dang, Xiangyu; Guo, Binbin; Chen, Wuhong; Wang, Ting; Zeng, Limin; Wang, Heyao; Hu, Youhong

2017-09-01

A series of diacylglycerol O-acyltransferase 1 (DGAT-1) inhibitors with a picolinoylpyrrolidine-2-carboxylic acid moiety were designed and synthesized. Of these compounds, compound 22 exhibited excellent DGAT-1-inhibitory activity (hDGAT-1 enzyme assay, 50% inhibitory concentration [IC 50 ]=3.5±0.9nM) and effectively reduced the intracellular triglyceride contents in 3T3-L1, HepG2 and Caco-2 cells. A preliminary study of the plasma and tissue distributions of compound 22 in mice revealed low plasma exposure and high concentrations in different segments of the intestine and liver, which may facilitate targeting DGAT-1. Furthermore, in an acute lipid challenge test, compound 22 showed a dose-dependent inhibitory effect on high-serum triglycerides in C57/KSJ mice induced by olive oil (1, 3, and 10mg/kg, i.g.). Copyright © 2017 Elsevier Ltd. All rights reserved.

Design, Synthesis, and Biological Functionality of a Dendrimer-based Modular Drug Delivery Platform

PubMed Central

Mullen, Douglas G.; McNerny, Daniel Q.; Desai, Ankur; Cheng, Xue-min; DiMaggio, Stassi C.; Kotlyar, Alina; Zhong, Yueyang; Qin, Suyang; Kelly, Christopher V.; Thomas, Thommey P.; Majoros, Istvan; Orr, Bradford G.; Baker, James R.; Banaszak Holl, Mark M.

2011-01-01

A modular dendrimer-based drug delivery platform was designed to improve upon existing limitations in single dendrimer systems. Using this modular strategy, a biologically active platform containing receptor mediated targeting and fluorescence imaging modules was synthesized by coupling a folic acid (FA) conjugated dendrimer with a fluorescein isothiocyanate (FITC) conjugated dendrimer. The two different dendrimer modules were coupled via the 1,3-dipolar cycloaddition reaction (‘click’ chemistry) between an alkyne moiety on the surface of the first dendrimer and an azide moiety on the second dendrimer. Two simplified model systems were also synthesized to develop appropriate ‘click’ reaction conditions and aid in spectroscopic assignments. Conjugates were characterized by 1H NMR spectroscopy and NOESY. The FA-FITC modular platform was evaluated in vitro with a human epithelial cancer cell line (KB) and found to specifically target the over-expressed folic acid receptor. PMID:21425790

Heterofibrins: inhibitors of lipid droplet formation from a deep-water southern Australian marine sponge, Spongia (Heterofibria) sp.

PubMed

Salim, Angela A; Rae, James; Fontaine, Frank; Conte, Melissa M; Khalil, Zeinab; Martin, Sally; Parton, Robert G; Capon, Robert J

2010-07-21

A bioassay-guided search for inhibitors of lipid droplet formation in a deep-water southern Australian marine sponge, Spongia (Heterofibria) sp., yielded six new compounds, fatty acids heterofibrins A1 (1) and B1 (4), along with related monolactyl and dilactyl esters, heterofibrins A2 (2), B2 (5), A3 (3) and B3 (6). Heterofibrin structures were assigned on the basis of detailed spectroscopic analysis, with comparison to chiral synthetic model compounds. All heterofibrins possess a diyne-ene moiety, while the monolactyl and dilactyl moiety featured in selected heterofibrins is unprecedented in the natural products literature. SAR by co-metabolite studies on the heterofibrins confirmed them to be non-cytotoxic, with the carboxylic acids 1 and 4 inhibiting lipid droplet formation in A431 fibroblast cell lines. Such inhibitors have potential application in the management of obesity, diabetes and atherosclerosis

Egg Yolk Factor of Staphylococcus aureus II. Characterization of the Lipase Activity

PubMed Central

Shah, D. B.; Wilson, J. B.

1965-01-01

Shah, D. B. (University of Wisconsin, Madison), and J. B. Wilson. Egg yolk factor of Staphylococcus aureus. II. Characterization of the lipase activity. J. Bacteriol. 89:949–953. 1965.—The staphylococcal egg yolk factor was characterized as a lipase. The enzyme had an optimal pH of 7.8, but the optimal pH of stability was 7. Substrate specificity data showed that the relative rate of hydrolysis was lowest with triacetin as substrate, was maximal with tributyrin, and decreased as the chain length of the acyl moieties increased. The enzyme showed an absolute requirement for a fatty acid acceptor like calcium, when the acyl moiety of triglyceride was water-insoluble. Magnesium, strontium, and barium functioned equally well as fatty acid acceptors. The enzyme was able to hydrolyze coconut oil, peanut oil, olive oil, and egg yolk oil. PMID:14276120

Cage-like bifunctional chelators, copper-64 radiopharmaceuticals and PET imaging using the same

DOEpatents

Conti, Peter S.; Cai, Hancheng; Li, Zibo; Liu, Shuanglong

2016-08-02

Disclosed is a class of versatile Sarcophagine based bifunctional chelators (BFCs) containing a hexa-aza cage for labeling with metals having either imaging, therapeutic or contrast applications radiolabeling and one or more linkers (A) and (B). The compounds have the general formula ##STR00001## where A is a functional group selected from group consisting of an amine, a carboxylic acid, an ester, a carbonyl, a thiol, an azide and an alkene, and B is a functional group selected from the group consisting of hydrogen, an amine, a carboxylic acid, and ester, a carbonyl, a thiol, an azide and an alkene. Also disclosed are conjugate of the BFC and a targeting moiety, which may be a peptide or antibody. Also disclosed are metal complexes of the BFC/targeting moiety conjugates that are useful as radiopharmaceuticals, imaging agents or contrast agents.

Synthesis, Characterization, Topographical Modification, and Surface Properties of Copoly(Imide Siloxane)s

NASA Technical Reports Server (NTRS)

Wohl, Christopher J.; Atkins, Brad M.; Belcher, Marcus A.; Connell, John W.

2012-01-01

Novel copoly(imide siloxane)s were synthesized from commercially available aminopropyl terminated siloxane oligomers, aromatic dianhydrides, and diamines. This synthetic approach produced copolymers with well-defined siloxane blocks linked with imide units in a random fashion. The copoly(amide acid)s were characterized by solution viscosity and subsequently used to cast thin films followed by thermal imidization in an inert atmosphere. Thin films were characterized using contact angle goniometry, attenuated total reflection Fourier transform infrared spectroscopy, confocal and optical microscopy, and tensile testing. Adhesion of micronsized particles was determined quantitatively using a sonication device. The polydimethylsiloxane (PDMS) moieties lowered the copolymer surface energy due to migration of siloxane moieties to the film s surface, resulting in a notable reduction in particle adhesion. A further reduction in particle adhesion was achieved by introducing topographical features on a scale of several to tens of microns by a laser ablation technique.

A highly selective fluorescent probe for the detection of hypochlorous acid in tap water and living cells.

PubMed

Wang, Xiao; Zhou, Yanmei; Xu, Chenggong; Song, Haohan; Li, Li; Zhang, Junli; Guo, Meixia

2018-06-03

A turn-on fluorescent probe (DAME) for sensing hypochlorous acid (HClO) with excellent selectivity was presented. The fluorescent probe was composed of coumarin derivative as the fluorophore and dimethylcarbamothioic chloride group with a sulfide moiety as modulator. Additionally, the sulfide moiety would be oxidized by HClO, and then free dye of coumarin derivate was released and exhibited significant fluorescence. In addition, the probe could respond to HClO in solutions within 60 s and the limit of detection was down to 34.75 nM. Moreover, the probe was used for the detection of HClO in tap water through the home-made test paper. And confocal images confirmed that probe DAME could be used for recognizing HClO in living cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Catabolism of exogenous deoxyinosine in cultured epithelial amniotic cells.

PubMed

Carta, M C; Mattana, A; Camici, M; Allegrini, S; Tozzi, M G; Sgarrella, F

2001-10-03

Uptake and catabolism of purine nucleosides have been commonly considered as means to salvage the purine ring for nucleic acid synthesis, usually neglecting the destiny of the pentose moiety. With the aim to ascertain if deoxyribose derived from exogenous DNA can be utilised as a carbon and energy source, we studied the catabolism of exogenous deoxyinosine in a cell line derived from human amnion epithelium (WISH). Intact WISH cells catabolise deoxyinosine by conversion into hypoxanthine. The nucleoside enters the cell through a nitrobenzylthioinosine-insensitive equilibrative transport. Deoxyinosine undergoes a phosphorolytic cleavage inside the cell. The purine base diffuses back to the external medium, while the phosphorylated pentose moiety can be further catabolised to glycolysis and citric acid cycle intermediates. Our results indicate that the catabolism of the deoxynucleoside can be considered mainly as a means to meet the carbon and energy requirements of growing cells.

Multiple Animal Studies for Medical Chemical Defense Program in Soldier/ Patient Decontamination and Drug Development on Task Order 84-6: Pyruvate Dehydrogenase System for Determining the Effectiveness of Arsenic Antidotes

DTIC Science & Technology

1988-03-11

adenine dinucleotide FAD = flavin-adenine dinucleotide iipS2 = lipoic acid lip(SH)2 = dihydrolipoic acid CoA = coenzyme A. SHepatic PDH complex activity...tissues has yet to be fully characterized, but it probably involves arsenic binding to the lipoic acid and dithiol moieties of the complex (Fluharty...covalently bound lipoic acid substrate of dihydrolipoyl transacetylase is greater per mole of L and CVAA than for sodium arsenite. This is possible

Discovery of trans-4-[1-[[2,5-Dichloro-4-(1-methyl-3-indolylcarboxamido)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid: an orally active, selective very late antigen-4 antagonist.

PubMed

Muro, Fumihito; Iimura, Shin; Sugimoto, Yuuichi; Yoneda, Yoshiyuki; Chiba, Jun; Watanabe, Toshiyuki; Setoguchi, Masaki; Iigou, Yutaka; Matsumoto, Keiko; Satoh, Atsushi; Takayama, Gensuke; Taira, Tomoe; Yokoyama, Mika; Takashi, Tohru; Nakayama, Atsushi; Machinaga, Nobuo

2009-12-24

We have focused on optimization of the inadequate pharmacokinetic profile of trans-4-substituted cyclohexanecarboxylic acid 5, which is commonly observed in many small molecule very late antigen-4 (VLA-4) antagonists. We modified the lipophilic moiety in 5 and found that reducing the polar surface area of this moiety results in improvement of the PK profile. Consequently, our efforts have led to the discovery of trans-4-[1-[[2,5-dichloro-4-(1-methyl-3-indolylcarboxamido)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid (14e) with potent activity (IC(50) = 5.4 nM) and significantly improved bioavailability in rats, dogs, and monkeys (100%, 91%, 68%), which demonstrated excellent oral efficacy in murine and guinea pig models of asthma. Based on its overall profile, compound 14e was progressed into clinical trails. In a single ascending-dose phase I clinical study, compound 14e exhibited favorable oral exposure as expected and had no serious adverse events.

Two distinct domains contribute to the substrate acyl chain length selectivity of plant acyl-ACP thioesterase.

PubMed

Jing, Fuyuan; Zhao, Le; Yandeau-Nelson, Marna D; Nikolau, Basil J

2018-02-28

The substrate specificity of acyl-ACP thioesterase (TE) plays an essential role in controlling the fatty acid profile produced by type II fatty acid synthases. Here we identify two groups of residues that synergistically determine different substrate specificities of two acyl-ACP TEs from Cuphea viscosissima (CvFatB1 and CvFatB2). One group (V194, V217, N223, R226, R227, and I268 in CvFatB2) is critical in determining the structure and depth of a hydrophobic cavity in the N-terminal hotdog domain that binds the substrate's acyl moiety. The other group (255-RKLSKI-260 and 285-RKLPKL-289 in CvFatB2) defines positively charged surface patches that may facilitate binding of the ACP moiety. Mutagenesis of residues within these two groups results in distinct synthetic acyl-ACP TEs that efficiently hydrolyze substrates with even shorter chains (C4- to C8-ACPs). These insights into structural determinants of acyl-ACP TE substrate specificity are useful in modifying this enzyme for tailored fatty acid production in engineered organisms.

Discovery of a novel acyl-CoA: cholesterol acyltransferase inhibitor: the synthesis, biological evaluation, and reduced adrenal toxicity of (4-phenylcoumarin)acetanilide derivatives with a carboxylic acid moiety.

PubMed

Ogino, Masaki; Nakada, Yoshihisa; Negoro, Nobuyuki; Itokawa, Shigekazu; Nishimura, Satoshi; Sanada, Tsukasa; Satomi, Tomoko; Kita, Shunbun; Kubo, Kazuki; Marui, Shogo

2011-01-01

As a part of our research for novel potent and orally available acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors that can be used as anti-atherosclerotic agents, we recently reported the discovery of the (4-phenylcoumarine)acetanilide derivative 1. However, compound 1 showed adrenal toxicity in animal models. In order to search for safer ACAT inhibitors that do not have adrenal toxicity, we examined the inhibitory activity of ACAT in human macrophage and adrenal cells. The introduction of a carboxylic acid moiety on the pendant phenyl ring and the adjustment of the lipophilicity led to the discovery of (2E)-3-[7-chloro-3-[2-[[4-fluoro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl]-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]acrylic acid (21e), which showed potent ACAT inhibitory activity in macrophages and a selectivity of around 30-fold over adrenal cells. In addition, compound 21e showed high adrenal safety in guinea pigs.

Novel trans-Ferulic Acid Derivatives Containing a Chalcone Moiety as Potential Activator for Plant Resistance Induction.

PubMed

Gan, Xiuhai; Hu, Deyu; Wang, Yanjiao; Yu, Lu; Song, Baoan

2017-06-07

A series of novel trans-ferulic acid derivatives containing a chalcone moiety were designed and synthesized to induce plant resistance. Antiviral activities of the compounds were evaluated. Bioassay results demonstrated that compounds F3, F6, F17, and F27 showed remarkable curative, protective, and inactivating activities against tobacco mosaic virus (TMV). With a 50% effective concentration (EC 50 ) value of 98.78 μg mL -1 , compound F27 exhibited the best protective activity compared with trans-ferulic acid (328.6 μg mL -1 ), dufulin (385.6 μg mL -1 ), and ningnanmycin (241.3 μg mL -1 ). This protective ability was associated with potentiation of defense-related enzyme activity and activation of photosynthesis of tobacco at an early stage. This notion was confirmed by up-regulated expression of stress responses and photosynthesis regulating proteins. This work revealed that F27 can induce resistance and enhance plant tolerance to TMV infection. Hence, F27 can be considered as a novel activator for inducing plant resistance.

Derivatizations of Sgc8-c aptamer to prepare metallic radiopharmaceuticals as imaging diagnostic agents: Syntheses, isolations, and physicochemical characterizations.

PubMed

Sicco, Estefanía; Báez, Jessica; Margenat, Jimena; García, Fernanda; Ibarra, Manuel; Cabral, Pablo; Moreno, María; Cerecetto, Hugo; Calzada, Victoria

2018-03-01

Aptamers, oligonucleotides with the capability to bind to a target through non-covalent bonds with high affinity and specificity, have a great number of advantages as scaffold to prepare molecular imaging agents. In this sense, we have performed post-SELEX modifications of a truncated aptamer, Sgc8-c, which bind to protein tyrosine kinase 7 to obtain a specific molecular targeting probe for in vivo diagnosis and in vivo therapy. Herein, we describe the synthetic efforts to prepare conjugates between Sgc8-c and different metallic ions chelator moieties in short times, high purities, and adequate yields. The selected chelator moieties, derived from 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 2-benzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid, and 6-hydrazinonicotinic acid, were covalently attached at the 5'-aptamer position yielding the expected products which were stable in aqueous solution up to 75°C and in typical aptamer storage conditions at least for 30 days. © 2017 John Wiley & Sons A/S.

Clarithromycin and Tetracycline Binding to Soil Humic Acid in the Absence and Presence of Calcium.

PubMed

Christl, Iso; Ruiz, Mercedes; Schmidt, J R; Pedersen, Joel A

2016-09-20

Numerous ionizable organic micropollutants contain positively charged moieties at pH values typical of environmental systems. Describing organic cation and zwitterion interaction with dissolved natural organic matter requires explicit consideration of the pH-dependent speciation of both sorbate and sorbent. We studied the pH-, ionic strength-, and concentration-dependent binding of relatively large, organic cations and zwitterions (viz., the antibiotics clarithromycin and tetracycline) to dissolved humic acid in the absence and presence of Ca(2+) and evaluated the ability of the NICA-Donnan model to describe the data. Clarithromycin interaction with dissolved humic acid was well described by the model including the competitive effect of Ca(2+) on clarithromycin binding over a wide range of solution conditions by considering only the binding of the cationic species to low proton-affinity sites in humic acid. Tetracycline possesses multiple ionizable moieties and forms complexes with Ca(2+). An excellent fit to experimental data was achieved by considering tetracycline cation interaction with both low and high proton-affinity sites of humic acid and zwitterion interaction with high proton-affinity sites. In contrast to clarithromycin, tetracycline binding to humic acid increased in the presence of Ca(2+), especially under alkaline conditions. Model calculations indicate that this increase is due to electrostatic interaction of positively charged tetracycline-Ca complexes with humic acid rather than due to the formation of ternary complexes, except at very low TC concentrations.

Development of Novel Environmentally Sustainable Binders for Energetic Formulations

DTIC Science & Technology

2015-06-01

Senenayake, C. H., Addition of Grignard reagents to aryl acid chlorides: an efficient synthesis of aryl ketones, Org. Lett. 2005, 7, 5593- 5595. (b) Gowda...M. S.; Pande, S. S.; Ramakrishna, R. A.; Prabhu, K. R., Acylation of Grignard reagents mediated by N-methylpyrrolidinone: a remarkable selectivity...acid moiety to introduce the necessary linker. Although the standard isocyanates- based reagents induce significant toxicity, the isocyanate function

Acidic Ribosomal Proteins from the Extreme ’Halobacterium cutirubrum’,

DTIC Science & Technology

the extreme halophilic bacterium, Halobacterium cutirubrum. The identification of the protein moieties involved in these and other interactions in...the halophile ribosome requires a rapid and reproducible screening method for the separation, enumeration and identification of these acidic...polypeptides in the complex ribosomal protein mixtures. In this paper the authors present the results of analyses of the halophile ribosomal proteins using a

Signal Transduction by BvgS Sensor Kinase

PubMed Central

Dupré, Elian; Lesne, Elodie; Guérin, Jérémy; Lensink, Marc F.; Verger, Alexis; de Ruyck, Jérôme; Brysbaert, Guillaume; Vezin, Hervé; Locht, Camille; Antoine, Rudy; Jacob-Dubuisson, Françoise

2015-01-01

The two-component sensory transduction system BvgAS controls the virulence regulon of the whooping-cough agent Bordetella pertussis. The periplasmic moiety of the homodimeric sensor kinase BvgS is composed of four bilobed Venus flytrap (VFT) perception domains followed by α helices that extend into the cytoplasmic membrane. In the virulent phase, the default state of B. pertussis, the cytoplasmic enzymatic moiety of BvgS acts as kinase by autophosphorylating and transferring the phosphoryl group to the response regulator BvgA. Under laboratory conditions, BvgS shifts to phosphatase activity in response to modulators, notably nicotinate ions. Here we characterized the effects of nicotinate and related modulators on the BvgS periplasmic moiety by using site-directed mutagenesis and in silico and biophysical approaches. Modulators bind with low affinity to BvgS in the VFT2 cavity. Electron paramagnetic resonance shows that their binding globally affects the conformation and dynamics of the periplasmic moiety. Specific amino acid substitutions designed to slacken interactions within and between the VFT lobes prevent BvgS from responding to nicotinate, showing that BvgS shifts from kinase to phosphatase activity in response to this modulator via a tense transition state that involves a large periplasmic structural block. We propose that this transition enables the transmembrane helices to adopt a distinct conformation that sets the cytoplasmic enzymatic moiety in the phosphatase mode. The bona fide, in vivo VFT ligands that remain to be identified are likely to trigger similar effects on the transmembrane and cytoplasmic moieties. This mechanism may be relevant to the other VFT-containing sensor kinases homologous to BvgS. PMID:26203186

Benzimidazoles and benzoxazoles via the nucleophilic addition of anilines to nitroalkanes.

PubMed

Aksenov, Alexander V; Smirnov, Alexander N; Aksenov, Nicolai A; Bijieva, Asiyat S; Aksenova, Inna V; Rubin, Michael

2015-04-14

PPA-induced umpolung triggers efficient nucleophilic addition of unactivated anilines to nitroalkanes to produce N-hydroxyimidamides. The latter undergo sequential acid-promoted cyclocondensation with ortho-OH or ortho-NHR moieties to afford benzoxazoles and benzimidazoles, respectively.

Interaction of Mimetic Analogs of Insect Kinin Neuropeptides with Arthropod Receptors

DTIC Science & Technology

2010-01-01

stagnalis.20 The amino acid sequence of the B. microplus receptor showed most similarity to the CG10626 Drosophila melanogaster gene product and to the...25 The A. aegypti cDNA encodes a 584 amino acid residue protein of predicted molecular mass of 65.2 kDa. The mosquito kinin receptor cDNA was...charged acid moiety.36,37 Within the core pentapeptide, the aromatic residues Phe1 and Trp4 are the most important for activity whereas a wide range

Accumulation of medium-chain, saturated fatty acyl moieties in seed oils of transgenic Camelina sativa.

PubMed

Hu, Zhaohui; Wu, Qian; Dalal, Jyoti; Vasani, Naresh; Lopez, Harry O; Sederoff, Heike W; Qu, Rongda

2017-01-01

With its high seed oil content, the mustard family plant Camelina sativa has gained attention as a potential biofuel source. As a bioenergy crop, camelina has many advantages. It grows on marginal land with low demand for water and fertilizer, has a relatively short life cycle, and is stress tolerant. As most other crop seed oils, camelina seed triacylglycerols (TAGs) consist of mostly long, unsaturated fatty acyl moieties, which is not desirable for biofuel processing. In our efforts to produce shorter, saturated chain fatty acyl moieties in camelina seed oil for conversion to jet fuel, a 12:0-acyl-carrier thioesterase gene, UcFATB1, from California bay (Umbellularia californica Nutt.) was expressed in camelina seeds. Up to 40% of short chain laurate (C12:0) and myristate (C14:0) were present in TAGs of the seed oil of the transgenics. The total oil content and germination rate of the transgenic seeds were not affected. Analysis of positions of these two fatty acyl moieties in TAGs indicated that they were present at the sn-1 and sn-3 positions, but not sn-2, on the TAGs. Suppression of the camelina KASII genes by RNAi constructs led to higher accumulation of palmitate (C16:0), from 7.5% up to 28.5%, and further reduction of longer, unsaturated fatty acids in seed TAGs. Co-transformation of camelina with both constructs resulted in enhanced accumulation of all three medium-chain, saturated fatty acids in camelina seed oils. Our results show that a California bay gene can be successfully used to modify the oil composition in camelina seed and present a new biological alternative for jet fuel production.

Accumulation of medium-chain, saturated fatty acyl moieties in seed oils of transgenic Camelina sativa

PubMed Central

Dalal, Jyoti; Vasani, Naresh; Lopez, Harry O.; Sederoff, Heike W.

2017-01-01

With its high seed oil content, the mustard family plant Camelina sativa has gained attention as a potential biofuel source. As a bioenergy crop, camelina has many advantages. It grows on marginal land with low demand for water and fertilizer, has a relatively short life cycle, and is stress tolerant. As most other crop seed oils, camelina seed triacylglycerols (TAGs) consist of mostly long, unsaturated fatty acyl moieties, which is not desirable for biofuel processing. In our efforts to produce shorter, saturated chain fatty acyl moieties in camelina seed oil for conversion to jet fuel, a 12:0-acyl-carrier thioesterase gene, UcFATB1, from California bay (Umbellularia californica Nutt.) was expressed in camelina seeds. Up to 40% of short chain laurate (C12:0) and myristate (C14:0) were present in TAGs of the seed oil of the transgenics. The total oil content and germination rate of the transgenic seeds were not affected. Analysis of positions of these two fatty acyl moieties in TAGs indicated that they were present at the sn-1 and sn-3 positions, but not sn-2, on the TAGs. Suppression of the camelina KASII genes by RNAi constructs led to higher accumulation of palmitate (C16:0), from 7.5% up to 28.5%, and further reduction of longer, unsaturated fatty acids in seed TAGs. Co-transformation of camelina with both constructs resulted in enhanced accumulation of all three medium-chain, saturated fatty acids in camelina seed oils. Our results show that a California bay gene can be successfully used to modify the oil composition in camelina seed and present a new biological alternative for jet fuel production. PMID:28212406

A process for the preparation of cysteine from cystine

DOEpatents

Chang, Shih-Ger; Liu, David K.; Griffiths, Elizabeth A.; Littlejohn, David

1989-01-01

The present invention in one aspect relates to a process for the simultaneous removal of NO.sub.x and SO.sub.2 from a fluid stream comprising mixtures thereof and in another aspect relates to the separation, use and/or regeneration of various chemicals contaminated or spent in the process and which includes the steps of: (A) contacting the fluid stream at a temperature of between about 105.degree. and 180.degree. C. with a liquid aqueous slurry or solution comprising an effective amount of an iron chelate of an amino acid moiety having at least one --SH group; (B) separating the fluid stream from the particulates formed in step (A) comprising the chelate of the amino acid moiety and fly ash; (C) washing and separating the particulates of step (B) with an aqeous solution having a pH value of between about 5 to 8; (D) subsequently washing and separating the particulates of step (C) with a strongly acidic aqueous solution having a pH value of between about 1 to 3; (E) washing and separating the particulates of step (D) with an basic aqueous solution having a pH value of between about 9 to 12; (F) optionally adding additional amino acid moiety, iron (II) and alkali to the aqueous liquid from step (D) to produce an aqueous solution or slurry similar to that in step (A) having a pH value of between about 4 to 12; and (G) recycling the aqueous slurry of step (F) to the contacting zone of step (A). Steps (D) and (E) can be carried out in the reverse sequence, however the preferred order is (D) and then (E). In a preferred embodiment the present invention provides an improved process for the preparation (regeneration) of cysteine from cystine, which includes reacting an aqueous solution of cystine at a pH of between about 9 to 13 with a reducing agent selected from hydrogen sulfide or alkali metal sulfides, sulfur dioxide, an alkali metal sulfite or mixtures thereof for a time and at a temperature effective to cleave and reduce the cystine to cysteine with subsequent recovery of the cysteine. In another preferred embodiment the present invention provides a process for the removal of NO.sub.x, SO.sub.2 and particulates from a fluid stream which includes the steps of (A) injecting into a reaction zone an aqueous solution itself comprising (i) an amino acid moiety selected from those described above; (ii) iron (II) ion; and (iii) an alkali, wherein the aqueous solution has a pH of between about 4 and 11; followed by solids separation and washing as is described in steps (B), (C), (D) and (E) above. The overall process is useful to reduce acid rain components from combustion gas sources.

Leukotriene B4 omega-hydroxylase in human polymorphonuclear leukocytes. Suicidal inactivation by acetylenic fatty acids.

PubMed

Shak, S; Reich, N O; Goldstein, I M; Ortiz de Montellano, P R

1985-10-25

Human polymorphonuclear leukocytes (PMN) not only generate and respond to leukotriene B4 (LTB4), but also catabolize this mediator of inflammation rapidly and specifically by omega-oxidation (probably due to the action of a cytochrome P-450 enzyme). To develop pharmacologically useful inhibitors of the LTB4 omega-hydroxylase in human PMN, we devised a general scheme for synthesizing terminal acetylenic fatty acids based on the "acetylenic zipper" reaction. We found that the LTB4 omega-hydroxylase in intact PMN and in PMN sonicates is inactivated in a concentration-dependent fashion by terminal acetylenic analogues of lauric, palmitic, and stearic acids (i.e. 11-dodecynoic, 15-hexadecynoic, and 17-octadecynoic acids). Consistent with a suicidal process, inactivation of the LTB4 omega-hydroxylase requires molecular oxygen and NADPH, is time-dependent, and follows pseudo-first-order kinetics. Inactivation of the omega-hydroxylase by acetylenic fatty acids also is dependent on the terminal acetylenic moiety and the carbon chain length. Saturated fatty acids lacking a terminal acetylenic moiety do not inactivate the omega-hydroxylase. In addition, the two long-chain (C16, C18) acetylenic fatty acids inactivate the omega-hydroxylase at much lower concentrations (less than 5.0 microM) than those required for inactivation by the short-chain (C12) terminal acetylenic fatty acid (100 microM). Potent suicidal inhibitors of the LTB4 omega-hydroxylase in human PMN will help elucidate the roles played by LTB4 and its omega-oxidation products in regulating PMN function and in mediating inflammation.

Selective fluorescent detection of aspartic acid and glutamic acid employing dansyl hydrazine dextran conjugate.

PubMed

Nasomphan, Weerachai; Tangboriboonrat, Pramuan; Tanapongpipat, Sutipa; Smanmoo, Srung

2014-01-01

Highly water soluble polymer (DD) was prepared and evaluated for its fluorescence response towards various amino acids. The polymer consists of dansyl hydrazine unit conjugated into dextran template. The conjugation enhances higher water solubility of dansyl hydrazine moiety. Of screened amino acids, DD exhibited selective fluorescence quenching in the presence of aspartic acid (Asp) and glutamic acid (Glu). A plot of fluorescence intensity change of DD against the concentration of corresponding amino acids gave a good linear relationship in the range of 1 × 10(-4) M to 25 × 10(-3) M. This establishes DD as a potential polymeric sensor for selective sensing of Asp and Glu.

LEWIS ACID CATALYZED FORMATION OF TETRAHYDROPYRANS IN IONIC LIQUID

EPA Science Inventory

Tetrahydropyrans are integral moieties in innumerable natural products and have inspired the development of a variety of different methodologies. A Prins-type cyclization involving the coupling of a homoallylic alcohol and an aldehyde in the presence of catalytic scandium triflat...

Catalytic Aminohalogenation of Alkenes and Alkynes

PubMed Central

Chemler, Sherry R.; Bovino, Michael T.

2013-01-01

Catalytic aminohalogenation methods enable the regio- and stereoselective vicinal difunctionalization of alkynes, allenes and alkenes with amine and halogen moieties. A range of protocols and reaction mechanisms including organometallic, Lewis base, Lewis acid and Brønsted acid catalysis have been disclosed, enabling the regio- and stereoselective synthesis of halogen-functionalized acyclic amines and nitrogen heterocycles. Recent advances including aminofluorination and catalytic enantioselective aminohalogenation reactions are summarized in this review. PMID:23828735

Catalytic Aminohalogenation of Alkenes and Alkynes.

PubMed

Chemler, Sherry R; Bovino, Michael T

2013-06-07

Catalytic aminohalogenation methods enable the regio- and stereoselective vicinal difunctionalization of alkynes, allenes and alkenes with amine and halogen moieties. A range of protocols and reaction mechanisms including organometallic, Lewis base, Lewis acid and Brønsted acid catalysis have been disclosed, enabling the regio- and stereoselective synthesis of halogen-functionalized acyclic amines and nitrogen heterocycles. Recent advances including aminofluorination and catalytic enantioselective aminohalogenation reactions are summarized in this review.

Polysaccharide-gold nanocluster supramolecular conjugates as a versatile platform for the targeted delivery of anticancer drugs.

PubMed

Li, Nan; Chen, Yong; Zhang, Ying-Ming; Yang, Yang; Su, Yue; Chen, Jia-Tong; Liu, Yu

2014-02-25

Through the high affinity of the β-cyclodextrin (β-CD) cavity for adamantane moieties, novel polysaccharide-gold nanocluster supramolecular conjugates (HACD-AuNPs) were successfully constructed from gold nanoparticles (AuNPs) bearing adamantane moieties and cyclodextrin-grafted hyaluronic acid (HACD). Due to their porous structure, the supramolecular conjugates could serve as a versatile and biocompatible platform for the loading and delivery of various anticancer drugs, such as doxorubicin hydrochloride (DOX), paclitaxel (PTX), camptothecin (CPT), irinotecan hydrochloride (CPT-11), and topotecan hydrochloride (TPT), by taking advantage of the controlled association/dissociation of drug molecules from the cavities formed by the HACD skeletons and AuNPs cores as well as by harnessing the efficient targeting of cancer cells by hyaluronic acid. Significantly, the release of anticancer drugs from the drug@HACD-AuNPs system was pH-responsive, with more efficient release occurring under a mildly acidic environment, such as that in a cancer cell. Taking the anticancer drug DOX as an example, cell viability experiments revealed that the DOX@HACD-AuNPs system exhibited similar tumor cell inhibition abilities but lower toxicity than free DOX due to the hyaluronic acid reporter-mediated endocytosis. Therefore, the HACD-AuNPs supramolecular conjugates may possess great potential for the targeted delivery of anticancer drugs.

Polysaccharide-Gold Nanocluster Supramolecular Conjugates as a Versatile Platform for the Targeted Delivery of Anticancer Drugs

NASA Astrophysics Data System (ADS)

Li, Nan; Chen, Yong; Zhang, Ying-Ming; Yang, Yang; Su, Yue; Chen, Jia-Tong; Liu, Yu

2014-02-01

Through the high affinity of the β-cyclodextrin (β-CD) cavity for adamantane moieties, novel polysaccharide-gold nanocluster supramolecular conjugates (HACD-AuNPs) were successfully constructed from gold nanoparticles (AuNPs) bearing adamantane moieties and cyclodextrin-grafted hyaluronic acid (HACD). Due to their porous structure, the supramolecular conjugates could serve as a versatile and biocompatible platform for the loading and delivery of various anticancer drugs, such as doxorubicin hydrochloride (DOX), paclitaxel (PTX), camptothecin (CPT), irinotecan hydrochloride (CPT-11), and topotecan hydrochloride (TPT), by taking advantage of the controlled association/dissociation of drug molecules from the cavities formed by the HACD skeletons and AuNPs cores as well as by harnessing the efficient targeting of cancer cells by hyaluronic acid. Significantly, the release of anticancer drugs from the drug@HACD-AuNPs system was pH-responsive, with more efficient release occurring under a mildly acidic environment, such as that in a cancer cell. Taking the anticancer drug DOX as an example, cell viability experiments revealed that the DOX@HACD-AuNPs system exhibited similar tumor cell inhibition abilities but lower toxicity than free DOX due to the hyaluronic acid reporter-mediated endocytosis. Therefore, the HACD-AuNPs supramolecular conjugates may possess great potential for the targeted delivery of anticancer drugs.

Reminiscence of phospholipase B in Penicillium notatum

PubMed Central

SAITO, Kunihiko

2014-01-01

Since the phospholipase B (PLB) was reported as a deacylase of both lecithin and lysolecithin yielding fatty acids and glycerophosphocholine (GPC), there was a question as to whether it is a single enzyme or a mixture of a phospholipase A2 (PLA2) and a lysophospholipase (LPL). We purified the PLB in Penicillium notatum and showed that it catalyzed deacylation of sn-1 and sn-2 fatty acids of 1,2-diacylphospholipids and also sn-1 or sn-2 fatty acids of 1- or 2-monoacylphospholipids (lysophospholipids). Further, it also has a monoacyllipase activity. The purified PLB is a glycoprotein with m.w. of 91,300. The sugar moiety is M9 only and the protein moiety consists of 603 amino acids. PLB, different from PLA2, shows other enzymatic activities, such as transacylase, lipase and acylesterase. PLB activity is influenced by various substances, e.g. detergents, deoxycholate, diethylether, Fe3+, and endogenous protease. Therefore, PLB might have broader roles than PLA2 in vivo. The database shows an extensive sequence similarity between P. notatum PLB and fungal PLB, cPLA2 and patatin, suggesting a homologous relationship. The catalytic triad of cPLA2, Ser, Asp and Arg, is also present in P. notatum PLB. Other related PLBs, PLB/Lipases are discussed. PMID:25391318

Structure-Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist (2S,3R)-3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid.

PubMed

Krogsgaard-Larsen, Niels; Storgaard, Morten; Møller, Charlotte; Demmer, Charles S; Hansen, Jeanette; Han, Liwei; Monrad, Rune N; Nielsen, Birgitte; Tapken, Daniel; Pickering, Darryl S; Kastrup, Jette S; Frydenvang, Karla; Bunch, Lennart

2015-08-13

Herein we describe the first structure-activity relationship study of the broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring the pharmacological effect of substituents in the 4, 4', or 5' positions and the bioisosteric substitution of the distal carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4' position 2a which induced a preference in binding affinity for homomeric GluK3 over GluK1 (Ki = 0.87 and 4.8 μM, respectively). Two X-ray structures of ligand binding domains were obtained: 2e in GluA2-LBD and 2f in GluK1-LBD, both at 1.9 Å resolution. Compound 2e induces a D1-D2 domain opening in GluA2-LBD of 17.3-18.8° and 2f a domain opening in GluK1-LBD of 17.0-17.5° relative to the structures with glutamate. The pyrrolidine-2-carboxylate moiety of 2e and 2f shows a similar binding mode as kainate. The 3-carboxyphenyl ring of 2e and 2f forms contacts comparable to those of the distal carboxylate in kainate.

Gene Therapy for Infectious Diseases

PubMed Central

Bunnell, Bruce A.; Morgan, Richard A.

1998-01-01

Gene therapy is being investigated as an alternative treatment for a wide range of infectious diseases that are not amenable to standard clinical management. Approaches to gene therapy for infectious diseases can be divided into three broad categories: (i) gene therapies based on nucleic acid moieties, including antisense DNA or RNA, RNA decoys, and catalytic RNA moieties (ribozymes); (ii) protein approaches such as transdominant negative proteins and single-chain antibodies; and (iii) immunotherapeutic approaches involving genetic vaccines or pathogen-specific lymphocytes. It is further possible that combinations of the aforementioned approaches will be used simultaneously to inhibit multiple stages of the life cycle of the infectious agent. PMID:9457428

Purification and characterization of acid trehalase from the yeast suc2 mutant.

PubMed

Mittenbühler, K; Holzer, H

1988-06-15

Acid trehalase was purified from the yeast suc2 deletion mutant. After hydrophobic interaction chromatography, the enzyme could be purified to a single band or peak by a further step of either polyacrylamide gel electrophoresis, gel filtration, or isoelectric focusing. An apparent molecular mass of 218,000 Da was calculated from gel filtration. Polyacrylamide gel electrophoresis of the purified enzyme in the presence of sodium dodecyl sulfate suggested a molecular mass of 216,000 Da. Endoglycosidase H digestion of the purified enzyme resulted after sodium dodecyl sulfate gel electrophoresis in one distinct band at 41,000 Da, representing the mannose-free protein moiety of acid trehalase. The carbohydrate content of the enzyme was 86%. Amino acid analysis indicated 354 residues/molecule of enzyme including 9 cysteine moieties and only 1 methionine. The isoelectric point of the enzyme was estimated by gel electrofocusing to be approximately 4.7. The catalytic activity showed a maximum at pH 4.5. The activity of the enzyme was not inhibited by 10 mM each of HgCl2, EDTA, iodoacetic acid, phenanthrolinium chloride or phenylmethylsulfonyl fluoride. There was no activation by divalent metal ions. The acid trehalase exhibited an apparent Km for trehalose of 4.7 +/- 0.1 mM and a Vmax of 99 mumol of trehalose min-1 X mg-1 at 37 degrees C and pH 4.5. The acid trehalase is located in the vacuoles. The rabbit antiserum raised against acid trehalase exhibited strong cross-reaction with purified invertase. These cross-reactions were removed by affinity chromatography using invertase coupled to CNBr-activated Sepharose 4B. Precipitation of acid trehalase activity was observed with the purified antiserum.

Modulation of FadR Binding Capacity for Acyl-CoA Fatty Acids Through Structure-Guided Mutagenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bacik, John-Paul; Yeager, Chris M.; Twary, Scott N.

FadR is a versatile global regulator in Escherichia coli that controls fatty acid metabolism and thereby modulates the ability of this bacterium to grow using fatty acids or acetate as the sole carbon source. FadR regulates fatty acid metabolism in response to intra-cellular concentrations of acyl-CoA lipids. The ability of FadR to bind acyl-CoA fatty acids is hence of significant interest for the engineering of biosynthetic pathways for the production of lipid-based biofuels and commodity chemicals. Based on the available crystal structure of E. coli bound to myristoyl- CoA, we predicted amino acid positions within the effector binding pocket thatmore » would alter the ability of FadR to bind acyl-CoA fatty acids without affecting DNA binding. We utilized fluorescence polarization to characterize the in-vitro binding properties of wild type and mutant FadR. We found that a Leu102Ala mutant enhanced binding of the effector, likely by increasing the size of the binding pocket for the acyl moiety of the molecule. Conversely, the elimination of the guanidine side chain (Arg213Ala and Arg213Met mutants) of the CoA moiety binding site severely diminished the ability of FadR to bind the acyl-CoA effector. These results demonstrate the ability to fine tune FadR binding capacity. The validation of an efficient method to fully characterize all the binding events involved in the specific activity (effector and DNA operator binding) of FadR has allowed us to increase our understanding of the role of specific amino acids in the binding and recognition of acyl-CoA fatty acids and will greatly facilitate efforts aimed at engineering tunable FadR regulators for synthetic biology.« less

Modulation of FadR Binding Capacity for Acyl-CoA Fatty Acids Through Structure-Guided Mutagenesis

DOE PAGES

Bacik, John-Paul; Yeager, Chris M.; Twary, Scott N.; ...

2015-09-18

FadR is a versatile global regulator in Escherichia coli that controls fatty acid metabolism and thereby modulates the ability of this bacterium to grow using fatty acids or acetate as the sole carbon source. FadR regulates fatty acid metabolism in response to intra-cellular concentrations of acyl-CoA lipids. The ability of FadR to bind acyl-CoA fatty acids is hence of significant interest for the engineering of biosynthetic pathways for the production of lipid-based biofuels and commodity chemicals. Based on the available crystal structure of E. coli bound to myristoyl- CoA, we predicted amino acid positions within the effector binding pocket thatmore » would alter the ability of FadR to bind acyl-CoA fatty acids without affecting DNA binding. We utilized fluorescence polarization to characterize the in-vitro binding properties of wild type and mutant FadR. We found that a Leu102Ala mutant enhanced binding of the effector, likely by increasing the size of the binding pocket for the acyl moiety of the molecule. Conversely, the elimination of the guanidine side chain (Arg213Ala and Arg213Met mutants) of the CoA moiety binding site severely diminished the ability of FadR to bind the acyl-CoA effector. These results demonstrate the ability to fine tune FadR binding capacity. The validation of an efficient method to fully characterize all the binding events involved in the specific activity (effector and DNA operator binding) of FadR has allowed us to increase our understanding of the role of specific amino acids in the binding and recognition of acyl-CoA fatty acids and will greatly facilitate efforts aimed at engineering tunable FadR regulators for synthetic biology.« less

Self-assembling nucleic acid delivery vehicles via linear, water-soluble, cyclodextrin-containing polymers.

PubMed

Davis, M E; Pun, S H; Bellocq, N C; Reineke, T M; Popielarski, S R; Mishra, S; Heidel, J D

2004-01-01

Non-viral (synthetic) nucleic acid delivery systems have the potential to provide for the practical application of nucleic acid-based therapeutics. We have designed and prepared a tunable, non-viral nucleic acid delivery system that self-assembles with nucleic acids and centers around a new class of polymeric materials; namely, linear, water-soluble cyclodextrin-containing polymers. The relationships between polymer structure and gene delivery are illustrated, and the roles of the cyclodextrin moieties for minimizing toxicity and forming inclusion complexes in the self-assembly processes are highlighted. This vehicle is the first example of a polymer-based gene delivery system formed entirely by self-assembly.

Phenylalanine-427 of anthrax protective antigen functions in both pore formation and protein translocation.

PubMed

Sun, Jianjun; Lang, Alexander E; Aktories, Klaus; Collier, R John

2008-03-18

The protective antigen (PA) moiety of anthrax toxin forms a heptameric pore in endosomal membranes of mammalian cells and translocates the enzymatic moieties of the toxin to the cytosol of these cells. Phenylalanine-427 (F427), a solvent-exposed residue in the lumen of the pore, was identified earlier as being crucial for the transport function of PA. The seven F427 residues were shown in electrophysiological studies to form a clamp that catalyzes protein translocation through the pore. Here, we demonstrate by a variety of tests that certain F427 mutations also profoundly inhibit the conformational transition of the heptameric PA prepore to the pore and thereby block pore formation in membranes. Lysine, arginine, aspartic acid, or glycine at position 427 strongly inhibited this acidic pH-induced conformational transition, whereas histidine, serine, and threonine had virtually no effect on this step, but inhibited translocation instead. Thus, it is possible to inhibit pore formation or translocation selectively, depending on the choice of the side chain at position 427; and the net inhibition of the PA transport function by any given F427 mutation is the product of its effects on both steps. Mutations inhibiting either or both steps elicited a strong dominant-negative phenotype. These findings demonstrate the dual functions of F427 and underline its central role in transporting the enzymatic moieties of anthrax toxin across membranes.

Photolysis of Indole-Containing Mycotoxins to Fluorescent Products

USDA-ARS?s Scientific Manuscript database

Photochemical reaction of the non-fluorescent mycotoxin cyclopiazonic acid (CPA) to fluorescent products was recently reported. Because CPA contains an indole moiety, believed to contribute to the fluorescence, it was of interest to determine whether the effect might be more generally applicable to ...

The antimicrobial efficacy and structure activity relationship of novel carbohydrate fatty acid derivatives against Listeria spp. and food spoilage microorganisms.

PubMed

Nobmann, Patricia; Smith, Aoife; Dunne, Julie; Henehan, Gary; Bourke, Paula

2009-01-15

Novel mono-substituted carbohydrate fatty acid (CFA) esters and ethers were investigated for their antibacterial activity against a range of pathogenic and spoilage bacteria focussing on Listeria monocytogenes. Carbohydrate derivatives with structural differences enable comparative studies on the structure/activity relationship for antimicrobial efficacy and mechanism of action. The antimicrobial efficacy of the synthesized compounds was compared with commercially available compounds such as monolaurin and monocaprylin, as well as the pure free fatty acids, lauric acid and caprylic acid, which have proven antimicrobial activity. Compound efficacy was compared using an absorbance based broth microdilution assay to determine the minimum inhibitory concentration (MIC), increase in lag phase and decrease in maximum growth rate. Among the carbohydrate derivatives synthesized, lauric ether of methyl alpha-d-glucopyranoside and lauric ester of methyl alpha-d-mannopyranoside showed the highest growth-inhibitory effect with MIC values of 0.04 mM, comparable to monolaurin. CFA derivatives were generally more active against Gram positive bacteria than Gram negative bacteria. The analysis of both ester and ether fatty acid derivatives of the same carbohydrate, in tandem with alpha and beta configuration of the carbohydrate moiety suggest that the carbohydrate moiety is involved in the antimicrobial activity of the fatty acid derivatives and that the nature of the bond also has a significant effect on efficacy, which requires further investigation. This class of CFA derivatives has great potential for developing antibacterial agents relevant to the food industry, particularly for control of Listeria or other Gram-positive pathogens.

Protective effect and relation structure-activity of nonivamide and iododerivatives in several models of lipid oxidation.

PubMed

Rosa, Antonella; Appendino, Giovanni; Melis, M Paola; Deiana, Monica; Atzeri, Angela; Alessandra, Incani; Minassi, Alberto; Dessì, M Assunta

2009-07-15

The introduction of an iodine atom on the vanillyl moiety of nonivamide causes a switch in the vanilloid activity (TRPV1 antagonism versus TRPV1 desensitization) and nullifies the aversive properties of capsaicinoids. In the present study we investigated the effect of iodination in the vanillyl moiety on the antioxidant activity of capsaicinoids. To this aim, we have compared the protective effects of nonivamide and three iododerivatives, 2-iodononivamide (2IN), 5-iodononivamide (5IN), and 6-iodononivamide (6IN) in a series of in vitro models of lipid oxidation, namely the autoxidation and the FeCl(3)-mediated oxidation of linoleic acid at 37 degrees C and the thermal (140 degrees C), solvent-free oxidation of cholesterol. All tested compounds could protect linoleic acid and cholesterol against oxidative degradation, the order of potency being: nonivamide>5IN>6IN approximately 2IN. Our results show that, in general, the introduction of an iodine atom on the vanillyl moiety of nonivamide causes a decrease in the antioxidant activity, and this effect is sensitive to the position of iodine on the aromatic ring, with 5IN substantially retaining the efficacy of nonivamide to protect linoleic and cholesterol against free radical attack. Moreover, the pre-treatment with 5IN, at noncytotoxic concentrations, significantly preserved LDL from Cu(2+)-induced oxidative damage at 37 degrees C for 2h, inhibiting the reduction of polyunsaturated fatty acids and cholesterol and the increase of their oxidative products. The results of the present work suggest that 5IN exerts useful antioxidant properties in different in vitro systems of lipid peroxidation. This, coupled to its lacks of pungency and TRPV1 inhibiting properties, qualifies this phenolic compound as an attractive candidate for further investigations in vivo.

Direct and irreversible inhibition of cyclooxygenase-1 by nitroaspirin (NCX 4016).

PubMed

Corazzi, Teresa; Leone, Mario; Maucci, Raffaella; Corazzi, Lanfranco; Gresele, Paolo

2005-12-01

Benzoic acid, 2-(acetyl-oxy)-3-[(nitrooxy)methyl]phenyl ester (NCX 4016), a new drug made by an aspirin molecule linked, through a spacer, to a nitric oxide (NO)-donating moiety, is now under clinical testing for the treatment of atherothrombotic conditions. Aspirin exerts its antithrombotic activity by irreversibly inactivating platelet cyclooxygenase (COX)-1. NCX 4016 in vivo undergoes metabolism into deacetylated and/or denitrated metabolites, and it is not known whether NCX 4016 needs to liberate aspirin to inhibit COX-1, or whether it can block it as a whole molecule. The aim of our study was to evaluate the effects of NCX 4016 and its analog or metabolites on platelet COX-1 and whole blood COX-2 and on purified ovine COX (oCOX)-1 and oCOX-2. In particular, we have compared the mechanism by which NCX 4016 inhibits purified oCOX enzymes with that of aspirin using a spectrophotometric assay. All the NCX 4016 derivatives containing acetylsalicylic acid inhibited the activity of oCOX-1 and oCOX-2, whereas the deacetylated metabolites and the nitric oxide-donating moiety were inactive. Dialysis experiments showed that oCOX-1 inhibition by NCX 4016, similar to aspirin, is irreversible. Reversible COX inhibitors (indomethacin) or salicylic acid incubated with the enzyme before NCX 4016 prevent the irreversible inhibition of oCOX-1 by NCX 4016 as well as by aspirin. In conclusion, our data show that NCX 4016 acts as a direct and irreversible inhibitor of COX-1 and that the presence of a spacer and NO-donating moiety in the molecule slows the kinetics of COX-1 inhibition by NCX 4016, compared with aspirin.

Discovery, synthesis, and pharmacological evaluation of spiropiperidine hydroxamic acid based derivatives as structurally novel histone deacetylase (HDAC) inhibitors.

PubMed

Varasi, Mario; Thaler, Florian; Abate, Agnese; Bigogno, Chiara; Boggio, Roberto; Carenzi, Giacomo; Cataudella, Tiziana; Dal Zuffo, Roberto; Fulco, Maria Carmela; Rozio, Marco Giulio; Mai, Antonello; Dondio, Giulio; Minucci, Saverio; Mercurio, Ciro

2011-04-28

New spiro[chromane-2,4'-piperidine] and spiro[benzofuran-2,4'-piperidine] hydroxamic acid derivatives as HDAC inhibitors have been identified by combining privileged structures with a hydroxamic acid moiety as zinc binding group. The compounds were evaluated for their ability to inhibit nuclear extract HDACs and for their in vitro antiproliferative activity on different tumor cell lines. This work resulted in the discovery of spirocycle 30d that shows good oral bioavailability and tumor growth inhibition in an HCT-116 murine xenograft model.

Design and synthesis of aryl ether and sulfone hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.

PubMed

Pabba, Chittari; Gregg, Brian T; Kitchen, Douglas B; Chen, Zhen Jia; Judkins, Angela

2011-01-01

A series of novel hydroxamic acid based histone deacetylases (HDAC) inhibitors with aryl ether and aryl sulfone residues at the terminus of a substituted, unsaturated 5-carbon spacer moiety have been synthesized for the first time and evaluated. Compounds with meta- and para-substitution on the aryl ring of ether hydroxamic acids 19c, 20c, 19e, 19f and 19g are potent HDAC inhibitors with activities at low nanomolar levels. Copyright © 2010 Elsevier Ltd. All rights reserved.

Antioxidant activity of commercial food grade tannins exemplified in a wine model.

PubMed

Ricci, Arianna; Olejar, Kenneth J; Parpinello, Giuseppina P; Mattioli, Alessia U; Teslić, Nemanja; Kilmartin, Paul A; Versari, Andrea

2016-12-01

Although commercial tannins are widely used in foods and beverages, an improved understanding of the structure and composition of vegetable tannins is needed to promote the exploitation of agri-food by-products and waste and their valorisation in more sustainable industrial applications. This study aims to characterise the phytochemical composition and antioxidant activity of 13 food grade tannins using multiple analytical approaches, including spectrophotometry and HPLC-ECD to determine the amount of targeted polyphenolic compounds. Moreover, the antioxidant activity of tannins was assessed in terms of radical scavenging activity (DPPH• assay), reducing power (FRAP assay), and redox properties (cyclic voltammetry, CV). A statistical univariate and multivariate correlation analysis was performed on 17 parameters including tannin content (range: 0.71-1.62 mM), gallic acid, (+)-catechin, syringic acid and (‒)-epicatechin. The compositional profile of tannins was related to their chemical moiety, antioxidant activity and the botanical origin of the extracts. In particular, the CV signal at 500 mV was highly correlated with DPPH• value due to the catechol ring of flavonoids and trigalloyl moieties of gallic acid-based compounds. Practical examples of tannins application in winemaking are discussed.

Structure-activity relationships of lanostane-type triterpenoids from Ganoderma lingzhi as α-glucosidase inhibitors.

PubMed

Fatmawati, Sri; Kondo, Ryuichiro; Shimizu, Kuniyoshi

2013-11-01

A series of lanostane-type triterpenoids, identified as ganoderma alcohols and ganoderma acids, were isolated from the fruiting body of Ganoderma lingzhi. Some of these compounds were confirmed as active inhibitors of the in vitro human recombinant aldose reductase. This paper aims to explain the structural requirement for α-glucosidase inhibition. Our structure-activity studies of ganoderma alcohols showed that the OH substituent at C-3 and the double-bond moiety at C-24 and C-25 are necessary to increase α-glucosidase inhibitory activity. The structure-activity relationships of ganoderma acids revealed that the OH substituent at C-11 is an important feature and that the carboxylic group in the side chain is essential for the recognition of α-glucosidase inhibitory activity. Moreover, the double-bond moiety at C-20 and C-22 in the side chain and the OH substituent at C-3 of ganoderma acids improve α-glucosidase inhibitory activity. These results provide an approach with which to consider the structural requirements of lanostane-type triterpenoids from G. lingzhi. An understanding of these requirements is considered necessary in order to improve a new type of α-glucosidase inhibitor. Copyright © 2013 Elsevier Ltd. All rights reserved.

Design and synthesis of novel 2-(indol-5-yl)thiazole derivatives as xanthine oxidase inhibitors.

PubMed

Song, Jeong Uk; Choi, Sung Pil; Kim, Tae Hun; Jung, Cheol-Kyu; Lee, Joo-Youn; Jung, Sang-Hun; Kim, Geun Tae

2015-03-15

Xanthine oxidase (XO) inhibitors have been widely used for the treatment of gout. Indole rings are frequently used as active scaffold in designing inhibitors for enzymes. Herein, we describe the structure-activity relationship for novel xanthine oxidase inhibitors based on indole scaffold. A series of novel tri-substituted 2-(indol-5-yl)thiazole derivatives were synthesized, and their in vitro inhibitory activities against xanthine oxidase and in vivo efficacy lowering uric acid level in blood were measured. Among them, 2-(3-cyano-2-isopropylindol-5-yl)-4-methylthiazole-5-carboxylic acid exhibits the most potent XO inhibitory activity (IC50 value: 3.5nM) and the excellent plasma uric acid lowering activity. Study of structure activity relationship indicated that hydrophobic moiety (e.g., isopropyl) at 1-position and electron withdrawing group (e.g., CN) at 3-position of indole ring and small hydrophobic group (CH3) at 4-position of the thiazole ring enhanced the XO inhibitory activity. Hydrophobic substitution such as isopropyl at 1-position of the indole moiety without any substitution at 2-position has an essential role for enhancing bioavailability and therefore for high in vivo efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N-benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer's disease.

PubMed

Lan, Jin-Shuai; Hou, Jian-Wei; Liu, Yun; Ding, Yue; Zhang, Yong; Li, Ling; Zhang, Tong

2017-12-01

A novel family of cinnamic acid derivatives has been developed to be multifunctional cholinesterase inhibitors against AD by fusing N-benzyl pyridinium moiety and different substituted cinnamic acids. In vitro studies showed that most compounds were endowed with a noteworthy ability to inhibit cholinesterase, self-induced Aβ (1-42) aggregation, and to chelate metal ions. Especially, compound 5l showed potent cholinesterase inhibitory activity (IC 50 , 12.1 nM for eeAChE, 8.6 nM for hAChE, 2.6 μM for eqBuChE and 4.4 μM for hBuChE) and the highest selectivity toward AChE over BuChE. It also showed good inhibition of Aβ (1-42) aggregation (64.7% at 20 μM) and good neuroprotection on PC12 cells against amyloid-induced cell toxicity. Finally, compound 5l could penetrate the BBB, as forecasted by the PAMPA-BBB assay and proved in OF1 mice by ex vivo experiments. Overall, compound 5l seems to be a promising lead compound for the treatment of Alzheimer's diseases.

Defective Pollen Wall 2 (DPW2) Encodes an Acyl Transferase Required for Rice Pollen Development1[OPEN

PubMed Central

Shi, Jianxin; Rautengarten, Carsten; Yang, Li; Uzair, Muhammad; Zhu, Lu; Luo, Qian; An, Gynheung; Waßmann, Fritz

2017-01-01

Aliphatic and aromatic lipids are both essential structural components of the plant cuticle, an important interface between the plant and environment. Although cross links between aromatic and aliphatic or other moieties are known to be associated with the formation of leaf cutin and root and seed suberin, the contribution of aromatic lipids to the biosynthesis of anther cuticles and pollen walls remains elusive. In this study, we characterized the rice (Oryza sativa) male sterile mutant, defective pollen wall 2 (dpw2), which showed an abnormal anther cuticle, a defective pollen wall, and complete male sterility. Compared with the wild type, dpw2 anthers have increased amounts of cutin and waxes and decreased levels of lipidic and phenolic compounds. DPW2 encodes a cytoplasmically localized BAHD acyltransferase. In vitro assays demonstrated that recombinant DPW2 specifically transfers hydroxycinnamic acid moieties, using ω-hydroxy fatty acids as acyl acceptors and hydroxycinnamoyl-CoAs as acyl donors. Thus, The cytoplasmic hydroxycinnamoyl-CoA:ω-hydroxy fatty acid transferase DPW2 plays a fundamental role in male reproduction via the biosynthesis of key components of the anther cuticle and pollen wall. PMID:27246096

Defective Pollen Wall 2 ( DPW2 ) Encodes an Acyl Transferase Required for Rice Pollen Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Dawei; Shi, Jianxin; Rautengarten, Carsten

Aliphatic and aromatic lipids are both essential structural components of the plant cuticle, an important interface between the plant and environment. Although cross links between aromatic and aliphatic or other moieties are known to be associated with the formation of leaf cutin and root and seed suberin, the contribution of aromatic lipids to the biosynthesis of anther cuticles and pollen walls remains elusive. In this study, we characterized the rice (Oryza sativa) male sterile mutant, defective pollen wall 2 (dpw2), which showed an abnormal anther cuticle, a defective pollen wall, and complete male sterility. Compared with the wild type, dpw2more » anthers have increased amounts of cutin and waxes and decreased levels of lipidic and phenolic compounds. DPW2 encodes a cytoplasmically localized BAHD acyltransferase. In vitro assays demonstrated that recombinant DPW2 specifically transfers hydroxycinnamic acid moieties, using v-hydroxy fatty acids as acyl acceptors and hydroxycinnamoyl-CoAs as acyl donors. Thus, The cytoplasmic hydroxycinnamoyl-CoA:v-hydroxy fatty acid transferase DPW2 plays a fundamental role in male reproduction via the biosynthesis of key components of the anther cuticle and pollen wall.« less

Sugar-Responsive Layer-by-Layer Film Composed of Phenylboronic Acid-Appended Insulin and Poly(vinyl alcohol).

PubMed

Takei, Chihiro; Ohno, Yui; Seki, Tomohiro; Miki, Ryotaro; Seki, Toshinobu; Egawa, Yuya

2018-01-01

Previous studies have shown that reversible chemical bond formation between phenylboronic acid (PBA) and 1,3-diol can be utilized as the driving force for the preparation of layer-by-layer (LbL) films. The LbL films composed of a PBA-appended polymer and poly(vinyl alcohol) (PVA) disintegrated in the presence of sugar. This type of LbL films has been recognized as a promising approach for sugar-responsive drug release systems, but an issue preventing the practical application of LbL films is combining them with insulin. In this report, we have proposed a solution for this issue by using PBA-appended insulin as a component of the LbL film. We prepared two kinds of PBA-appended insulin derivatives and confirmed that they retained their hypoglycemic activity. The LbL films composed of PBA-appended insulin and PVA were successfully prepared through reversible chemical bond formation between the boronic acid moiety and the 1,3-diol of PVA. The LbL film disintegrated upon treatment with sugars. Based on the results presented herein, we discuss the suitability of the PBA moiety with respect to hypoglycemic activity, binding ability, and selectivity for D-glucose.

[Synthesis and physico-chemical characterisation of some new derivatives of rutoside and clofibric acid].

PubMed

Lupaşcu, D; Profire, Lenuţa; Dănilă, Gh

2006-01-01

Fibrates are drugs with efficacy in reducing blood cholesterol levels and especially, triglyceride plasma levels. Unfortunately, fibrates have a poor water-solubility and showed some adverse reactions at long treatment. The objective of this study was to obtain some new clofibric acid derivatives with rutin; some of these compounds contain a guanidine moiety, known as effective at cardiovascular level. All the compounds are soluble in water.

Conductive polymeric compositions for lithium batteries

DOEpatents

Angell, Charles A [Mesa, AZ; Xu, Wu [Tempe, AZ

2009-03-17

Novel chain polymers comprising weakly basic anionic moieties chemically bound into a polyether backbone at controllable anionic separations are presented. Preferred polymers comprise orthoborate anions capped with dibasic acid residues, preferably oxalato or malonato acid residues. The conductivity of these polymers is found to be high relative to that of most conventional salt-in-polymer electrolytes. The conductivity at high temperatures and wide electrochemical window make these materials especially suitable as electrolytes for rechargeable lithium batteries.

Oxidation of ferrocene by thiocyanic acid in the presence of ammonium oxalate

NASA Astrophysics Data System (ADS)

Ruslin, Farah bt; Yamin, Bohari M.

2014-09-01

A flake-like crystalline salt was obtained from the reaction of ferrocene, oxalic acid and ammonium thiocyanate in ethanol The elemental analysis and spectroscopic data were in agreement with the preliminary X-ray molecular structure. The compound consists of four ferrocenium moieties and a counter anion consisting of two (tetraisothiocyanato)iron(III) linked by an oxalato bridging group in such a way that both iron central atoms adopt octahedral geometries.

A new approach to the synthesis of monomers and polymers incorporating furan/maleimide Diels-Alder adducts

NASA Astrophysics Data System (ADS)

Banella, Maria Barbara; Gioia, Claudio; Vannini, Micaela; Colonna, Martino; Celli, Annamaria; Gandini, Alessandro

2016-05-01

The Diels-Alder reaction between furan and maleimide moieties is a well-known and widely used strategy to build bio-based macromolecular structures with peculiar properties. The furan-maleimide adducts are thermally reversible because they can be broken above about 120°C and recombined at lower temperatures. At the moment only the monomers exhibiting the furan or the maleimide moieties on their extremity are used in order to get linear or cross-linked polymeric structures. The innovative idea described here consists in using a monomer bearing two carboxylic acidic groups on its extremities and a furan-maleimide Diels-Alder adduct within its structure. This monomer can give rise to classical polycondensation reactions leading to polymers. These polymers (which are polyesters in the present case) can be broken at high temperatures in correspondence of the furane-maleimide Diels-Alder adduct leading to segments exhibiting furan or maleimide moieties at their extremities, which at lower temperature recombine leading to random or block copolymers.

Analysis of the photophysical properties of zearalenone using density functional theory

USDA-ARS?s Scientific Manuscript database

The intrinsic photophysical properties of the resorcylic acid moiety of zearalenone offer a convenient label free method to determine zearalenone levels in contaminated agricultural products. Density functional theory and steady-state fluorescence methods were applied to investigate the role of stru...

Facile synthesis of the cyclohexane fragment of enacloxins, a series of antibiotics isolated from Frateuria sp. W-315.

PubMed

Saito, Aki; Igarashi, Wataru; Furukawa, Hiroyuki; Yamada, Teiko; Kuwahara, Shigefumi; Kiyota, Hiromasa

2014-01-01

An efficient and good yield synthesis of the cyclohexane moiety of enacyloxins, a series of antibiotics isolated from Frateuria sp. W-315, was achieved from d-quinic acid using a successive Barton-McCombie deoxygenation.

The complete microspeciation of ovothiol A disulfide: a hexabasic symmetric biomolecule.

PubMed

Mirzahosseini, Arash; Orgován, Gábor; Tóth, Gergő; Hosztafi, Sándor; Noszál, Béla

2015-03-25

The site-specific acid-base properties of ovothiol A disulfide (OvSSOv), the smallest hexabasic multifunctional biomolecule with complex interdependent moieties, were studied with (1)H NMR-pH and potentiometric titrations. The unprecedented complexity of the protonation microequilibria could be overcome by taking into account the mirror-image molecular symmetry, synthesizing and studying auxiliary model compounds and developing a custom-tailored evaluation method. The amino, imidazole, and carboxylate moieties are quantified in terms of 192 microscopic protonation constants and 64 microspecies, 96 and 36 of which are chemically different ones, respectively. Nine pairwise interactivity parameters also characterize the OvSSOv-proton system at the level of molecular subunits. These data allow understanding and influencing the co-dependent acid-base and redox properties of the highly complex OvSH-OvSSOv and related thiol-disulfide systems, which provide protection against oxidative stress. This work is the first complete microspeciation of a hexabasic molecule. Copyright © 2014 Elsevier B.V. All rights reserved.

Method for loading lipid like vesicles with drugs of other chemicals

DOEpatents

Mehlhorn, R.J.

1998-06-09

A method for accumulating drugs or other chemicals within synthetic, lipid-like vesicles by means of a pH gradient imposed on the vesicles just prior to use is described. The method is suited for accumulating molecules with basic or acid moieties which are permeable to the vesicles membranes in their uncharged form and for molecules that contain charge moieties that are hydrophobic ions and can therefore cross the vesicle membranes in their charged form. The method is advantageous over prior art methods for encapsulating biologically active materials within vesicles in that is achieves very high degrees of loading with simple procedures that are economical and require little technical expertise, furthermore kits which can be stored for prolonged periods prior to use without impairment of the capacity to achieve drug accumulation are described. A related application of the method consists of using this technology to detoxify animals that have been exposed to poisons with basic, weak acid or hydrophobic charge groups within their molecular structures. 2 figs.

Method for loading lipid like vesicles with drugs of other chemicals

DOEpatents

Mehlhorn, Rolf Joachim

1998-01-01

A method for accumulating drugs or other chemicals within synthetic, lipid-like vesicles by means of a pH gradient imposed on the vesicles just prior to use is described. The method is suited for accumulating molecules with basic or acid moieties which are permeable to the vesicles membranes in their uncharged form and for molecules that contain charge moieties that are hydrophobic ions and can therefore cross the vesicle membranes in their charged form. The method is advantageous over prior art methods for encapsulating biologically active materials within vesicles in that is achieves very high degrees of loading with simple procedures that are economical and require little technical expertise, furthermore kits which can be stored for prolonged periods prior to use without impairment of the capacity to achieve drug accumulation are described. A related application of the method consists of using this technology to detoxify animals that have been exposed to poisons with basic, weak acid or hydrophobic charge groups within their molecular structures.

Modified melanocortin tetrapeptide Ac-His-dPhe-Arg-Trp-NH at the arginine side chain with ureas and thioureas.

PubMed

Joseph, C G; Sorensen, N B; Wood, M S; Xiang, Z; Moore, M C; Haskell-Luevano, C

2005-11-01

The Ac-His-dPhe-Arg-Trp-NH2 tetrapeptide is a nonselective melanocortin agonist and replacement of Arg in the tetrapeptide with acidic, basic or neutral amino acids results in reduced potency at the melanocortin receptor (MCR) isoforms (MC1R and MC3-5R). To determine the importance of the positive charge and the guanidine moiety for melanocortin activity, a series of urea- and thiourea-substituted tetrapeptides were designed. Replacement of Arg with Lys or ornithine reduced agonist activity at the mouse mMC1 and mMC3-5 receptors, thus supporting the hypothesis that the guanidine moiety is important for receptor potency, particularly at the MC3-5 receptors. The Arg side chain-modified tetrapeptides examined in this study include substituted phenyl, naphthyl, and aliphatic urea and thiourea residues using a Lys side-chain template. These ligands elicit full-agonist pharmacology at the mouse MCRs examined in this study.

Methylocystis strain SB2 materials and methods

DOEpatents

Semrau, Jeremy D; Gallagher, Warren; Yoon, Sukhwan; Im, Jeongdae; DiSpririto, Alan A; Lee, Sung-Woo; Hartsel, Scott; McEllistrem, Marcus T

2014-01-14

The present disclosures provides isolated or purified compounds, each of which bind to a metal atom. Generally, the compounds are small in size (e.g., molecular weight of less than about 1 kDa) and peptidic in nature, inasmuch as the compounds comprise amino acids. In some embodiments, the compound comprises a structure of Formula I; M.sub.1-P.sub.1-M.sub.2-P.sub.2 wherein each of P.sub.1 and P.sub.2 is a peptide comprising at least two amino acids, M.sub.1 is a first metal binding moiety comprising a substituted imidazolone ring, M.sub.2 is a second metal binding moiety comprising a substituted oxazolone ring, and wherein M.sub.1 and M.sub.2 bind to a single metal atom. Also provided are related complexes, conjugates, cells which synthesize the compounds of the present disclosures, substantially homogenous cultures thereof, kits and compositions, and methods of making or using the materials of the present disclosures.

Glycosylinositolphosphoceramides in Aspergillus fumigatus.

PubMed

Simenel, Catherine; Coddeville, Bernadette; Delepierre, Muriel; Latgé, Jean-Paul; Fontaine, Thierry

2008-01-01

Fungal glycosylinositolphosphoceramides (GIPCs) are involved in cell growth and fungal-host interactions. In this study, six GIPCs from the mycelium of the human pathogen Aspergillus fumigatus were purified and characterized using Q-TOF mass spectrometry and 1H, 13C, and 31P NMR. All structures have the same inositolphosphoceramide moiety with the presence of a C(18:0)-phytosphingosine conjugated to a 2-hydroxylated saturated fatty acid (2-hydroxy-lignoceric acid). The carbohydrate moiety defines two types of GIPC. The first, a mannosylated zwitterionic glycosphingolipid contains a glucosamine residue linked in alpha1-2 to an inositol ring that has been described in only two other fungal pathogens. The second type of GIPC presents an alpha-Manp-(1-->3)-alpha-Manp-(1-->2)-IPC common core. A galactofuranose residue is found in four GIPC structures, mainly at the terminal position via a beta1-2 linkage. Interestingly, this galactofuranose residue could be substituted by a choline-phosphate group, as observed only in the GIPC of Acremonium sp., a plant pathogen.

Method of detoxifying animal suffering from overdose

DOEpatents

Mehlhorn, Rolf J.

1997-01-01

A method for accumulating drugs or other chemicals within synthetic, lipid-like vesicles by means of a pH gradient imposed on the vesicles just prior to use is described. The method is suited for accumulating molecules with basic or acid moieties which are permeable to the vesicles membranes in their uncharged form and for molecules that contain charge moieties that are hydrophobic ions and can therefore cross the vesicle membranes in their charged form. The method is advantageous over prior art methods for encapsulating biologically active materials within vesicles in that it achieves very high degrees of loading with simple procedures that are economical and require little technical expertise, furthermore kits which can be stored for prolonged periods prior to use without impairment of the capacity to achieve drug accumulation are described. A related application of the method consists of using this technology to detoxify animals that have been exposed to poisons with basic, weak acid or hydrophobic charge groups within their molecular structure.

A Search for CD36 Ligands from Flavor Volatiles in Foods with an Aldehyde Moiety: Identification of Saturated Aliphatic Aldehydes with 9-16 Carbon Atoms as Potential Ligands of the Receptor.

PubMed

Tsuzuki, Satoshi; Amitsuka, Takahiko; Okahashi, Tatsuya; Kimoto, Yusaku; Inoue, Kazuo

2017-08-09

Volatile compounds with an aldehyde moiety such as (Z)-9-octadecenal are potential ligands for cluster of differentiation 36 (CD36), a transmembrane receptor that has recently been shown to play a role in mammalian olfaction. In this study, by performing an assay using a peptide mimic of human CD36, we aimed to discover additional ligands for the receptor from volatiles containing a single aldehyde group commonly found in human foods. Straight-chain, saturated aliphatic aldehydes with 9-16 carbons exhibited CD36 ligand activities, albeit to varying degrees. Notably, the activities of tridecanal and tetradecanal were higher than that of oleic acid, the most potent ligand among the fatty acids tested. Among the aldehydes other than aliphatic aldehydes, only phenylacetaldehyde showed a weak activity. These findings make a contribution to our knowledge of recognition mechanisms for flavor volatiles in foods with an aldehyde group.

Synthesis of zinc-crosslinked thiolated alginic acid beads and their in vitro evaluation as potential enteric delivery system with folic acid as model drug.

PubMed

Taha, M O; Aiedeh, K M; Al-Hiari, Y; Al-Khatib, H

2005-10-01

The aim of this study is to explore the potential of synthetic modifications of alginic acid as a method to enhance the stability of its complexes with divalent cations under physiological conditions. A fraction of algin's carboxylic acid moieties was substituted with thiol groups to different substitution degrees through conjugating alginate to cysteine to produce alginate-cysteine (AC) conjugates. Infrared spectrophotometry and iodometry were used to characterize the resulting polymeric conjugates in terms of structure and degree of substitution. Moreover, zinc ions were used to crosslink the resulting AC polymers. Folic acid loaded beads were prepared from Zinc-crosslinked AC polymers (AC-Zn) of different cysteine substitution degrees. The generated beads were then investigated in vitro for their capacity to modify folic acid release. AC-Zn polymeric beads resisted drug release under acidic conditions (pH 1.0). However, upon transfer to a phosphate buffer solution (pH 7.0) they released most of their contents almost immediately. This change in drug release behavior is most probably due to the sequestering of zinc cations by phosphate ions within the buffer solution to form insoluble chelates and, to a lesser extent, the ionization of the carboxylic acid and thiol moieties. Removal of zinc ions from the polymeric matrix seems to promote polymeric disintegration and subsequent drug release. A similar behavior is expected in vivo due to the presence of natural zinc sequestering agents in the intestinal fluids. AC-Zn polymers provided a novel approach for enteric drug delivery as drug release from these matrices complied with the USP specifications for enteric dosage forms.

Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid short- and branched-chain alkyl esters biodiesel.

PubMed

Teo, Wei Suong; Ling, Hua; Yu, Ai-Qun; Chang, Matthew Wook

2015-01-01

Biodiesel is a mixture of fatty acid short-chain alkyl esters of different fatty acid carbon chain lengths. However, while fatty acid methyl or ethyl esters are useful biodiesel produced commercially, fatty acid esters with branched-chain alcohol moieties have superior fuel properties. Crucially, this includes improved cold flow characteristics, as one of the major problems associated with biodiesel use is poor low-temperature flow properties. Hence, microbial production as a renewable, nontoxic and scalable method to produce fatty acid esters with branched-chain alcohol moieties from biomass is critical. We engineered Saccharomyces cerevisiae to produce fatty acid short- and branched-chain alkyl esters, including ethyl, isobutyl, isoamyl and active amyl esters using endogenously synthesized fatty acids and alcohols. Two wax ester synthase genes (ws2 and Maqu_0168 from Marinobacter sp.) were cloned and expressed. Both enzymes were found to catalyze the formation of fatty acid esters, with different alcohol preferences. To boost the ability of S. cerevisiae to produce the aforementioned esters, negative regulators of the INO1 gene in phospholipid metabolism, Rpd3 and Opi1, were deleted to increase flux towards fatty acyl-CoAs. In addition, five isobutanol pathway enzymes (Ilv2, Ilv5, Ilv3, Aro10, and Adh7) targeted into the mitochondria were overexpressed to enhance production of alcohol precursors. By combining these engineering strategies with high-cell-density fermentation, over 230 mg/L fatty acid short- and branched-chain alkyl esters were produced, which is the highest titer reported in yeast to date. In this work, we engineered the metabolism of S. cerevisiae to produce biodiesels in the form of fatty acid short- and branched-chain alkyl esters, including ethyl, isobutyl, isoamyl and active amyl esters. To our knowledge, this is the first report of the production of fatty acid isobutyl and active amyl esters in S. cerevisiae. Our findings will be useful for engineering S. cerevisiae strains toward high-level and sustainable biodiesel production.

Simple Fabrication of Gd(III)-DTPA-Nanodiamond Particles by Chemical Modification for Use as Magnetic Resonance Imaging (MRI) Contrast Agent

NASA Astrophysics Data System (ADS)

Nakamura, Takako; Ohana, Tsuguyori; Yabuno, Hajime; Kasai, Rumiko; Suzuki, Tetsuya; Hasebe, Terumitsu

2013-01-01

We have developed a simple and useful process for fabricating nanodiamond (ND) particles modified with an organogadolinium moiety by chemical modification for their use as a magnetic resonance imaging (MRI) contrast agent. The introduction of the organogadolinium moiety on the surface of the ND particles was performed by the condensation of ND and diethylenetriaminepentaacetic acid (DTPA) followed by treatment with GdCl3. The modified surfaces were evaluated by X-ray photoelectron spectroscopy, diffuse reflectance Fourier transform infrared spectroscopy, mass spectroscopy, and inductively coupled plasma atomic emission spectroscopy analyses. MRI experiments on the Gd-DTPA-ND particles indicated their high signal intensity on T1-weighted images.

Stereoselective synthesis of nicotinamide beta-riboside and nucleoside analogs.

PubMed

Franchetti, Palmarisa; Pasqualini, Michela; Petrelli, Riccardo; Ricciutelli, Massimo; Vita, Patrizia; Cappellacci, Loredana

2004-09-20

The beta-anomers of N-ribofuranosylnicotine-3-carboxamide (beta-NAR) and its nicotinic acid analog (beta-NaR) were obtained by stereoselective synthesis via glycosylation of the presilylated bases under Vorbruggen's protocol. A NAR analog, methylated in position 3 of the ribosylic moiety, is also reported.

Improvement of Pro-Oxidant Capacity of Protocatechuic Acid by Esterification

PubMed Central

Zeraik, Maria Luiza; Petrônio, Maicon S.; Coelho, Dyovani; Regasini, Luis Octavio; Silva, Dulce H. S.; da Fonseca, Luiz Marcos; Machado, Sergio A. S.; Bolzani, Vanderlan S.; Ximenes, Valdecir F.

2014-01-01

Pro-oxidant effects of phenolic compounds are usually correlated to the one-electron redox potential of the phenoxyl radicals. Here we demonstrated that, besides their oxidizability, hydrophobicity can also be a decisive factor. We found that esterification of protocatechuic acid (P0) provoked a profound influence in its pro-oxidant capacity. The esters bearing alkyl chains containing two (P2), four (P4) and seven (P7) carbons, but not the acid precursor (P0), were able to exacerbate the oxidation of trolox, α-tocopherol and rifampicin. This effect was also dependent on the catechol moiety, since neither gallic acid nor butyl gallate showed any pro-oxidant effects. A comparison was also made with apocynin, which is well-characterized regarding its pro-oxidant properties. P7 was more efficient than apocynin regarding co-oxidation of trolox. However, P7 was not able to co-oxidize glutathione and NADH, which are targets of the apocynin radical. A correlation was found between pro-oxidant capacity and the stability of the radicals, as suggested by the intensity of the peak current in the differential pulse voltammetry experiments. In conclusion, taking into account that hydroquinone and related moieties are frequently found in biomolecules and quinone-based chemotherapeutics, our demonstration that esters of protocatechuic acid are specific and potent co-catalysts in their oxidations may be very relevant as a pathway to exacerbate redox cycling reactions, which are usually involved in their biological and pharmacological mechanisms of action. PMID:25340774

Chemical-modification studies of a unique sialic acid-binding lectin from the snail Achatina fulica. Involvement of tryptophan and histidine residues in biological activity.

PubMed Central

Basu, S; Mandal, C; Allen, A K

1988-01-01

A unique sialic acid-binding lectin, achatininH (ATNH) was purified in single step from the haemolymph of the snail Achatina fulica by affinity chromatography on sheep submaxillary-gland mucin coupled to Sepharose 4B. The homogeneity was checked by alkaline gel electrophoresis, immunodiffusion and immunoelectrophoresis. Amino acid analysis showed that the lectin has a fairly high content of acidic amino acid residues (22% of the total). About 1.3% of the residues are half-cystine. The glycoprotein contains 21% carbohydrate. The unusually high content of xylose (6%) and fucose (2.7%) in this snail lectin is quite interesting. The protein was subjected to various chemical modifications in order to detect the amino acid residues and carbohydrate residues present in its binding sites. Modification of tyrosine and arginine residues did not affect the binding activity of ATNH; however, modification of tryptophan and histidine residues led to a complete loss of its biological activity. A marked decrease in the fluorescence emission was found as the tryptophan residues of ATNH were modified. The c.d. data showed the presence of an identical type of conformation in the native and modified agglutinin. The modification of lysine and carboxy residues partially diminished the biological activity. The activity was completely lost after a beta-elimination reaction, indicating that the sugars are O-glycosidically linked to the glycoprotein's protein moiety. This result confirms that the carbohydrate moiety also plays an important role in the agglutination property of this lectin. Images Fig. 3. PMID:3140796

10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki

Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductasemore » 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.« less

Synthesis and pharmacological evaluation of conformationally constrained glutamic acid higher homologues.

PubMed

Tamborini, Lucia; Cullia, Gregorio; Nielsen, Birgitte; De Micheli, Carlo; Conti, Paola; Pinto, Andrea

2016-11-15

Homologation of glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. In the present work, starting from two potent and selective unnatural amino acids previously developed by us, we investigated the effects on the activity/selectivity profile produced by a further increase in the distance between the amino acidic moiety and the distal carboxylate group. Interestingly, the insertion of an aromatic ring as a spacer produced a low micromolar affinity NMDA ligand that might represent a lead for the development of a new class of NMDA antagonists. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lipoic acid functionalized amino acids cationic lipids as gene vectors.

PubMed

Su, Rong-Chuan; Liu, Qiang; Yi, Wen-Jing; Zheng, Li-Ting; Zhao, Zhi-Gang

2016-10-01

A series of reducible cationic lipids 4a-4f with different amino acid polar-head groups were prepared. The novel lipid contains a hydrophobic lipoic acid (LA) moiety, which can be reduced under reductive conditions to release of the encapsulated plasmid DNA. The particle size, zeta potential and cellular uptake of lipoplexes formed with DNA, as well as the transfection efficacy (TE) were characterized. The TE of the cationic lipid based on arginine was especially high, and was 2.5times higher than that of a branched polyethylenimine in the presence of 10% serum. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ursolic Acid and Oleanolic Acid: Pentacyclic Terpenoids with Promising Anti-Inflammatory Activities.

PubMed

Kashyap, Dharambir; Sharma, Ajay; Tuli, Hardeep S; Punia, Sandeep; Sharma, Anil K

2016-01-01

Plant derived products are not only served as dietary components but also used to treat and prevent the inflammatory associated diseases like cancer. Among the natural products pentacyclic terpenoids including ursolic acid and oleanolic acid are considered as the promising anti-inflammatory therapeutic agents. The current review extensively discusses the anti-inflammatory therapeutic potential of these pentacyclic moieties along with their proposed mechanisms of action. Furthermore, the relevant patents have also been listed to present the health benefits of these promising therapeutic agents to pin down the inflammatory diseases. Expert opinion: Pentacyclic terpenoids are known to negatively down-regulate a variety of extracellular and intracellular molecular targets associated with disease progression. The major anti-inflammatory effects of these molecules have been found to be mediated via inactivation of NFkB, STAT3/6, Akt/mTOR pathways. A number of patents on UA & OA based moieties have been reported between 2010 and 2016. Still there have been only a few compounds which meet the need of sufficient hydro solubility and bioavailability along with higher anti-inflammatory activities. Thus, it is essential to develop novel derivatives of terpenpoids which may not only overcome the solubility issues but also may improve their therapeutic effects. In addition, scientific community may utilize nanotechnology based drug delivery systems so as to increase the bio-availability, selectivity and dosages related problems.

Stabilizing effect of propionic acid derivative of anthraquinone--polyamine conjugate incorporated into α-β chimeric oligonucleotides on the alternate-stranded triple helix.

PubMed

Moriguchi, Tomohisa; Azam, A T M Zafrul; Shinozuka, Kazuo

2011-06-15

Two types of anthraquinone conjugates were synthesized as non-nucleosidic oligonucleotide components. These include an anthraquinone derivative conjugated with 2,2-bis(hydroxymethyl)propionic acid and an anthraquinone--polyamine derivative conjugated with 2,2-bis(hydroxymethyl)propionic acid. The conjugates were successfully incorporated into the "linking-region" of the α-β chimeric oligonucleotides via phosphoramidite method as non-nucleosidic backbone units. The resultant novel α-β chimeric oligonucleotides possessed two diastereomers that were generated by the introduction of the anthraquinone conjugate with a stereogenic carbon atom. The isomers were successfully separated by a reversed-phase HPLC. UV-melting experiments revealed that both stereoisomers formed a substantially stable alternate-strand triple helix, irrespective of the stereochemistry of the incorporated non-nucleosidic backbone unit. However, the enhancing effect on thermal stability depended on the length of the alkyl linker connecting anthraquinone moiety and the propionic acid moiety. The sequence discrimination ability of the chimeric oligonucleotides toward mismatch target duplex was also examined. The T(m) values of the triplexes containing the mismatch target were substantially lower than the T(m) values of those containing the full-match target. The thermodynamic parameters (ΔH°, ΔS°, and ΔG°) required for the dissociation of the triplexes into the third strand and target duplex were also measured.

Development of Iron-Chelating Poly(ethylene terephthalate) Packaging for Inhibiting Lipid Oxidation in Oil-in-Water Emulsions.

PubMed

Johnson, David R; Tian, Fang; Roman, Maxine J; Decker, Eric A; Goddard, Julie M

2015-05-27

Foods such as bulk oils, salad dressings, and nutritionally fortified beverages that are susceptible to oxidative degradation are often packaged in poly(ethylene terephthalate) (PET) bottles with metal chelators added to the food to maintain product quality. In the present work, a metal-chelating active packaging material is designed and characterized, in which poly(hydroxamic acid) (PHA) metal-chelating moieties were grafted from the surface of PET. Biomimetic PHA groups were grafted in a two-step UV-initiated process without the use of a photoinitiator. Surface characterization of the films by attenuated total reflective Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM) suggested successful grafting and conversion of poly(hydroxyethyl acrylate) (PHEA) to PHA chelating moieties from the surface of PET. Colorimetric (ferrozine) and inductively coupled plasma mass spectroscopy (ICP-MS) assays demonstrated the ability of PET-g-PHA to chelate iron in a low-pH (3.0) environment containing a competitive metal chelator (citric acid). Lipid oxidation studies demonstrated the antioxidant activity of PET-g-PHA films in inhibiting iron-promoted oxidation in an acidified oil-in-water (O/W) emulsion model system (pH 3.0). Particle size and ζ-potential analysis indicated that the addition of PET-g-PHA films did not affect the physical stability of the emulsion system. This work suggests that biomimetic chelating moieties can be grafted from PET and effectively inhibit iron-promoted degradation reactions, enabling removal of metal-chelating additives from product formulations.

Closely related glycosylation patterns of recombinant human IL-2 expressed in a CHO cell line and natural IL-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vita, N.; Magazin, M.; Marchese, E.

We report here the study of the glycosylation pattern of human recombinant (r) IL2 expressed in a Chinese hamster ovary (CHO) cell line. The human rIL2 secreted by this high-producing recombinant CHO cell line was metabolically radiolabelled with (35S)-methionine, or with (3H)-glucosamine and (3H)-galactose, purified to homogeneity, and then characterized. The electrophoretic analysis of the (35S)-methionine-labelled proteins present in the culture medium of the CHO cell line showed that the rIL2 represents approximately 12% of the total secreted proteins. Furthermore, pulse-chase experiments showed that the glycosylated rIL2 is synthesized and secreted within 30 min. The point of attachment and themore » structure of the carbohydrate moiety of the rIL2 was determined by: amino-terminal sequencing and fingerprint analysis of the 3H-labelled rIL2, mass spectroscopy of the amino-terminal tryptic octapeptide, and carbohydrate analysis after enzymatic (Vibrio cholerae neuraminidase and Aspergillus oryzae beta-galactosidase) or sulfuric acid hydrolysis. The results indicate that the recombinant protein possesses a sugar moiety O-linked to the threonine residue at position 3 of the polypeptide chain, and that sialic acid, galactose and N-acetyl galactosamine are components of this carbohydrate moiety. Taken together these results suggest that the recombinant molecule is identical to natural IL2.« less

Characterization of the Amicetin Biosynthesis Gene Cluster from Streptomyces vinaceusdrappus NRRL 2363 Implicates Two Alternative Strategies for Amide Bond Formation

PubMed Central

Zhang, Gaiyun; Zhang, Haibo; Li, Sumei; Xiao, Ji; Zhang, Guangtao; Zhu, Yiguang; Niu, Siwen; Ju, Jianhua

2012-01-01

Amicetin, an antibacterial and antiviral agent, belongs to a group of disaccharide nucleoside antibiotics featuring an α-(1→4)-glycoside bond in the disaccharide moiety. In this study, the amicetin biosynthesis gene cluster was cloned from Streptomyces vinaceusdrappus NRRL 2363 and localized on a 37-kb contiguous DNA region. Heterologous expression of the amicetin biosynthesis gene cluster in Streptomyces lividans TK64 resulted in the production of amicetin and its analogues, thereby confirming the identity of the ami gene cluster. In silico sequence analysis revealed that 21 genes were putatively involved in amicetin biosynthesis, including 3 for regulation and transportation, 10 for disaccharide biosynthesis, and 8 for the formation of the amicetin skeleton by the linkage of cytosine, p-aminobenzoic acid (PABA), and the terminal (+)-α-methylserine moieties. The inactivation of the benzoate coenzyme A (benzoate-CoA) ligase gene amiL and the N-acetyltransferase gene amiF led to two mutants that accumulated the same two compounds, cytosamine and 4-acetamido-3-hydroxybenzoic acid. These data indicated that AmiF functioned as an amide synthethase to link cytosine and PABA. The inactivation of amiR, encoding an acyl-CoA-acyl carrier protein transacylase, resulted in the production of plicacetin and norplicacetin, indicating AmiR to be responsible for attachment of the terminal methylserine moiety to form another amide bond. These findings implicated two alternative strategies for amide bond formation in amicetin biosynthesis. PMID:22267658

Synethesis of cyclic ketal from soybean oil and fatty esters

USDA-ARS?s Scientific Manuscript database

In this work we have shown a facile and environmentally friendly reaction to form a cyclic ketal out of soybean oil, methyl soyate, methyl linoleate, and methyl oleate. There are many advantages of this reaction. First, the ketal reaction produces a branched fatty acid moiety and is reversible. S...

High-titer production and strong antimicrobial activity of sophorolipids from Rhodotorula bogoriensis

USDA-ARS?s Scientific Manuscript database

Rhodotorula bogoriensis produces sophorolipids (SLs) that contain 13-hydroxydocosanoic acid (OH-C22) as the lipid moiety. A systematic study was conducted to further understand the fermentative production of SLs containing OH-C22 (C22-SL) by R. bogoriensis. Shake-flask studies showed that R. bogor...

Controlled self-assembling structures of ferrocene-dipeptide conjugates composed of Ala-Pro-NHCH2CH2SH chain.

PubMed

Moriuchi, Toshiyuki; Nishiyama, Taiki; Tayano, Yoshiki; Hirao, Toshikazu

2017-12-01

Bioorganometallic ferrocene-dipeptide conjugates with the Ala-Pro-cysteamine chain, Fc-L-Ala-L-Pro-NHCH 2 CH 2 SH (2) and Fc-L-Ala-D-Pro-NHCH 2 CH 2 SH (4) (Fc=ferrocenoyl), were prepared by the reduction of the ferrocene-dipeptide conjugates, Fc-L-Ala-L-Pro-cystamine-L-Pro-L-Ala-Fc (1) or Fc-L-Ala-D-Pro-cystamine-D-Pro-L-Ala-Fc (3), respectively. Control of the self-assembling structures of the ferrocene-dipeptide conjugates was demonstrated by changing the chirality of the amino acid. The molecular structure of 2 composed of the L-Ala-L-Pro-NHCH 2 CH 2 SH chain confirmed the formation of intramolecular hydrogen bond of N-H⋯N pattern between the NH of cysteamine moiety and the nitrogen of Pro moiety. Furthermore, intermolecular hydrogen bonds between NH (Ala) and CO (Pro of another molecule) and between NH (cysteamine) and CO (the ferrocenoyl moiety of another molecule) were formed, wherein each molecule is connected to four neighboring molecules by continuous intermolecular hydrogen bonds to form the hydrogen-bonded molecular assembling structure. On the contrary, the left-handed helical assembly through an intermolecular hydrogen-bonding network of 15-membered intermolecularly hydrogen-bonded ring between NH (Ala) and CO (the ferrocenoyl moiety of another molecule) and between NH (the cysteamine moiety of another molecule) and CO (Ala) was observed in the crystal packing of 4 composed of the L-Ala-D-Pro-NHCH 2 CH 2 SH chain. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis of a series of chlorogenic acid isomers using differential ion mobility and tandem mass spectrometry.

PubMed

Willems, Jamie L; Khamis, Mona M; Mohammed Saeid, Waleed; Purves, Randy W; Katselis, George; Low, Nicholas H; El-Aneed, Anas

2016-08-24

Chlorogenic acids are among the most abundant phenolics found in the human diet. Of these, the mono-caffeoylquinic acids are the predominant phenolics found in fruits, such as apples and pears, and products derived from them. In this research, a comprehensive study of the electrospray ionization (ESI) tandem mass spectrometric (MS/MS) dissociation behavior of the three most common mono-caffeoylquinic acids, namely 5-O-caffeoylquinic acid (5-CQA), 3-O-caffeoylquinic acid (3-CQA) and 4-O-caffeoylquinic acid (4-CQA), were determined using both positive and negative ionization. All proposed structures of the observed product ions were confirmed with second-generation MS(3) experiments. Similarities and differences between the dissociation pathways in the positive and negative ion modes are discussed, confirming the proposed structures and the established MS/MS fingerprints. MS/MS dissociation was primarily driven via the cleavage of the ester bond linking the quinic acid moiety to the caffeic acid moiety within tested molecules. Despite being structural isomers with the same m/z values and dissociation behaviors, the MS/MS data in the negative ion mode was able to differentiate the three isomers based on ion intensity for the major product ions, observed at m/z 191, 179 and 173. This differentiation was consistent among various MS instruments. In addition, ESI coupled with high-field asymmetric waveform ion mobility spectrometry-mass spectrometry (ESI-FAIMS-MS) was employed for the separation of these compounds for the first time. By combining MS/MS data and differential ion mobility, a method for the separation and identification of mono-caffeoylquinic in apple/pear juice samples was developed with a run time of less than 1 min. It is envisaged that this methodology could be used to identify pure juices based on their chlorogenic acid profile (i.e., metabolomics), and could also be used to detect juice-to-juice adulteration (e.g., apple juice addition to pear juice). Copyright © 2016 Elsevier B.V. All rights reserved.

Support for the Delisting of Decontaminated Liquid Chemical Surety Materials as Listed Hazardous Waste from Specific Sources (STATE) MD02 in COMAR 10.51.02.16-1

DTIC Science & Technology

1988-11-01

results. On the contrary, the active decon moiety in both cases is the hydroxyl ion (0OH), and the agent being decontaminated reacts exactly the same...methods. A review of method3 utilized to determine the concentration of active material before and after the decontamination process. Included are the most...isolation of acid A, acid B will probably be excluded by the forces active in the crystallization process. Acid B will therefore be missed in the overall

The uniqueness of humic substances in each of soil, stream and marine environments

USGS Publications Warehouse

Malcolm, R.L.

1990-01-01

Definitive compositional differences are shown to exist for both fulvic acids and humic acids from soil, stream and marine environments by five different methods (1H and 13C NMR spectroscopy, 14C age and ?? 13C isotopic analyses, amino acid analyses and pyrolysis-mass spectrometry). Definitive differences are also found between fulvic acids and humic acids within each environment. These differences among humic substances from various sources are more readily discerned because the method employed for the isolation of humic substances from all environments excludes most of the non-humic components and results in more purified humic isolates from water and soils. The major compositional aspects of fulvic acids and humic acids which determine the observed characteristic differences in each environment are the amounts and compositions of saccharide, phenolic, methoxyl, aromatic, hydrocarbon, amino acid and nitrogen moieties.

Microsporols A-C from the Plant Endophytic Fungus Pestalotiopsis microspore.

PubMed

Wu, Xianfu; Wang, Yadan; Liu, Shuchun; Liu, Xinzhong; Guo, Liangdong

2015-10-01

Three new ambuic acid derivatives, microsporols A-C (1-3) and the known compound ambuic acid (4), were isolated from the solid-substrate fermentation cultures of the plant endophytic fungus Pestalotiopsis microspora. Their structures were elucidated primarily by NMR experiments. The absolute configurations of the 6,7-diol moiety in 1 and 2 were assigned using the Snatzke's method, whereas that of 3 was deduced by circular dichroism (CD) exciton chirality method. Compounds 1, 3, and 4 showed moderate 5-lipoxygenase (5-LOX) inhibitory effects.

Total synthesis of (+)-achalensolide based on the rh(i)-catalyzed allenic Pauson-Khand-type reaction.

PubMed

Hirose, Toshiyuki; Miyakoshi, Naoki; Mukai, Chisato

2008-02-01

The first total synthesis of (+)-achalensolide was achieved from a commercially available d-(-)-isoascorbic acid. The known epoxide, derived from d-(-)-isoascorbic acid, was converted into the allenyne, the Rh(I)-catalyzed Pauson-Khand-type reaction of which directly provided the bicyclo[5.3.0]decane system, a core framework of the title natural product. The construction of the gamma-lactone moiety and some chemical modifications resulted in the completion of the total synthesis of (+)-achalensolide.

Analyte interactions with a new ditopic dansylamide-nitrobenzoxadiazole dyad: a combined photophysical, NMR, and theoretical (DFT) study.

PubMed

Bhoi, Abhas Kumar; Das, Sudhir Kumar; Majhi, Debashis; Sahu, Prabhat Kumar; Nijamudheen, A; N, Anoop; Rahaman, Abdur; Sarkar, Moloy

2014-08-21

We report herein the synthesis and photophysical studies on a new multicomponent chemosensor dyad comprising two fluorescing units, dansylamide (DANS) and nitrobenzoxadiazole (NBD). The system has been developed to investigate receptor-analyte binding interactions in the presence of both cations and anions in a single molecular system. A dimethyl amino (in the DANS unit) group is used as a receptor for cations, and acidic hydrogens of sulfonamide and the NBD group are used as receptors for anions. The system is characterized by conventional analytical techniques. The photophysical properties of this supramolecular system in the absence and presence of various metal ions and nonmetal ions as additives are investigated in an acetonitrile medium. Utility of this system in an aqueous medium has also been demonstrated. The absorption and fluorescence spectrum of the molecular system consists of a broad band typical of an intramolecular charge-transfer (ICT) transition. A low quantum yield and lifetime of the NBD moiety in the present dyad indicates photoinduced electron transfer (PET) between DANS and the NBD moiety. The fluorescence intensity of the system is found to decrease in the presence of fluoride and acetate anions; however, the quenching is found to be much higher for fluoride. This quenching behavior is attributed to the enhanced PET from the anion receptor to the fluorophore moiety. The mechanistic aspect of the fluoride ion signaling behavior has also been studied by infrared (IR) and (1)H NMR experiments. The hydrogen bonding interaction between the acidic NH protons of the DPN moiety and F(-) is found to be primarily responsible for the fluoride selective signaling behavior. While investigating the cation signaling behavior, contrary to anions, significant fluorescence enhancement has been observed only in the presence of transition-metal ions. This behavior is rationalized by considering the disruption of PET communication between DANS and the NBD moiety due to transition-metal ion binding. Theoretical (density functional theory) studies are also performed for the better understanding of the receptor-analyte interaction. Interestingly, negative cooperativity in binding is observed when the interaction of this system is studied in the presence of both Zn(2+) and F(-). Fluorescence microscopy studies also revealed that the newly developed fluorescent sensor system can be employed as an imaging probe in live cells.

Hyaluronic acid-green tea catechin micellar nanocomplexes: Fail-safe cisplatin nanomedicine for the treatment of ovarian cancer without off-target toxicity.

PubMed

Bae, Ki Hyun; Tan, Susi; Yamashita, Atsushi; Ang, Wei Xia; Gao, Shu Jun; Wang, Shu; Chung, Joo Eun; Kurisawa, Motoichi

2017-12-01

The green tea catechin, (-)-epigallocatechin-3-O-gallate (EGCG), has gained significant attention as a potent adjuvant to enhance the antitumor efficacy of cisplatin while mitigating its harmful side effects. Herein we report the development of a fail-safe cisplatin nanomedicine constructed with hyaluronic acid-EGCG conjugate for ovarian cancer therapy. A simple mixing of this conjugate and cisplatin induces spontaneous self-assembly of micellar nanocomplexes having a spherical core-shell structure. The surface-exposed hyaluronic acid enables efficient delivery of cisplatin into CD44-overexpressing cancer cells via receptor-mediated endocytosis whereas the internally packed EGCG moieties offer an environment favorable for the encapsulation of cisplatin. In addition, the antioxidant effect of EGCG moieties ensures fail-safe protection against off-target organ toxicity originating from cisplatin-evoked oxidative stress. Pharmacokinetic and biodistribution studies reveal the prolonged blood circulation and preferential tumor accumulation of intravenously administered nanocomplexes. Moreover, the nanocomplexes exhibit superior antitumor efficacy over free cisplatin while displaying no toxicity in both a subcutaneous xenograft model and peritoneal metastatic model of human ovarian cancer. Our findings demonstrate proof of concept for the feasibility of green tea catechin-based micellar nanocomplexes as a safe and effective cisplatin nanomedicine for ovarian cancer treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthetic Design of Polysulfone Membranes: Morphological Effect on Property and Performance in Flow Batteries

NASA Astrophysics Data System (ADS)

Gindt, Brandon

This dissertation outlines a novel path towards improved understanding and function of proton exchange membranes (PEMs) for redox flow batteries, a large-scale battery storage device. This research uses synthetic methods and nanotechnology through two different approaches to prepare tailored polymer membranes: 1) Ion exchange membranes with enhanced chemical structures to promote membrane morphology on the nano-scale were prepared. Specifically, functional polysulfones (PSUs) were synthesized from different pre-sulfonated monomers. These PSUs have controlled placement and content of unique sulfonic acid moieties. PEMs were fabricated and characterized. The new PEMs showed desirable physical properties and performance in a vanadium redox flow battery (VRFB) cell. 2) Nanoporous PSU membranes were fabricated via post-hydrolysis of polylactide (PLA) from PLA-PSU-PLA triblock copolymer membranes. The controlled morphology and pore size of the resulting nanoporous membranes were evaluated by different microscopy and scattering techniques to understand structure-property relationships. Further, the resulting nanopore surface was chemically modified with sulfonic acid moieties. Membranes were analyzed and evaluated as separators for a VRFB. The chemically modified nanoporous PEMs exhibited unique behavior with respect to their ion conductivity when exposed to solutions of increasing acid concentration. In addition, the hierarchical micro-nanoporous membranes developed further showed promising structure and properties.

Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L (CbpL) Contributing to Pneumococcal Pathogenesis

NASA Astrophysics Data System (ADS)

Gutiérrez-Fernández, Javier; Saleh, Malek; Alcorlo, Martín; Gómez-Mejía, Alejandro; Pantoja-Uceda, David; Treviño, Miguel A.; Voß, Franziska; Abdullah, Mohammed R.; Galán-Bartual, Sergio; Seinen, Jolien; Sánchez-Murcia, Pedro A.; Gago, Federico; Bruix, Marta; Hammerschmidt, Sven; Hermoso, Juan A.

2016-12-01

The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca2+-binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp_Lipoprotein domain. Our structural and infection assays indicate an important role of the whole multimodular protein allowing both to locate CbpL at specific places on the cell wall and to interact with host components in order to facilitate pneumococcal lung infection and transmigration from nasopharynx to the lungs and blood. CbpL implication in both resistance against killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein as relevant among the pathogenic arsenal of the pneumococcus.

Effects of targeting moiety, linker, bifunctional chelator, and molecular charge on biological properties of 64Cu-labeled triphenylphosphonium cations.

PubMed

Kim, Young-Seung; Yang, Chang-Tong; Wang, Jianjun; Wang, Lijun; Li, Zi-Bo; Chen, Xiaoyuan; Liu, Shuang

2008-05-22

In this report, we present the synthesis and evaluation of six new 64Cu-labeled triphenylphosphonium (TPP) cations. Biodistribution studies were performed using the athymic nude mice bearing U87MG human glioma xenografts to explore the impact of TPP moieties, linkers, bifunctional chelators (BFCs), and molecular charge on biological properties of 64Cu radiotracers. On the basis of the results from this study, it is concluded that (1) mTPP (tris(4-methoxyphenyl)phosphonium) is a better mitochondrion-targeting molecule than TPP and 3mTPP (tris(2,4,6-trimethoxyphenyl)phosphonium); (2) DO3A (1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid) and DO2A (1,4,7,10-tetraazacyclododecane-4,7-diacetic acid) are suitable BFCs for the 64Cu-labeling of TPP cations; (3) NOTA-Bn ( S-2-(4-thioureidobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid) has a significant adverse effect on the radiotracer tumor uptake and tumor-to-background ratios; and (4) monoanionic BFCs should be avoided to ensure that 64Cu chelate has a neutral or negative charge. Considering the tumor uptake and tumor/liver ratios, 64Cu(DO2A-xy-TPP)+ is the best candidate for more extensive evaluations in different tumor-bearing animal models.

Brain delivery of proteins via their fatty acid and block copolymer modifications

PubMed Central

Yi, Xiang; Kabanov, Alexander V.

2014-01-01

It is well known that hydrophobic small molecules penetrate cell membranes better than hydrophilic molecules. Amphiphilic molecules that dissolve both in lipid and aqueous phases are best suited for membrane transport. Transport of biomacromolecules across physiological barriers, e.g. the blood-brain barrier, is greatly complicated by the unique structure and function of such barriers. Two decades ago we adopted a simple philosophy that to increase protein delivery to the brain one needs to modify this protein with hydrophobic moieties. With this general idea we began modifying proteins (antibodies, enzymes, hormones, etc.) with either hydrophobic fatty acid residues or amphiphilic block copolymer moieties, such as poy(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (pluronics or poloxamers) and more recently, poly(2-oxasolines). This simple approach has resulted in impressive successes in CNS drug delivery. We present a retrospective overview of these works initiated in the Soviet Union in 1980s, and then continued in the United States and other countries. Notably some of the early findings were later corroborated by brain pharmacokinetic data. Industrial development of several drug candidates employing these strategies has followed. Overall modification by hydrophobic fatty acids residues or amphiphilic block copolymers represents a promising and relatively safe strategy to deliver proteins to the brain. PMID:24160902

Dual Functions of the Trans-2-Enoyl-CoA Reductase TER in the Sphingosine 1-Phosphate Metabolic Pathway and in Fatty Acid Elongation*

PubMed Central

Wakashima, Takeshi; Abe, Kensuke; Kihara, Akio

2014-01-01

The sphingolipid metabolite sphingosine 1-phosphate (S1P) functions as a lipid mediator and as a key intermediate of the sole sphingolipid to glycerophospholipid metabolic pathway (S1P metabolic pathway). In this pathway, S1P is converted to palmitoyl-CoA through 4 reactions, then incorporated mainly into glycerophospholipids. Although most of the genes responsible for the S1P metabolic pathway have been identified, the gene encoding the trans-2-enoyl-CoA reductase, responsible for the saturation step (conversion of trans-2-hexadecenoyl-CoA to palmitoyl-CoA) remains unidentified. In the present study, we show that TER is the missing gene in mammals using analyses involving yeast cells, deleting the TER homolog TSC13, and TER-knockdown HeLa cells. TER is known to be involved in the production of very long-chain fatty acids (VLCFAs). A significant proportion of the saturated and monounsaturated VLCFAs are used for sphingolipid synthesis. Therefore, TER is involved in both the production of VLCFAs used in the fatty acid moiety of sphingolipids as well as in the degradation of the sphingosine moiety of sphingolipids via S1P. PMID:25049234

Synthesis of amino acid conjugates to 2-imino-3-methylene-5-carboxypyrrolidine and 2-imino-3-methylene-6-carboxypiperidine.

PubMed

Mitchell, Robin E

2010-03-15

The four stereomers of 2-imino-3-methylene-5-L(carboxy-L-valyl)pyrrolidine, a bacterial metabolite that is inhibitory to the fire blight bacterium Erwinia amylovora, were synthesised and compared for antibacterial activity. Several alternative amino acid conjugates with L,L-stereochemistry were also prepared, and the synthesis was extended to 3-methylenepiperidine-6-L-carboxylic acid and a selection of 2-imino-3-methylenepiperidine-6-L-carboxy-L-amino acid conjugates. All synthetic amino acid conjugates (L,L-stereomers) were inhibitory to the growth of E. amylovora. The likely participation of the conjugated iminomethylene moiety as a Michael acceptor is implicated. Copyright 2010 Elsevier Ltd. All rights reserved.

Separator for alkaline batteries and method of making same

NASA Technical Reports Server (NTRS)

Hoyt, H. E.; Pfluger, H. L. (Inventor)

1970-01-01

The preparation of membranes suitable for use as separators in concentrated alkaline battery cells by selective solvolysis of copolymers of methacrylate esters with acrylate esters followed by addition of a base and to the resultant products is described. The method of making copolymers by first copolymerizing a methacrylate ester (or esters) with a more readily hydrolyzable ester, followed by a selective saponification whereby the methacrylate ester moieties remain essentially intact and the readily hydrolyzable ester moiety is suponified and to the partial or complete neutralization of the relatively brittle copolymer acid with a base to make membranes which are sufficiently flexible in the dry state so that they may be wrapped around electrodes without damage by handling is described.

Understanding Organic Film Behavior on Alloy and Metal Oxides

PubMed Central

Raman, Aparna; Quiñones, Rosalynn; Barriger, Lisa; Eastman, Rachel; Parsi, Arash

2010-01-01

Native oxide surfaces of stainless steel 316L and Nitinol alloys and their constituent metal oxides namely, nickel, chromium, molybdenum, manganese, iron and titanium were modified with long chain organic acids to better understand organic film formation. The adhesion and stability of films of octadecylphosphonic acid, octadecylhydroxamic acid, octadecylcarboxylic acid and octadecylsulfonic acid on these substrates was examined in this study. The films formed on these surfaces were analyzed by diffuse reflectance infrared Fourier transform spectroscopy, contact angle goniometry, atomic force microscopy and matrix assisted laser desorption ionization mass spectrometry. The effect of the acidity of the organic moiety and substrate composition on the film characteristics and stability is discussed. Interestingly, on the alloy surfaces, the presence of less reactive metal sites does not inhibit film formation. PMID:20039608

Antibody binding of circulating ergot alkaloids in cattle grazing tall fescue.

PubMed

Hill, N S; Thompson, F N; Dawe, D L; Stuedemann, J A

1994-03-01

Direct evidence linking alkaloids found in endophyte-infected tall fescue forage with the livestock disorder known as fescue toxicosis is lacking. Physiologic effects of fescue toxicosis include reduced serum prolactin concentration in cattle. A monoclonal antibody specific to the lysergic moiety of ergot alkaloids was developed in mice after creating an immunogen by linking lysergol to human serum albumin. The antibody was specific to the lysergic moiety and, therefore, it cross-reacted with ergot alkaloids, lysergic acid, and lysergol. The antibody did not cross-react with alkaloid derivatives that had bromated or hydrogenated lysergic ring moieties. Fescue toxicosis conditions were elicited in yearling Angus steers by permitting them to graze endophyte-infected tall fescue containing > 650 micrograms/kg of ergovaline for 60 days. Passive immunization of steers by infusion of the monoclonal antibody increased serum prolactin concentration by 7 ng/ml, beginning immediately after infusion. Control steers did not respond to treatment with bovine serum albumin. Active immunization of yearling Angus heifers with immunogens containing lysergol or ergonovine linked to human serum albumin resulted in an antibody response.

Ubiquitin--conserved protein or selfish gene?

PubMed

Catic, André; Ploegh, Hidde L

2005-11-01

The posttranslational modifier ubiquitin is encoded by a multigene family containing three primary members, which yield the precursor protein polyubiquitin and two ubiquitin moieties, Ub(L40) and Ub(S27), that are fused to the ribosomal proteins L40 and S27, respectively. The gene encoding polyubiquitin is highly conserved and, until now, those encoding Ub(L40) and Ub(S27) have been generally considered to be equally invariant. The evolution of the ribosomal ubiquitin moieties is, however, proving to be more dynamic. It seems that the genes encoding Ub(L40) and Ub(S27) are actively maintained by homologous recombination with the invariant polyubiquitin locus. Failure to recombine leads to deterioration of the sequence of the ribosomal ubiquitin moieties in several phyla, although this deterioration is evidently constrained by the structural requirements of the ubiquitin fold. Only a few amino acids in ubiquitin are vital for its function, and we propose that conservation of all three ubiquitin genes is driven not only by functional properties of the ubiquitin protein, but also by the propensity of the polyubiquitin locus to act as a 'selfish gene'.

Fluorescent film sensors based on SAMs of pyrene derivatives for detecting nitroaromatics in aqueous solutions

NASA Astrophysics Data System (ADS)

Zhang, Shujuan; Ding, Liping; Lü, Fengting; Liu, Taihong; Fang, Yu

2012-11-01

The detection of nitroaromatics in aqueous solutions by a novel pyrene-functionalized film has been investigated in the present study. The pyrene moieties were attached on the glass surface via a long flexible spacer based on self-assembled monolayer technique. Steady-state fluorescence measurements revealed that these surface-attached pyrene moieties exhibited both monomer and excimer emission. Nitroaromatics such as 2,4,6-trinitrotoluene, 2,4-dinitrotoluene, and 2,4,6-trinitrophenol (picric acid) were found to efficiently quench the fluorescence emission of this film. The quenching results demonstrated that the excimer emission of these surface-confined pyrene moieties is more sensitive to the presence of nitroaromatics than the monomer emission. The quenching mechanism was examined through fluorescence lifetime measurement and it revealed that the quenching is static in nature and may be caused by electron transfer from the polycyclic aromatics to the nitroaromatics. Furthermore, the response of the film to nitroaromatics is fast and reversible, and the obtained film shows promising potentials in detecting explosives in aqueous environment.

A study on the interactions of amino acids with nitrogen doped graphene; docking, MD simulation, and QM/MM studies.

PubMed

Ghadari, Rahim

2016-02-14

The binding properties of twenty amino acids with nitrogen-doped graphene structures were studied using docking, MD simulation, and QM/MM methods. TDDFT studies were carried out to investigate the change in the electronic properties of the amino acids because of the presence of the solvent and nitrogen-doped graphene. The results revealed that π-π interactions between the amino acids with a benzene moiety and the surface of the graphene are the most important interactions. The observed red shifts in the TDDFT results which were related to the lower LUMO energies and higher HOMO energies are consistent with this statement.

Three new fatty acid esters from the mushroom Boletus pseudocalopus.

PubMed

Kim, Ki Hyun; Choi, Sang Un; Lee, Kang Ro

2012-06-01

A bioassay-guided fractionation and chemical investigation of a MeOH extract of the Korean wild mushroom Boletus pseudocalopus resulted in the identification of three new fatty acid esters, named calopusins A-C (1-3), along with two known fatty acid methyl esters (4-5). These new compounds are structurally unique fatty acid esters with a 2,3-butanediol moiety. Their structures were elucidated through 1D- and 2D-NMR spectroscopic data and GC-MS analysis as well as a modified Mosher's method. The new compounds 1-3 showed significant inhibitory activity against the proliferation of the tested cancer cell lines with IC(50) values in the range 2.77-12.51 μM.

The Nitrogen Moieties of Dietary Nonessential Amino Acids Are Distinctively Metabolized in the Gut and Distributed to the Circulation in Rats.

PubMed

Nakamura, Hidehiro; Kawamata, Yasuko; Kuwahara, Tomomi; Sakai, Ryosei

2017-08-01

Background: Although previous growth studies in rodents have indicated the importance of dietary nonessential amino acids (NEAAs) as nitrogen sources, individual NEAAs have different growth-promoting activities. This phenomenon might be attributable to differences in the nitrogen metabolism of individual NEAAs. Objective: The aim of this study was to compare nitrogen metabolism across dietary NEAAs with the use of their 15 N isotopologues. Methods: Male Fischer rats (8 wk old) were given 1.0 g amino acid-defined diets containing either 15 N-labeled glutamate, glutamine (amino or amide), aspartate, alanine, proline, glycine, or serine hourly for 5-6 h. Then, steady-state amino acid concentrations and their 15 N enrichments in the gut and in portal and arterial plasma were measured by an amino acid analyzer and LC tandem mass spectrometry, respectively. Results: The intestinal 15 N distribution and portal-arterial balance of 15 N metabolites indicated that most dietary glutamate nitrogen (>90% of dietary input) was incorporated into various amino acids, including alanine, proline, and citrulline, in the gut. Dietary aspartate nitrogen, alanine nitrogen, and amino nitrogen of glutamine were distributed similarly to other amino acids both in the gut and in the circulation. In contrast, incorporation of the nitrogen moieties of dietary proline, serine, and glycine into other amino acids was less than that of other NEAAs, although interconversion between serine and glycine was very active. Cluster analysis of 15 N enrichment data also indicated that dietary glutamate nitrogen, aspartate nitrogen, alanine nitrogen, and the amino nitrogen of glutamine were distributed similarly to intestinal and circulating amino acids. Further, the analysis revealed close relations between intestinal and arterial 15 N enrichment for each amino acid. The steady-state 15 N enrichment of arterial amino acids indicated that substantial amounts of circulating amino acid nitrogen are derived from dietary NEAAs. Conclusions: The present results revealed similarities and differences among NEAAs in terms of their intestinal nitrogen metabolism in rats and indicated substantial entry of dietary NEAA nitrogen into circulating amino acid nitrogen, presumably primarily through metabolism in the gut. © 2017 American Society for Nutrition.

Green leaf volatiles and oxygenated metabolite emission bursts from mesquite branches following light-dark transitions.

PubMed

Jardine, K; Barron-Gafford, G A; Norman, J P; Abrell, L; Monson, R K; Meyers, K T; Pavao-Zuckerman, M; Dontsova, K; Kleist, E; Werner, C; Huxman, T E

2012-09-01

Green leaf volatiles (GLVs) are a diverse group of fatty acid-derived compounds emitted by all plants and are involved in a wide variety of developmental and stress-related biological functions. Recently, GLV emission bursts from leaves were reported following light-dark transitions and hypothesized to be related to the stress response while acetaldehyde bursts were hypothesized to be due to the 'pyruvate overflow' mechanism. In this study, branch emissions of GLVs and a group of oxygenated metabolites (acetaldehyde, ethanol, acetic acid, and acetone) derived from the pyruvate dehydrogenase (PDH) bypass pathway were quantified from mesquite plants following light-dark transitions using a coupled GC-MS, PTR-MS, and photosynthesis system. Within the first minute after darkening following a light period, large emission bursts of both C(5) and C(6) GLVs dominated by (Z)-3-hexen-1-yl acetate together with the PDH bypass metabolites are reported for the first time. We found that branches exposed to CO(2)-free air lacked significant GLV and PDH bypass bursts while O(2)-free atmospheres eliminated the GLV burst but stimulated the PDH bypass burst. A positive relationship was observed between photosynthetic activity prior to darkening and the magnitude of the GLV and PDH bursts. Photosynthesis under (13)CO(2) resulted in bursts with extensive labeling of acetaldehyde, ethanol, and the acetate but not the C(6)-alcohol moiety of (Z)-3-hexen-1-yl acetate. Our observations are consistent with (1) the "pyruvate overflow" mechanism with a fast turnover time (<1 h) as part of the PDH bypass pathway, which may contribute to the acetyl-CoA used for the acetate moiety of (Z)-3-hexen-1-yl acetate, and (2) a pool of fatty acids with a slow turnover time (>3 h) responsible for the C(6) alcohol moiety of (Z)-3-hexen-1-yl acetate via the 13-lipoxygenase pathway. We conclude that our non-invasive method may provide a new valuable in vivo tool for studies of acetyl-CoA and fatty acid metabolism in plants at a variety of spatial scales.

Metabolite profiling of bendamustine in urine of cancer patients after administration of [14C]bendamustine.

PubMed

Dubbelman, Anne-Charlotte; Jansen, Robert S; Rosing, Hilde; Darwish, Mona; Hellriegel, Edward; Robertson, Philmore; Schellens, Jan H M; Beijnen, Jos H

2012-07-01

Bendamustine is an alkylating agent consisting of a mechlorethamine derivative, a benzimidazole group, and a butyric acid substituent. A human mass balance study showed that bendamustine is extensively metabolized and subsequently excreted in urine. However, limited information is available on the metabolite profile of bendamustine in human urine. The objective of this study was to elucidate the metabolic pathways of bendamustine in humans by identification of its metabolites excreted in urine. Human urine samples were collected up to 168 h after an intravenous infusion of 120 mg/m(2) (80-95 μCi) [(14)C]bendamustine. Metabolites of [(14)C]bendamustine were identified using liquid chromatography (high-resolution)-tandem mass spectrometry with off-line radioactivity detection. Bendamustine and a total of 25 bendamustine-related compounds were detected. Observed metabolic conversions at the benzimidazole and butyric acid moiety were N-demethylation and γ-hydroxylation. In addition, various other combinations of these conversions with modifications at the mechlorethamine moiety were observed, including hydrolysis (the primary metabolic pathway), cysteine conjugation, and subsequent biotransformation to mercapturic acid and thiol derivatives, N-dealkylation, oxidation, and conjugation with phosphate, creatinine, and uric acid. Bendamustine-derived products containing phosphate, creatinine, and uric acid conjugates were also detected in control urine incubated with bendamustine. Metabolites that were excreted up to 168 h after the infusion included products of dihydrolysis and cysteine conjugation of bendamustine and γ-hydroxybendamustine. The range of metabolic reactions is generally consistent with those reported for rat urine and bile, suggesting that the overall processes involved in metabolic elimination are qualitatively the same in rats and humans.

4-Mercaptophenylboronic acid SAMs on gold: comparison with SAMs derived from thiophenol, 4-mercaptophenol, and 4-mercaptobenzoic acid.

PubMed

Barriet, David; Yam, Chi Ming; Shmakova, Olga E; Jamison, Andrew C; Lee, T Randall

2007-08-14

We report the formation and characterization of self-assembled monolayers (SAMs) derived from the adsorption of 4-mercaptophenylboronic acid (MPBA) on gold. For comparison, SAMs derived from the adsorption of thiophenol (TP), 4-mercaptophenol (MP), and 4-mercaptobenzoic acid (MBA) were also examined. The structure and properties of the SAMs were evaluated by ellipsometry, contact-angle goniometry, polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), and X-ray photoelectron spectroscopy (XPS). Specifically, ellipsometry was used to assess the formation of monolayer films, and contact angle measurements were used to determine the surface hydrophilicity and homogeneity. Separately, PM-IRRAS was used to evaluate the molecular composition and orientation as well as the intermolecular hydrogen bonding within the SAMs. Finally, XPS was used to evaluate the film composition and surface coverage (i.e., packing density), which was observed to increase in the following order: TP < MP < MPBA < MBA. A rationalization for the observed packing differences is presented. The XPS data indicate further that ultrahigh vacuum conditions induce the partial dehydration of MPBA SAMs with the concomitant formation of surface boronic anhydride species. Overall, the analytical data collectively show that the MPBA moieties in the SAMs exist in the acid form rather than the anhydride form under ambient laboratory conditions. Furthermore, stability studies find that MPBA SAMs are surprisingly labile in basic solution, where the terminal B-C bonds are cleaved by the attack of hydroxide ion and strongly basic amine nucleophiles. The unanticipated lability observed here should be considered by those wishing to use MPBA moieties in carbohydrate-sensing applications.

Structure-mutagenicity relationship of kaurenoic acid from Xylopia sericeae (Annonaceae).

PubMed

Cavalcanti, B C; Ferreira, J R O; Moura, D J; Rosa, R M; Furtado, G V; Burbano, R R; Silveira, E R; Lima, M A S; Camara, C A G; Saffi, J; Henriques, J A P; Rao, V S N; Costa-Lotufo, L V; Moraes, M O; Pessoa, C

2010-08-30

Kaurane diterpenes are considered important compounds in the development of new highly effective anticancer chemotherapeutic agents. Genotoxic effects of anticancer drugs in non-tumour cells are of special significance due to the possibility that they induce secondary tumours in cancer patients. In this context, we evaluated the genotoxic and mutagenic potential of the natural diterpenoid kaurenoic acid (KA), i.e. (-)-kaur-16-en-19-oic acid, isolated from Xylopia sericeae St. Hill, using several standard in vitro and in vivo protocols (comet, chromosomal aberration, micronucleus and Saccharomyces cerevisiae assays). Also, an analysis of structure-activity relationships was performed with two natural diterpenoid compounds, 14-hydroxy-kaurane (1) and xylopic acid (2), isolated from X. sericeae, and three semi-synthetic derivatives of KA (3-5). In addition, considering the importance of the exocyclic double bond (C16) moiety as an active pharmacophore of KA cytotoxicity, we also evaluated the hydrogenated derivative of KA, (-)-kauran-19-oic acid (KAH), to determine the role of the exocyclic bond (C16) in the genotoxic activity of KA. In summary, the present study shows that KA is genotoxic and mutagenic in human peripheral blood leukocytes (PBLs), yeast (S. cerevisiae) and mice (bone marrow, liver and kidney) probably due to the generation of DNA double-strand breaks (DSB) and/or inhibition of topoisomerase I. Unlike KA, compounds 1-5 and KAH are completely devoid of genotoxic and mutagenic effects under the experimental conditions used in this study, suggesting that the exocyclic double bond (C16) moiety may be the active pharmacophore of the genetic toxicity of KA. 2010 Elsevier B.V. All rights reserved.

Studying the Chemistry of Cationized Triacylglycerols Using Electrospray Ionization Mass Spectrometry and Density Functional Theory Computations

NASA Astrophysics Data System (ADS)

Grossert, J. Stuart; Herrera, Lisandra Cubero; Ramaley, Louis; Melanson, Jeremy E.

2014-08-01

Analysis of triacylglycerols (TAGs), found as complex mixtures in living organisms, is typically accomplished using liquid chromatography, often coupled to mass spectrometry. TAGs, weak bases not protonated using electrospray ionization, are usually ionized by adduct formation with a cation, including those present in the solvent (e.g., Na+). There are relatively few reports on the binding of TAGs with cations or on the mechanisms by which cationized TAGs fragment. This work examines binding efficiencies, determined by mass spectrometry and computations, for the complexation of TAGs to a range of cations (Na+, Li+, K+, Ag+, NH4 +). While most cations bind to oxygen, Ag+ binding to unsaturation in the acid side chains is significant. The importance of dimer formation, [2TAG + M]+ was demonstrated using several different types of mass spectrometers. From breakdown curves, it became apparent that two or three acid side chains must be attached to glycerol for strong cationization. Possible mechanisms for fragmentation of lithiated TAGs were modeled by computations on tripropionylglycerol. Viable pathways were found for losses of neutral acids and lithium salts of acids from different positions on the glycerol moiety. Novel lactone structures were proposed for the loss of a neutral acid from one position of the glycerol moiety. These were studied further using triple-stage mass spectrometry (MS3). These lactones can account for all the major product ions in the MS3 spectra in both this work and the literature, which should allow for new insights into the challenging analytical methods needed for naturally occurring TAGs.

Purification of 2-monoacylglycerols using liquid CO2 extraction

USDA-ARS?s Scientific Manuscript database

The fatty acid moiety of 2-monoacyl-sn-glycerol (2-MAG) undergoes spontaneous acyl migration to the sn-1(3) position, resulting in a thermodynamic equilibrium of approximately 1:9 of 2-MAG to 1-monoacyl-sn-glycerol (1-MAG). Spontaneous acyl migration is an impediment to synthesizing and isolating s...

Spectrophotometric determination of reaction rates and kinetic parameters of a BAHD acyltransferase using DTNB (5,5'-dithio-bis-[2-nitrobenzoic acid])

USDA-ARS?s Scientific Manuscript database

Hydroxycinnamoyl-Coenzyme A (CoA) hydroxycinnamoyl transferases are BAHD family acyltransferases that transfer hydroxycinnamoyl moieties from a CoA-thioester to an acceptor amine or alcohol to form an N-hydroxycinnamoyl amide or O-hydroxycinnamoyl ester, respectively, with the concomitant release of...

Yakushinamides, Polyoxygenated Fatty Acid Amides That Inhibit HDACs and SIRTs, from the Marine Sponge Theonella swinhoei.

PubMed

Takada, Kentaro; Imae, Yasufumi; Ise, Yuji; Ohtsuka, Susumu; Ito, Akihiro; Okada, Shigeru; Yoshida, Minoru; Matsunaga, Shigeki

2016-09-23

Yakushinamides A (1) and B (2), prolyl amides of polyoxygenated fatty acids, have been isolated from the marine sponge Theonella swinhoei as inhibitors of HDACs and SIRTs. Their planar structures were determined by interpretation of the NMR data of the intact molecules and tandem FABMS data of the methanolysis products. For the assignment of the relative configurations of the three contiguous oxymethine carbons in 1 and 2, Kishi's universal NMR database was applied to the methanolysis products. During the assignments of relative configurations of the isolated 1-hydroxy-3-methyl moiety in 1 and the isolated 1-hydroxy-2-methyl moiety in 2, we found diagnostic NMR features to distinguish each pair of diastereomers. The absolute configurations of 1 and 2 were determined by a combination of the modified Mosher's method and Marfey's method. Although the modified Mosher's method was successfully applied to the methanolysis product of 1, this method gave an ambiguous result at C-20 when applied to the methanolysis product of 2, even after oxidative cleavage of the C-14 and C-15 bond.

Discovery of antitumor ursolic acid long-chain diamine derivatives as potent inhibitors of NF-κB.

PubMed

Jiang, Wei; Huang, Ri-Zhen; Zhang, Jing; Guo, Tong; Zhang, Meng-Ting; Huang, Xiao-Chao; Zhang, Bin; Liao, Zhi-Xin; Sun, Jing; Wang, Heng-Shan

2018-05-08

A series of inhibitors of NF-κB based on ursolic acid (UA) derivatives containing long-chain diamine moieties were designed and synthesized as well as evaluated the antitumor effects. These compounds exhibited significant inhibitory activity to the NF-κB with IC 50 values at micromolar concentrations in A549 lung cancer cell line. Among them, compound 8c exerted potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC 50 values ranged from 5.22 to 8.95 μM. Moreover, compound 8c successfully suppressed the migration of A549 cells. Related mechanism study indicated compound 8c caused cell cycle arrest at G1 phase and triggered apoptosis in A549 cells through blockage of NF-κB signalling pathway. Molecular docking study revealed that key interactions between 8c and the active site of NF-κB in which the bulky and strongly electrophilic group of long-chain diamine moieties were important for improving activity. Copyright © 2018 Elsevier Inc. All rights reserved.

Rapid Synthesis of Thiophene-Based, Organic Dyes for Dye-Sensitized Solar Cells (DSSCs) by a One-Pot, Four-Component Coupling Approach.

PubMed

Matsumura, Keisuke; Yoshizaki, Soichi; Maitani, Masato M; Wada, Yuji; Ogomi, Yuhei; Hayase, Shuzi; Kaiho, Tatsuo; Fuse, Shinichiro; Tanaka, Hiroshi; Takahashi, Takashi

2015-06-26

This one-pot, four-component coupling approach (Suzuki-Miyaura coupling/C-H direct arylation/Knoevenagel condensation) was developed for the rapid synthesis of thiophene-based organic dyes for dye-sensitized solar cells (DSSCs). Seven thiophene-based, organic dyes of various donor structures with/without the use of a 3,4-ethylenedioxythiophene (EDOT) moiety were successfully synthesized in good yields based on a readily available thiophene boronic acid pinacol ester scaffold (one-pot, 3-step, 35-61%). Evaluation of the photovoltaic properties of the solar cells that were prepared using the synthesized dyes revealed that the introduction of an EDOT structure beside a cyanoacrylic acid moiety improved the short-circuit current (Jsc) while decreasing the fill factor (FF). The donor structure significantly influenced the open-circuit voltage (Voc), the FF, and the power conversion efficiency (PCE). The use of a n-hexyloxyphenyl amine donor, and our originally developed, rigid, and nonplanar donor, both promoted good cell performance (η=5.2-5.6%). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Central-to-axial chirality transfer revealed by liquid crystals: a combined experimental and computational approach for the determination of absolute configuration of carboxylic acids with an α chirality centre.

PubMed

Ferrarini, Alberta; Ferroni, Fiammetta; Pieraccini, Silvia; Rosini, Carlo; Superchi, Stefano; Spada, Gian Piero

2011-10-01

The conversion into 6,7-dihydro-5H-dibenz[c,e]azepine (DAZ) N-protected amides is a viable route for the determination of the absolute configuration of chiral 2-substituted carboxylic acids. The biphenyl moiety of DAZ, besides being a probe of chirality for the electronic circular dichroism (ECD) spectroscopy, makes these systems suitable for configuration assignment by exploiting the chirality amplification which occurs in nematic liquid crystals. To assess the reliability of the liquid crystal method in detecting the absolute stereochemistry of chiral amides bound to a biphenyl group, we measured the helical twisting power of a series of DAZ-N-protected amides and compared these data with the results obtained from ECD measurements. We will show that the liquid crystal method, corroborated by HTP predictions, is trustworthy with our biphenyl derivatives, even when ECD spectra are ambiguous for the presence of aryl moieties displaying strong UV absorptions in the same range of the biphenyl chromophore. © 2011 Wiley-Liss, Inc.

Synthesis, characterization and electrochemical properties of 5-aza[5]helicene-CH2O-CO-MWCNTs nanocomposite

NASA Astrophysics Data System (ADS)

Fontana, F.; Melone, F.; Iannazzo, D.; Leonardi, S. G.; Neri, G.

2017-03-01

In this study, we report the preparation of a novel nanocomposite, 5-aza[5]helicene-CH2O-CO-MWCNTs, obtained by grafting the 5-aza[5]helicene moiety on the surface of multi-walled carbon nanotubes (MWCNTs). Thermogravimetry (TGA), Fourier transform-infrared spectroscopy (FTIR), ultraviolet (UV), and photoluminescence (PL) measurements provided evidence that the organic moiety is covalently grafted to the MWCNTs. The 5-aza[5]helicene-CH2O-CO-MWCNTs nanocomposite was utilized to fabricate modified commercial screen-printed carbon electrodes. Its electrochemical behavior was studied in neutral buffer solution in the presence of ferricyanide and hydroquinone (HQ). Finally, the electrochemical sensing of epinephrine in the presence of ascorbic acid by using the linear sweep voltammetry (LSV) technique was investigated. Results have demonstrated the enhanced electrocatalytic activity and excellent ability of the 5-aza[5]helicene-CH2O-CO-MWCNTs-modified electrode in the separation between the anodic peaks of epinephrine (EP) and ascorbic acid (AA), even in the presence of a high amount of AA, with a detection limit (S/N = 3) of 5 μmol l-1.

Diastereomers of lithospermic acid and lithospermic acid B from Monarda fistulosa and Lithospermum erythrorhizon.

PubMed

Murata, Toshihiro; Oyama, Kanae; Fujiyama, Minami; Oobayashi, Bunmei; Umehara, Kaoru; Miyase, Toshio; Yoshizaki, Fumihiko

2013-12-01

Monardic acids A (1) and B (2), which are (7R,8R) diastereomers of lithospermic acid (LA) and lithospermic acid B, respectively, were isolated from Monarda fistulosa. A (7S,8R) isomer (3) of LA was also isolated from this plant, and a (7R,8S) isomer (7) of LA was obtained from Lithospermum erythrorhizon. The absolute configuration of 1 was confirmed by analysis of its hydrolysates, 7-epiblechnic acid and 2R-3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid. The configuration in the dihydrobenzofuran moieties of 2, 3, and 7 was extrapolated by using the phenylglycine methyl ester method and a Cotton effect at approximately 250-260 nm in their electronic circular dichroism spectra. Diastereomers (1-3 and 7) displayed moderate hyaluronidase inhibitory and histamine release inhibitory activities. © 2013.

A Modified P1 Moiety Enhances in vitro Antiviral Activity against Various Multi-Drug-Resistant HIV-1 Variants and in vitro CNS Penetration Properties of a Novel Nonpeptidic Protease Inhibitor, GRL-10413

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amano, Masayuki; Salcedo-Gómez, Pedro Miguel; Zhao, Rui

We here report that GRL-10413, a novel non-peptidic HIV-1 protease inhibitor (PI) containing a modified P1 moiety and a sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (EC 50: 0.00035 - 0.0018 μM) with minimal cytotoxicity (CC 50: 35.7 μM). GRL-10413 blocked the infectivity and replication of HIV-1 NL4-3variants selected by up to 5 μM concentrations of atazanavir, lopinavir, or amprenavir (EC 50: 0.0021 - 0.0023 μM). GRL-10413 also maintained its strong antiviral activity against multi-drug-resistant clinical HIV-1 variants isolated from patients, who no longer responded to various antiviral regimens after long-term antiretroviral therapy. Themore » development of resistance against GRL-10413 was significantly delayed compared to that of APV. In addition, GRL-10413 showed a favorable central nervous system (CNS) penetration property as assessed with anin vitroblood brain barrier (BBB) reconstruction system. Analysis of the crystal structure of HIV-1 protease in complex with GRL-10413 demonstrated that the modified P1 moiety of GRL-10413 has a greater hydrophobic surface area and makes greater van der Waals contacts with active-site amino acids of protease than in the case of darunavir. Moreover, the chlorine substituent in the P1 moiety interacts with protease in two distinct configurations. The present data demonstrate that GRL-10413 has desirable features for treating patients infected with wild-type and/or multi-drug-resistant HIV-1 variants with favorable CNS-penetration capability and that the newly modified P1-moiety may confer desirable features in designing novel anti-HIV-1 PIs.« less

Antigenic determinants of Staphylococcus aureus type 5 and type 8 capsular polysaccharide vaccines.

PubMed

Fattom, A I; Sarwar, J; Basham, L; Ennifar, S; Naso, R

1998-10-01

Bacterial capsular polysaccharides (CP) are carbohydrate polymers comprised of repeating saccharide units. Several of these CP have side chains attached to their backbone structures. The side chains may include O-acetyl, phosphate, sialic acid, and other moieties. Those moieties represent the immunodominant epitopes and the most functional ones. The clinically significant Staphylococcus aureus type 5 CP (CP 5) and type 8 CP (CP 8) are comprised of a trisaccharide repeat unit with one O-acetyl group attached to each repeat unit. The immunogenicity of these CP and the functionality of antibodies to the backbone and the O-acetyl moieties were investigated. Immunization with the native CP conjugates (CP with 75% O-acetylation) elicited a high proportion of antibodies directed against the O-acetyl moiety. Nonetheless, all of the vaccinees produced antibodies to the backbone moieties as well. Conjugate vaccines made of de-O-acetylated CP elicited backbone antibodies only. Antibodies to both backbone and O-acetyl groups were found to be opsonic against S. aureus strains which varied in their O-acetyl content. Absorption studies with O-acetylated and de-O-acetylated CP showed that (i) native CP conjugates generated antibodies to both backbone and O-acetyl groups and (ii) O-acetylated isolates were opsonized by both populations of antibodies while the non-O-acetylated strains were predominantly opsonized by the backbone antibodies. These results suggest that S. aureus CP conjugate vaccines elicit multiple populations of antibodies with diverse specificities. Moreover, the antibodies of different specificities (backbone or O-acetyl) are all functional and efficient against the variations in bacterial CP that may occur among clinically significant S. aureus pathogenic isolates.

Analysis of the constituents in jojoba wax used as a food additive by LC/MS/MS.

PubMed

Tada, Atsuko; Jin, Zhe-Long; Sugimoto, Naoki; Sato, Kyoko; Yamazaki, Takeshi; Tanamoto, Kenichi

2005-10-01

Jojoba wax is a natural gum base used as a food additive in Japan, and is obtained from jojoba oil with a characteristically high melting point. Although the constituents of jojoba oil have been reported, the quality of jojoba wax used as a food additive has not yet been clarified. In order to evaluate its quality as a food additive and to obtain basic information useful for setting official standards, we investigated the constituents and their concentrations in jojoba wax. LC/MS analysis of the jojoba wax showed six peaks with [M+H]+ ions in the range from m/z 533.6 to 673.7 at intervals of m/z 28. After isolation of the components of the four main peaks by preparative LC/MS, the fatty acid and long chain alcohol moieties of the wax esters were analyzed by methanolysis and hydrolysis, followed by GC/MS. The results indicated that the main constituents in jojoba wax were various kinds of wax esters, namely eicosenyl octadecenoate (C20:1-C18:1) (1), eicosenyl eicosenoate (C20:1-C20:1) (II), docosenyl eicosenoate (C22:1-C20:1) (III), eicosenyl docosenoate (C20:1-C22:1) (IV) and tetracosenyl eiosenoate (C24:1-C20:1) (V). To confirm and quantify the wax esters in jojoba wax directly, LC/MS/MS analysis was performed. The product ions corresponding to the fatty acid moieties of the wax esters were observed, and by using the product ions derived from the protonated molecular ions of wax esters the fatty acid moieties were identified by MRM analysis. The concentrations of the wax esters I, II and III, in jojoba wax were 5.5, 21.4 and 37.8%, respectively. In summary, we clarified the main constituents of jojoba wax and quantified the molecular species of the wax esters without hydrolysis by monitoring their product ions, using a LC/MS/MS system.

Nanofibers formed through pi...pi stacking of the complexes of glucosyl-C2-salicyl-imine and phenylalanine: characterization by microscopy, modeling by molecular mechanics, and interaction by alpha-helical and beta-sheet proteins.

PubMed

Acharya, Amitabha; Ramanujam, Balaji; Mitra, Atanu; Rao, Chebrolu P

2010-07-27

This paper deals with the self-assembly of the 1:1 complex of two different amphiphiles, namely, a glucosyl-salicyl-imino conjugate (L) and phenylalanine (Phe), forming nanofibers over a period of time through pi...pi interactions. Significant enhancement observed in the fluorescence intensity of L at approximately 423 nm band and the significant decrease observed in the absorbance of the approximately 215 nm band are some characteristics of this self-assembly. Matrix-assisted laser desorption ionization/time of flight titration carried out at different time intervals supports the formation of higher aggregates. Atomic force microscopy (AFM), transmission electron microscopy, and scanning electron miscroscopy results showed the formation of nanofibers for the solutions of L with phenylalanine. In dynamic light scattering measurements, the distribution of the particles extends to a higher diameter range over time, indicating a slow kinetic process of assembly. Similar spectral and microscopy studies carried out with the control molecules support the role of the amino acid moiety over the simple -COOH moiety as well as the side chain phenyl moiety in association with the amino acid, in the formation of these fibers. All these observations support the presence of pi...pi interactions between the initially formed 1:1 complexes leading to the fiber formation. The aggregation of 1:1 complexes leading to fibers followed by the formation of bundles has been modeled by molecular mechanics studies. Thus the fiber formation with L is limited to phenylalanine and not to any other naturally occurring amino acid and hence a polymer composed of two different biocompatible amphiphiles. AFM studies carried out between the fiber forming mixture and proteins resulted in the observation that only BSA selectively adheres to the fiber among the three alpha-helical and two beta-sheet proteins studied and hence may be of use in some medical applications.

Arginine mimetic structures in biologically active antagonists and inhibitors.

PubMed

Masic, Lucija Peterlin

2006-01-01

Peptidomimetics have found wide application as bioavailable, biostable, and potent mimetics of naturally occurring biologically active peptides. L-Arginine is a guanidino group-containing basic amino acid, which is positively charged at neutral pH and is involved in many important physiological and pathophysiological processes. Many enzymes display a preference for the arginine residue that is found in many natural substrates and in synthetic inhibitors of many trypsin-like serine proteases, e.g. thrombin, factor Xa, factor VIIa, trypsin, and in integrin receptor antagonists, used to treat many blood-coagulation disorders. Nitric oxide (NO), which is produced by oxidation of L-arginine in an NADPH- and O(2)-dependent process catalyzed by isoforms of nitric oxide synthase (NOS), exhibits diverse roles in both normal and pathological physiologies and has been postulated to be a contributor to the etiology of various diseases. Development of NOS inhibitors as well as analogs and mimetics of the natural substrate L-arginine, is desirable for potential therapeutic use and for a better understanding of their conformation when bound in the arginine binding site. The guanidino residue of arginine in many substrates, inhibitors, and antagonists forms strong ionic interactions with the carboxylate of an aspartic acid moiety, which provides specificity for the basic amino acid residue in the active side. However, a highly basic guanidino moiety incorporated in enzyme inhibitors or receptor antagonists is often associated with low selectivity and poor bioavailability after peroral application. Thus, significant effort is focused on the design and preparation of arginine mimetics that can confer selective inhibition for specific trypsin-like serine proteases and NOS inhibitors as well as integrin receptor antagonists and possess reduced basicity for enhanced oral bioavailability. This review will describe the survey of arginine mimetics designed to mimic the function of the arginine moiety in numerous peptidomimetic compounds (thrombin inhibitors, factor Xa inhibitors, factor VIIa inhibitors, integrin receptor antagonists, nitric oxide synthase inhibitors), with the aim of obtaining better activity, selectivity and oral bioavailability.

Acrylamide formation in food: a mechanistic perspective.

PubMed

Yaylayan, Varoujan A; Stadler, Richard H

2005-01-01

Earliest reports on the origin of acrylamide in food have confirmed asparagine as the main amino acid responsible for its formation. Available evidence suggests that sugars and other carbonyl compounds play a specific role in the decarboxylation process of asparagine, a necessary step in the generation of acrylamide. It has been proposed that Schiff base intermediate formed between asparagine and the sugar provides a low energy alternative to the decarboxylation from the intact Amadori product through generation and decomposition of oxazolidin-5-one intermediate, leading to the formation of a relatively stable azomethine ylide. Literature data indicate the propensity of such protonated ylides to undergo irreversible 1,2-prototropic shift and produce, in this case, decarboxylated Schiff bases which can easily rearrange into corresponding Amadori products. Decarboxylated Amadori products can either undergo the well known beta-elimination process initiated by the sugar moiety to produce 3-aminopropanamide and 1-deoxyglucosone or undergo 1,2-elimination initiated by the amino acid moiety to directly generate acrylamide. On the other hand, the Schiff intermediate can either hydrolyze and release 3-aminopropanamide or similarly undergo amino acid initiated 1,2-elimination to directly form acrylamide. Other thermolytic pathways to acrylamide--considered marginal at this stage--via the Strecker aldehyde, acrolein, and acrylic acid, are also addressed. Despite significant progress in the understanding of the mechanistic aspects of acrylamide formation, concrete evidence for the role of the different proposed intermediates in foods is still lacking.

Anti-trypanosomal activities and structural chemical properties of selected compound classes.

PubMed

Ponte-Sucre, Alicia; Bruhn, Heike; Schirmeister, Tanja; Cecil, Alexander; Albert, Christian R; Buechold, Christian; Tischer, Maximilian; Schlesinger, Susanne; Goebel, Tim; Fuß, Antje; Mathein, Daniela; Merget, Benjamin; Sotriffer, Christoph A; Stich, August; Krohne, Georg; Engstler, Markus; Bringmann, Gerhard; Holzgrabe, Ulrike

2015-02-01

Potent compounds do not necessarily make the best drugs in the market. Consequently, with the aim to describe tools that may be fundamental for refining the screening of candidates for animal and preclinical studies and further development, molecules of different structural classes synthesized within the frame of a broad screening platform were evaluated for their trypanocidal activities, cytotoxicities against murine macrophages J774.1 and selectivity indices, as well as for their ligand efficiencies and structural chemical properties. To advance into their modes of action, we also describe the morphological and ultrastructural changes exerted by selected members of each compound class on the parasite Trypanosoma brucei. Our data suggest that the potential organelles targeted are either the flagellar pocket (compound 77, N-Arylpyridinium salt; 15, amino acid derivative with piperazine moieties), the endoplasmic reticulum membrane systems (37, bisquaternary bisnaphthalimide; 77, N-Arylpyridinium salt; 68, piperidine derivative), or mitochondria and kinetoplasts (88, N-Arylpyridinium salt; 68, piperidine derivative). Amino acid derivatives with fumaric acid and piperazine moieties (4, 15) weakly inhibiting cysteine proteases seem to preferentially target acidic compartments. Our results suggest that ligand efficiency indices may be helpful to learn about the relationship between potency and chemical characteristics of the compounds. Interestingly, the correlations found between the physico-chemical parameters of the selected compounds and those of commercial molecules that target specific organelles indicate that our rationale might be helpful to drive compound design toward high activities and acceptable pharmacokinetic properties for all compound families.

Studies on quinolone antibacterials. V. Synthesis and antibacterial activity of chiral 5-amino-7-(4-substituted-3-amino-1-pyrrolidinyl)-6- fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acids and derivatives.

PubMed

Yoshida, T; Yamamoto, Y; Orita, H; Kakiuchi, M; Takahashi, Y; Itakura, M; Kado, N; Yasuda, S; Kato, H; Itoh, Y

1996-07-01

We previously demonstrated that 5-amino-7-(3-amino-1-pyrrolidinyl) -1-cyclopropyl-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (7) has strong in vitro antibacterial activity even against quinolone-resistant bacteria. We examined optimization of the 3-aminopyrrolidine moiety of 7 by introduction of C-alkyl (Me, Et, Pr, di-Me, cyclopropyl) and N-alkyl groups (Me, di-Me). C-Alkylation at the 4-position of the 3-aminopyrrolidine moiety enhanced in vitro and in vivo antibacterial activity. (S)-5-Amino-7-(7-amino-5-azaspiro[2.4]hept-5-yl)-1-cyclopropyl-pyr rolidinyl) -1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (15b) showed strong antibacterial activity (in vitro antibacterial activity including quinolone-resistant bacteria is 4 times more potent than that of ciprofloxacin (CPFX) (1); in vivo antibacterial activity is 1.5 to 20 times more potent than that of CPFX (1)) and reduced quinolone toxicity (free from both phototoxicity at a dosage of 30 mg/kg in guinea pigs (i.v.) and convulsion when coadministered with 4-biphenylacetic acid at a dosage of 20 micrograms in rats (i.c.v.)). Their selectivity between DNA topoisomerase II (derived from eukaryotic cells) and DNA gyrase (derived from bacterial cells) was about 3000-fold.

Determination of asparagine, glutamine and pyrrolidonecarboxylic acid in total enzymic hydrolysates of peptides and glycopeptides by gas–liquid chromatography

PubMed Central

Hediger, Hedy; Stevens, Richard L.; Brandenberger, Hans; Schmid, Karl

1973-01-01

A new procedure for the qualitative and quantitative determination of asparagine, glutamine and pyrrolidonecarboxylic acid in total enzymic hydrolysates of peptides and glycopeptides based on g.l.c. has been developed. Under the conditions of esterification and trifluoroacetylation N-trifluoroacetylaspartic acid mono-n-butyl ester was formed from asparagine and N-trifluoroacetylglutamic acid mono-n-butyl ester from both glutamine and pyrrolidonecarboxylic acid. To distinguish between the latter two compounds, the esterification was carried out at room temperature yielding 30% of esterified pyrrolidonecarboxylic acid but less than 1% of esterified glutamine. In extending the g.l.c. of amino acids, the previously unknown positions in the g.l.c. elution pattern of the following amino acids could also be reproducibly determined: carboxymethylcysteine, homoserine, hydroxylysine and ∈-methyl-lysine. Further, certain glycopeptides were investigated and the artifacts due to their carbohydrate moieties were determined. PMID:4733240

Structure Property Relationships of Carboxylic Acid Isosteres.

PubMed

Lassalas, Pierrik; Gay, Bryant; Lasfargeas, Caroline; James, Michael J; Tran, Van; Vijayendran, Krishna G; Brunden, Kurt R; Kozlowski, Marisa C; Thomas, Craig J; Smith, Amos B; Huryn, Donna M; Ballatore, Carlo

2016-04-14

The replacement of a carboxylic acid with a surrogate structure, or (bio)-isostere, is a classical strategy in medicinal chemistry. The general underlying principle is that by maintaining the features of the carboxylic acid critical for biological activity, but appropriately modifying the physicochemical properties, improved analogs may result. In this context, a systematic assessment of the physicochemical properties of carboxylic acid isosteres would be desirable to enable more informed decisions of potential replacements to be used for analog design. Herein we report the structure-property relationships (SPR) of 35 phenylpropionic acid derivatives, in which the carboxylic acid moiety is replaced with a series of known isosteres. The data set generated provides an assessment of the relative impact on the physicochemical properties that these replacements may have compared to the carboxylic acid analog. As such, this study presents a framework for how to rationally apply isosteric replacements of the carboxylic acid functional group.

Preparative separation of chlorogenic acid by centrifugal partition chromatography from highbush blueberry leaves (Vaccinium corymbosum L.).

PubMed

Kim, Sang-Min; Shang, Ya Fang; Um, Byung-Hun

2010-01-01

Blueberries (genus Vaccinium) have gained worldwide focus because of the high anthocyanin content of their fruits. In contrast, the leaves of blueberry have not attracted any attention, even though they contain large quantities of chlorogenic acid, a strong antioxidant compound. The aim of this investigation was the quantification and preparative isolation of chlorogenic acid (5-caffeoylquinic acid, 5-CQA) from blueberry leaves using a new separation scheme, centrifugal partition chromatography (CPC). A water fraction containing a high concentration of 5-CQA (14.5% of dry weight extract) was obtained by defatting a crude methanol extract from blueberry leaves. CPC was applied to isolate 5-CQA from this water fraction using a two-phase solvent system of ethyl acetate-ethanol-water at a volume ratio 4:1:5 (v/v/v). The flow-rate of mobile phase was 2 mL/min with the ascending mode while rotating at 1200 rpm. The eluate was monitored at 330 nm. The structure of chlorogenic acid in the CPC fraction was confirmed with HPLC, UV, ESI/MS and NMR spectra. The HPLC chromatogram showed that the fractions collected by CPC contained chlorogenic acid with 96% purity based on peak area percentage. The total amount of chlorogenic acid isolated from 0.5 g of a water fraction was 52.9 mg, corresponding to 10.6% of the water fraction. The isolated compound was identified successively as 5-CQA with MS (parent ion at m/z 355.1 [M + H](+)) and (1)H NMR spectra [caffeoyl moiety in the down field (δ 6.0-8.0 ppm) and quinic acid moiety in the up field (δ 2.0-5.5 ppm)]. 5-CQA was successfully isolated from blueberry leaves by the CPC method in a one-step procedure, indicating a further potential use for blueberry leaves. Copyright © 2010 John Wiley & Sons, Ltd.

Dioxaphosphorinane-constrained nucleic Acid dinucleotides as tools for structural tuning of nucleic acids.

PubMed

Catana, Dan-Andrei; Renard, Brice-Loïc; Maturano, Marie; Payrastre, Corinne; Tarrat, Nathalie; Escudier, Jean-Marc

2012-01-01

We describe a rational approach devoted to modulate the sugar-phosphate backbone geometry of nucleic acids. Constraints were generated by connecting one oxygen of the phosphate group to a carbon of the sugar moiety. The so-called dioxaphosphorinane rings were introduced at key positions along the sugar-phosphate backbone allowing the control of the six-torsion angles α to ζ defining the polymer structure. The syntheses of all the members of the D-CNA family are described, and we emphasize the effect on secondary structure stabilization of a couple of diastereoisomers of α,β-D-CNA exhibiting wether B-type canonical values or not.

Practical and Metal-Free Synthesis of Novel Enantiopure Amides Containing the Potentially Bioactive 5-Nitroimidazole Moiety.

PubMed

Spitz, Cédric; Mathias, Fanny; Giuglio-Tonolo, Alain Gamal; Terme, Thierry; Vanelle, Patrice

2016-11-04

We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1 H -imidazole to enantiomerically pure N - tert -butanesulfinimine. Then, the N - tert -butanesulfinyl-protected amine was easily deprotected under acidic conditions. Finally, the primary amine was coupled with different acid chlorides or acids to give the corresponding amides. The mild reaction conditions and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting 5-nitroimidazoles.

Solvent extraction system for plutonium colloids and other oxide nano-particles

DOEpatents

Soderholm, Lynda; Wilson, Richard E; Chiarizia, Renato; Skanthakumar, Suntharalingam

2014-06-03

The invention provides a method for extracting plutonium from spent nuclear fuel, the method comprising supplying plutonium in a first aqueous phase; contacting the plutonium aqueous phase with a mixture of a dielectric and a moiety having a first acidity so as to allow the plutonium to substantially extract into the mixture; and contacting the extracted plutonium with second a aqueous phase, wherein the second aqueous phase has a second acidity higher than the first acidity, so as to allow the extracted plutonium to extract into the second aqueous phase. The invented method facilitates isolation of plutonium polymer without the formation of crud or unwanted emulsions.

Facile and High-Yielding Synthesis of TAM Biradicals and Monofunctional TAM Radicals.

PubMed

Trukhin, Dmitry V; Rogozhnikova, Olga Yu; Troitskaya, Tatiana I; Vasiliev, Vladimir G; Bowman, Michael K; Tormyshev, Victor M

2016-04-01

Facile and high-yielding procedures for synthesis of monocarboxylic acid derivatives of triarylmethyl radicals (TAMs) were developed. Reaction of methyl thioglycolate with tris(2,3,5,6-tetrathiaaryl)methyl cation smoothly afforded the monosubstituted TAM derivative, which was hydrolyzed to a monocarboxylic acid, with the TAM moiety attached to thioglycolic acid via the sulfur atom. Alternatively, the diamagnetic tricarboxylic acid precursor of Finland trityl was transformed to a trimethyl ester and partially hydrolyzed under controlled conditions. The diester product was isolated and the remaining fractions were converted back to the trimethyl ester for production of more diester. The first representatives of TAM biradicals with different TAM cores and interspin distances were obtained by reaction of these new TAM monocaboxylic acids with N,N'-dimethylethylenediamine.

Effect of glycidyl methacrylate (GMA) incorporation on water uptake and conductivity of proton exchange membranes

NASA Astrophysics Data System (ADS)

Sproll, Véronique; Schmidt, Thomas J.; Gubler, Lorenz

2018-03-01

The aim of this work was to investigate how hygroscopic moieties like hydrolyzed glycidyl methacrylate (GMA) influence the properties of sulfonated polysytrene based proton exchange membranes (PEM). Therefore, several membranes were synthesized by electron beam treatment of the ETFE (ethylene-alt-tetrafluoroethylene) base film with a subsequent co-grafting of styrene and GMA at different ratios. The obtained membranes were sulfonated to introduce proton conducting groups and the epoxide moiety of the GMA unit was hydrolyzed for a better water absorption. The PEM was investigated regarding its structural composition, water uptake and through-plane conductivity. It could be shown that the density of sulfonic acid groups has a higher influence on the proton conductivity of the PEM than an increased water uptake.

A significant abiotic pathway for the formation of unknown nitrogen in nature

NASA Astrophysics Data System (ADS)

Jokic, A.; Schulten, H.-R.; Cutler, J. N.; Schnitzer, M.; Huang, P. M.

2004-03-01

The global nitrogen cycle is of prime importance in natural ecosystems. However, the origin and nature of up to one-half of total soil N remains obscure despite all attempts at elucidation. Our data provide, for the first time, unequivocal evidence that the promoting action of Mn (IV) oxide on the Maillard reaction (sugar-amino acid condensation) under ambient conditions results in the abiotic formation of heterocyclic N compounds, which are often referred to as unknown nitrogen, and of amides which are apparently the dominant N moieties in nature. The information presented is of fundamental significance in understanding the role of mineral colloids in abiotic transformations of organic N moieties, the incorporation of N in the organic matrix of fossil fuels, and the global N cycle.

Synthesis and structure-activity relationship of histone deacetylase (HDAC) inhibitors with triazole-linked cap group.

PubMed

Chen, Po C; Patil, Vishal; Guerrant, William; Green, Patience; Oyelere, Adegboyega K

2008-05-01

Histone deacetylase (HDAC) inhibition is a recent, clinically validated therapeutic strategy for cancer treatment. Small molecule HDAC inhibitors identified so far fall in to three distinct structural motifs: the zinc-binding group (ZBG), a hydrophobic linker, and a recognition cap group. Here we report the suitability of a 1,2,3-triazole ring as a surface recognition cap group-linking moiety in suberoylanilide hydroxamic acid-like (SAHA-like) HDAC inhibitors. Using "click" chemistry (Huisgen cycloaddition reaction), several triazole-linked SAHA-like hydroxamates were synthesized. Structure-activity relationship revealed that the position of the triazole moiety as well as the identity of the cap group markedly affected the in vitro HDAC inhibition and cell growth inhibitory activities of this class of compounds.

Conformationally constrained farnesoid X receptor (FXR) agonists: alternative replacements of the stilbene.

PubMed

Akwabi-Ameyaw, Adwoa; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Madauss, Kevin P; Marr, Harry B; Miller, Aaron B; Navas, Frank; Parks, Derek J; Spearing, Paul K; Todd, Dan; Williams, Shawn P; Wisely, G Bruce

2011-10-15

To further explore the optimum placement of the acid moiety in conformationally constrained analogs of GW 4064 1a, a series of stilbene replacements were prepared. The benzothiophene 1f and the indole 1g display the optimal orientation of the carboxylate for enhanced FXR agonist potency. Copyright © 2011 Elsevier Ltd. All rights reserved.

Design, synthesis and evaluation of a new Mn - Contrast agent for MR imaging of myocardium based on the DTPA-phenylpentadecanoic acid complex

NASA Astrophysics Data System (ADS)

Belyanin, Maxim L.; Stepanova, Elena V.; Valiev, Rashid R.; Filimonov, Victor D.; Usov, Vladimir Y.; Borodin, Oleg Y.; Ågren, Hans

2016-11-01

In the present paper we describe the first synthesis and evaluation of a novel Mn (II) complex (DTPA-PPDA Mn (II)) which contains a C-15 fatty acid moiety that has high affinity to the heart muscle. The complexation energy of DTPA-PPDA Mn (II) evaluated by quantum chemistry methodology indicates that it essentially exceeds the corresponding value for the known DTPA Mn (II) complex. Molecular docking revealed that the affinity of the designed complex to the heart-type transport protein H-FABP well exceeds that of lauric acid. Phantom experiments in low-field MRI the designed contrast agent provides MR imaging comparable to gadopentetic acid.

Investigating the chemical changes of chlorogenic acids during coffee brewing: conjugate addition of water to the olefinic moiety of chlorogenic acids and their quinides.

PubMed

Matei, Marius Febi; Jaiswal, Rakesh; Kuhnert, Nikolai

2012-12-12

Coffee is one of the most popular and consumed beverages in the world and is associated with a series of benefits for human health. In this study we focus on the reactivity of chlorogenic acids, the most abundant secondary metabolites in coffee, during the coffee brewing process. We report on the hydroxylation of the chlorogenic acid cinnamoyl substituent by conjugate addition of water to form 3-hydroxydihydrocaffeic acid derivatives using a series of model compounds including monocaffeoyl and dicaffeoylquinic acids and quinic acid lactones. The regiochemistry of conjugate addition was established based on targeted tandem MS experiments. Following conjugate addition of water a reversible water elimination yielding cis-cinnamoyl derivatives accompanied by acyl migration products was observed in model systems. We also report the formation of all of these derivatives during the coffee brewing process.

Stabilization Effect of Amino Acid Side Chains in Peptide Assemblies on Graphite Studied by Scanning Tunneling Microscopy.

PubMed

Guo, Yuanyuan; Hou, Jingfei; Zhang, Xuemei; Yang, Yanlian; Wang, Chen

2017-04-19

An analysis is presented of the effects of amino acid side chains on peptide assemblies in ambient conditions on a graphite surface. The molecularly resolved assemblies of binary peptides are examined with scanning tunneling microscopy. A comparative analysis of the assembly structures reveals that the lamellae width has an appreciable dependence on the peptide sequence, which could be considered as a manifestation of a stabilizing effect of side-chain moieties of amino acids with high (phenylalanine) and low (alanine, asparagine, histidine and aspartic acid) propensities for aggregation. These amino acids are representative for the chemical structures involving the side chains of charged (histidine and aspartic acid), aromatic (phenylalanine), hydrophobic (alanine), and hydrophilic (asparagine) amino acids. These results might provide useful insight for understanding the effects of sequence on the assembly of surface-bound peptides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nanoporous polysulfone membranes via a degradable block copolymer precursor for redox flow batteries

DOE PAGES

Gindt, Brandon P.; Abebe, Daniel G.; Tang, Zhijiang J.; ...

2016-02-16

In this study, nanoporous polysulfone (PSU) membranes were fabricated via post-hydrolysis of polylactide (PLA) from PLA–PSU–PLA triblock copolymer membranes. The PSU scaffold was thermally crosslinked before sacrificing PLA blocks. The resulting nanopore surface was chemically modified with sulfonic acid moieties. The membranes were analyzed and evaluated as separators for vanadium redox flow batteries. Nanoporous PSU membranes prepared by this new method and further chemically modified to a slight degree exhibited unique behavior with respect to their ionic conductivity when exposed to solutions of increasing acid concentration.

The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2 family protein-protein interactions.

PubMed

Touré, B Barry; Miller-Moslin, Karen; Yusuff, Naeem; Perez, Lawrence; Doré, Michael; Joud, Carol; Michael, Walter; DiPietro, Lucian; van der Plas, Simon; McEwan, Michael; Lenoir, Francois; Hoe, Madelene; Karki, Rajesh; Springer, Clayton; Sullivan, John; Levine, Kymberly; Fiorilla, Catherine; Xie, Xiaoling; Kulathila, Raviraj; Herlihy, Kara; Porter, Dale; Visser, Michael

2013-02-14

Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263.

Photoactive ligands probing the sweet taste receptor. Design and synthesis of highly potent diazirinyl D-phenylalanine derivatives.

PubMed

Masuda, Katsuyoshi; Koizumi, Ayako; Misaka, Takumi; Hatanaka, Yasumaru; Abe, Keiko; Tanaka, Takaharu; Ishiguro, Masaji; Hashimoto, Makoto

2010-02-01

Some D-amino acids such as d-tryptophan and D-phenylalanine are well known as naturally-occurring sweeteners. Photoreactive D-phenylalanine derivatives containing trifluoromethyldiazirinyl moiety at 3- or 4-position of phenylalanine, were designed as sweeteners for functional analysis with photoaffinity labeling. The trifluoromethyldiazirinyl D-phenylalanine derivatives were prepared effectively with chemo-enzymatic methods using L-amino acid oxidase and were found to have potent activity toward the human sweet taste receptor. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

A chiral Brønsted acid-catalyzed highly enantioselective Mannich-type reaction of α-diazo esters with in situ generated N-acyl ketimines.

PubMed

Unhale, Rajshekhar A; Sadhu, Milon M; Ray, Sumit K; Biswas, Rayhan G; Singh, Vinod K

2018-04-03

A chiral phosphoric acid-catalyzed asymmetric Mannich-type reaction of α-diazo esters with in situ generated N-acyl ketimines, derived from 3-hydroxyisoindolinones has been demonstrated in this communication. A variety of isoindolinone-based α-amino diazo esters bearing a quaternary stereogenic center were afforded in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). Furthermore, the synthetic utility of the products has been depicted by the hydrogenation of the diazo moiety of adducts.

Proton exchange membranes for application in fuel cells: grafted silica/SPEEK nanocomposite elaboration and characterization.

PubMed

Reinholdt, Marc X; Kaliaguine, Serge

2010-07-06

Hydrogen technologies and especially fuel cells are key components in the battle to find alternate sources of energy to the highly polluting and economically constraining fossil fuels in an aim to preserve the environment. The present paper shows the synthesis of surface functionalized silica nanoparticles, which are used to prepare grafted silica/SPEEK nanocomposite membranes. The nanoparticles are grafted either with hexadecylsilyl or aminopropyldimethylsilyl moieties or both. The synthesized particles are analyzed using XRD, NMR, TEM, and DLS to collect information on the nature of the particles and the functional groups, on the particle sizes, and on the hydrophilic/hydrophobic character. The composite membranes prepared using the synthesized particles and two SPEEK polymers with sulfonation degrees of 69.4% and 85.0% are characterized for their proton conductivity and water uptake properties. The corresponding curves are very similar for the composites prepared with both polymers and the nanoparticles bearing the two functional groups. The composites prepared with the nanoparticles bearing solely the aminopropyldimethylsilyl moiety exhibit lower conductivity and water uptake, possibly due to higher interaction of the polymer sulfonic acid sites with the amine groups. The composites prepared with the nanoparticles bearing solely the hexadecylsilyl moiety were not further investigated because of very high particles segregation. A study of the proton conductivity as a function of temperature was performed on selected membranes and showed that nanocomposites made with nanoparticles bearing both functional moieties have a higher conductivity at higher temperatures.

Linear and branched alkyl-esters and amides of gallic acid and other (mono-, di- and tri-) hydroxy benzoyl derivatives as promising anti-HCV inhibitors.

PubMed

Rivero-Buceta, Eva; Carrero, Paula; Doyagüez, Elisa G; Madrona, Andrés; Quesada, Ernesto; Camarasa, María José; Peréz-Pérez, María Jesús; Leyssen, Pieter; Paeshuyse, Jan; Balzarini, Jan; Neyts, Johan; San-Félix, Ana

2015-03-06

Linear and branched compounds that contain two, three or five units of galloyl (3,4,5-trihydroxybenzoyl) or its isomer 2,3,4-trihydroxybenzoyl, as well as other mono- or dihydroxybenzoyl moieties have been synthesized. These molecules have been evaluated for their in vitro inhibitory effects against a wide panel of viruses showing preferential activity against HIV and HCV. Our structure-activity relationship studies demonstrated that the 2,3,4-trihydroxybenzoyl moiety provides better antiviral activities than the galloyl (3,4,5-trihydroxybenzoyl) moiety that is present in natural green tea catechins. This observation can be of interest for the further rational exploration of compounds with anti-HCV/HIV properties. The most notable finding with respect to HIV is that the tripodal compounds 43 and 45, with three 2,3,4-trihydroxybenzoyl moieties, showed higher activities than linear compounds with only one or two. With respect to HCV, the linear compounds, 52 and 41, containing a 12 polymethylene chain and two 2,3 di- or 2,3,4 tri-hydroxybenzoyl groups respectively at the ends of the molecule showed good antiviral efficiency. Furthermore, the anti-HCV activity of both compounds was observed at concentrations well below the cytotoxicity threshold. A representative member of these compounds, 41, showed that the anti-HCV activity was largely independent of the genetic make-up of the HCV subgenomic replicon and cell lines used. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Tuning the acid/base properties of nanocarbons by functionalization via amination.

PubMed

Arrigo, Rosa; Hävecker, Michael; Wrabetz, Sabine; Blume, Raoul; Lerch, Martin; McGregor, James; Parrott, Edward P J; Zeitler, J Axel; Gladden, Lynn F; Knop-Gericke, Axel; Schlögl, Robert; Su, Dang Sheng

2010-07-21

The surface chemical properties and the electronic properties of vapor grown carbon nanofibers (VGCNFs) have been modified by treatment of the oxidized CNFs with NH(3). The effect of treatment temperature on the types of nitrogen functionalities introduced was evaluated by synchrotron based X-ray photoelectron spectroscopy (XPS), while the impact of the preparation methods on the surface acid-base properties was investigated by potentiometric titration, microcalorimetry, and zeta potential measurements. The impact of the N-functionalization on the electronic properties was measured by THz-Time Domain spectroscopy. The samples functionalized via amination are characterized by the coexistence of acidic and basic O and N sites. The population of O and N species is temperature dependent. In particular, at 873 K nitrogen is stabilized in substitutional positions within the graphitic structure, as heterocyclic-like moieties. The surface presents heterogeneously distributed and energetically different basic sites. A small amount of strong basic sites gives rise to a differential heat of CO(2) adsorption of 150 kJ mol(-1). However, when functionalization is carried out at 473 K, nitrogen moieties with basic character are introduced and the maximum heat of adsorption is significantly lower, at approximately 90 kJ mol(-1). In the latter sample, energetically different basic sites coexist with acidic oxygen groups introduced during the oxidative step. Under these conditions, a bifunctional acidic and basic surface is obtained with high hydrophilic character. N-functionalization carried out at higher temperature changes the electronic properties of the CNFs as evaluated by THz-TDS. The functionalization procedure presented in this work allows high versatility and flexibility in tailoring the surface chemistry of nanocarbon material to specific needs. This work shows the potential of the N-containing nanocarbon materials obtained via amination in catalysis as well as electronic device materials.

Nanocomposites of phosphonic-acid-functionalized polyethylenes with inorganic quantum dots.

PubMed

Rünzi, Thomas; Baier, Moritz C; Negele, Carla; Krumova, Marina; Mecking, Stefan

2015-01-01

Insertion of diethyl vinyl phosphonates and free vinyl phosphonic acid, respectively, into [(P^O)Pd(Me)(dmso)] ((P^O) = κ(2)-P,O-Ar2PC6H4SO2O with Ar = 2-MeOC6H4) (1-dmso) occurs in a 2,1- as well as 1,2-fashion, to form a four-and a five-membered chelate [(P^O)Pd{κ(2)-C,O-CH(P(O)(OR)2)CH2CH3}] and [(P^O)Pd{κ(2)-C,O-CH2CH(P(O)(OR)2)CH3}] (R = H, Et). No decomposition or other reactions of 1 by free phosphonic acid moieties occur. Copolymerization in a pressure reactor by 1-dmso yields linear random poly(ethylene-co-diethyl vinyl phosphonate) and poly(ethylene-co-vinyl phosphonic acid). In these copolymerizations, reversible coordination of the phosphonate moieties of free monomer as well as chelate formation by incorporated monomer retards chain growth as also evidenced by relative binding studies of diethyl phosphonate towards 1. Post-polymerization emulsification of poly(ethylene-co-vinyl phosphonic acid) together with CdSe/CdS quantum dots (QDs) yields submicron (ca. 50 nm from dynamic light scattering (DLS) and transmission electron microscopy (TEM)) polymer particles with the QDs embedded in the functionalized polyethylene in a nonaggregated fashion. This embedding benefits the fluorescence behavior in terms of continuous emission and life-time as revealed by wide-field fluorescence measurements. These composite particle dispersions are employed as a ″masterbatch" together with an aqueous high density polyethylene (HDPE) dispersion to generate thin films (by spin-coating) and bulk materials (from the melt), respectively, in which the inorganic nanoparticles remain highly disperse. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ratiometric Near-Infrared Fluorescent Probes Based On Through-Bond Energy Transfer and π-Conjugation Modulation between Tetraphenylethene and Hemicyanine Moieties for Sensitive Detection of pH Changes in Live Cells.

PubMed

Wang, Jianbo; Xia, Shuai; Bi, Jianheng; Fang, Mingxi; Mazi, Wafa; Zhang, Yibin; Conner, Nathan; Luo, Fen-Tair; Lu, H Peter; Liu, Haiying

2018-04-18

In this paper, we present three ratiometric near-infrared fluorescent probes (A-C) for accurate, ratiometric detection of intracellular pH changes in live cells. Probe A consists of a tetraphenylethene (TPE) donor and near-infrared hemicyanine acceptor in a through-bond energy transfer (TBET) strategy, while probes B and C are composed of TPE and hemicyanine moieties through single and double sp 2 carbon-carbon bond connections in a π-conjugation modulation strategy. The specific targeting of the probes to lysosomes in live cells was achieved by introducing morpholine residues to the hemicyanine moieties to form closed spirolactam ring structures. Probe A shows aggregation-induced emission (AIE) property at neutral or basic pH, while probes B and C lack AIE properties. At basic or neutral pH, the probes only show fluorescence of TPE moieties with closed spirolactam forms of hemicyanine moieties, and effectively avoid blind fluorescence imaging spots, an issue which typical intensity-based pH fluorescent probes encounter. Three probes show ratiometric fluorescence responses to pH changes from 7.0 to 3.0 with TPE fluorescence decreases and hemicyanine fluorescence increases, because acidic pH makes the spirolactam rings open to enhance π-conjugation of hemicyanine moieties. However, probe A shows much more sensitive ratiometric fluorescence responses to pH changes from 7.0 to 3.0 with remarkable ratio increase of TPE fluorescence to hemicyanine fluorescence up to 238-fold than probes B and C because of its high efficiency of energy transfer from TPE donor to the hemicyanine acceptor in the TBET strategy. The probe offers dual Stokes shifts with a large pseudo-Stokes shift of 361 nm and well-defined dual emissions, and allows for colocalization of the imaging readouts of visible and near-infrared fluorescence channels to achieve more precisely double-checked ratiometric fluorescence imaging. These platforms could be employed to develop a variety of novel ratiometric fluorescent probes for accurate detection of different analytes in applications of chemical and biological sensing, imaging, and diagnostics by introducing appropriate sensing ligands to hemicyanine moieties to form on-off spirolactam switches.

Sialylated Receptor Setting Influences Mycoplasma pneumoniae Attachment and Gliding Motility.

PubMed

Williams, Caitlin R; Chen, Li; Driver, Ashley D; Arnold, Edward A; Sheppard, Edward S; Locklin, Jason; Krause, Duncan C

2018-06-08

Mycoplasma pneumoniae is a common cause of human respiratory tract infections, including bronchitis and atypical pneumonia. M. pneumoniae binds glycoprotein receptors having terminal sialic acid residues via the P1 adhesin protein. Here we explored the impact of sialic acid presentation on M. pneumoniae adherence and gliding on surfaces coated with sialylated glycoproteins, or chemically functionalized with α-2,3- and α-2,6-sialyllactose ligated individually or in combination to a polymer scaffold in precisely controlled densities. In both models, gliding required a higher receptor density threshold than adherence, and receptor density influenced gliding frequency but not gliding speed. However, very high densities of α-2,3-sialyllactose actually reduced gliding frequency over peak levels observed at lower densities. Both α-2,3- and α-2,6-sialyllactose supported M. pneumoniae adherence, but gliding was only observed on the former. Finally, gliding on α-2,3-sialyllactose was inhibited on surfaces also conjugated with α-2,6-sialyllactose, suggesting that both moieties bind P1 despite the inability of the latter to support gliding. Our results indicate that the nature and density of host receptor moieties profoundly influences M. pneumoniae gliding, which could affect pathogenesis and infection outcome. Furthermore, precise functionalization of polymer scaffolds shows great promise for further analysis of sialic acid presentation and M. pneumoniae adherence and gliding. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

Improvement of kynurenine aminotransferase-II inhibitors guided by mimicking sulfate esters.

PubMed

Jayawickrama, Gayan S; Nematollahi, Alireza; Sun, Guanchen; Church, William Bret

2018-01-01

The mammalian kynurenine aminotransferase (KAT) enzymes are a family of related isoforms that are pyridoxal 5'-phosphate-dependent, responsible for the irreversible transamination of kynurenine to kynurenic acid. Kynurenic acid is implicated in human diseases such as schizophrenia where it is found in elevated levels and consequently KAT-II, as the isoform predominantly responsible for kynurenic acid production in the brain, has been targeted for the development of specific inhibitors. One class of compounds that have also shown inhibitory activity towards the KAT enzymes are estrogens and their sulfate esters. Estradiol disulfate in particular is very strongly inhibitory and it appears that the 17-sulfate makes a significant contribution to its potency. The work here demonstrates that the effect of this moiety can be mirrored in existing KAT-II inhibitors, from the development of two novel inhibitors, JN-01 and JN-02. Both inhibitors were based on NS-1502 (IC50: 315 μM), but the deliberate placement of a sulfonamide group significantly improved the potency of JN-01 (IC50: 73.8 μM) and JN-02 (IC50: 112.8 μM) in comparison to the parent compound. This 3-4 fold increase in potency shows the potential of these moieties to be accommodated in the KAT-II active site and the effect they can have on improving inhibitors, and the environments in the KAT-II have been suitably modelled using docking calculations.

Effects of introducing a single charged residue into the phenylalanine clamp of multimeric anthrax protective antigen.

PubMed

Janowiak, Blythe E; Fischer, Audrey; Collier, R John

2010-03-12

Multimeric pores formed in the endosomal membrane by the Protective Antigen moiety of anthrax toxin translocate the enzymatic moieties of the toxin to the cytosolic compartment of mammalian cells. There is evidence that the side chains of the Phe(427) residues come into close proximity with one another in the lumen of the pore and form a structure, termed the Phe clamp, that catalyzes the translocation process. In this report we describe the effects of replacing Phe(427) in a single subunit of the predominantly heptameric pore with a basic or an acidic amino acid. Incorporating any charged residue at this position inhibited cytotoxicity >or=1,000-fold in our standard assay and caused strong inhibition of translocation in a planar phospholipid bilayer system. His and Glu were the most strongly inhibitory residues, ablating both cytotoxicity and translocation. Basic residues at position 427 prevented the Phe clamp from interacting with a translocation substrate to form a seal against the passage of ions and accelerated dissociation of the substrate from the pore. Acidic residues, in contrast, allowed the seal to form and the substrate to remain firmly bound, but blocked its passage, perhaps via electrostatic interactions with the positively charged N-terminal segment. Our findings are discussed in relation to the role of the Phe clamp in a Brownian ratchet model of translocation.

Ameliorating Effects of Sulfonylurea Drugs on Insulin Resistance in Otsuka Long-Evans Tokushima Fatty Rats

PubMed Central

Park, Jeong-Kwon; Kim, Sang-Pyo

2008-01-01

OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium (KATP) channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of KATP channels, insulin receptor β-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that KATP-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on KATP channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects. PMID:20157388

Ameliorating effects of sulfonylurea drugs on insulin resistance in Otsuka long-evans Tokushima Fatty rats.

PubMed

Park, Jeong-Kwon; Kim, Sang-Pyo; Song, Dae-Kyu

2008-02-01

OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium (K(ATP)) channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of K(ATP) channels, insulin receptor beta-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that K(ATP)-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on K(ATP) channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects.

Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L (CbpL) Contributing to Pneumococcal Pathogenesis

PubMed Central

Gutiérrez-Fernández, Javier; Saleh, Malek; Alcorlo, Martín; Gómez-Mejía, Alejandro; Pantoja-Uceda, David; Treviño, Miguel A.; Voß, Franziska; Abdullah, Mohammed R.; Galán-Bartual, Sergio; Seinen, Jolien; Sánchez-Murcia, Pedro A.; Gago, Federico; Bruix, Marta; Hammerschmidt, Sven; Hermoso, Juan A.

2016-01-01

The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca2+-binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp_Lipoprotein domain. Our structural and infection assays indicate an important role of the whole multimodular protein allowing both to locate CbpL at specific places on the cell wall and to interact with host components in order to facilitate pneumococcal lung infection and transmigration from nasopharynx to the lungs and blood. CbpL implication in both resistance against killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein as relevant among the pathogenic arsenal of the pneumococcus. PMID:27917891

Spiroketalcarminic Acid, a Novel Minor Anthraquinone Pigment in Cochineal Extract Used in Food Additives.

PubMed

Ito, Yusai; Harikai, Naoki; Ishizuki, Kyoko; Shinomiya, Kazufusa; Sugimoto, Naoki; Akiyama, Hiroshi

2017-09-01

Cochineal extract prepared from the scale insect Dactylopus coccus (American cochineal) has been used as a natural red dye for food, cosmetics, and pharmaceuticals. The major pigment in cochineal extract is carminic acid (CA), an anthraquinone glucoside, and several minor pigments have been previously reported. Our investigation aimed at establishing the safety of cochineal dye products using ultra performance liquid chromatography-photo diode array-electrospray ionization-time of flight (UPLC-PDA-ESI-TOF)/MS found an unknown minor pigment, spiroketalcarminic acid (1), in three commercial cochineal extract samples; cochineal extract used in food additives, carmine that is an aluminum salt of cochineal extract used as natural dye, and a research reagent of CA. The purification of 1 from cochineal extract involved sequential chromatographic techniques, including preparative reversed-phase HPLC. Two dimensional (2D)-NMR and mass analyses established the structure of 1 to be a novel anthraquinone with an unusual 6,5-spiroketal system instead of the C-glucosyl moiety of CA. The absolute stereochemistry of the spiroketal moiety in 1 was determined by nuclear Overhauser effect spectroscopy (NOESY) correlations and optical rotation. No data corresponding to 1 had previously been reported for extracts of dried cochineal insects and traditional art products dyed with cochineal extract, indicating that 1 is likely produced during the preparation of commercial cochineal extract.

Conserved phosphoryl transfer mechanisms within kinase families and the role of the C8 proton of ATP in the activation of phosphoryl transfer

PubMed Central

2012-01-01

Background The kinome is made up of a large number of functionally diverse enzymes, with the classification indicating very little about the extent of the conserved kinetic mechanisms associated with phosphoryl transfer. It has been demonstrated that C8-H of ATP plays a critical role in the activity of a range of kinase and synthetase enzymes. Results A number of conserved mechanisms within the prescribed kinase fold families have been identified directly utilizing the C8-H of ATP in the initiation of phosphoryl transfer. These mechanisms are based on structurally conserved amino acid residues that are within hydrogen bonding distance of a co-crystallized nucleotide. On the basis of these conserved mechanisms, the role of the nucleotide C8-H in initiating the formation of a pentavalent intermediate between the γ-phosphate of the ATP and the substrate nucleophile is defined. All reactions can be clustered into two mechanisms by which the C8-H is induced to be labile via the coordination of a backbone carbonyl to C6-NH2 of the adenyl moiety, namely a "push" mechanism, and a "pull" mechanism, based on the protonation of N7. Associated with the "push" mechanism and "pull" mechanisms are a series of proton transfer cascades, initiated from C8-H, via the tri-phosphate backbone, culminating in the formation of the pentavalent transition state between the γ-phosphate of the ATP and the substrate nucleophile. Conclusions The "push" mechanism and a "pull" mechanism are responsible for inducing the C8-H of adenyl moiety to become more labile. These mechanisms and the associated proton transfer cascades achieve the proton transfer via different family-specific conserved sets of amino acids. Each of these mechanisms would allow for the regulation of the rate of formation of the pentavalent intermediate between the ATP and the substrate nucleophile. Phosphoryl transfer within kinases is therefore a specific event mediated and regulated via the coordination of the adenyl moiety of ATP and the C8-H of the adenyl moiety. PMID:22397702

Development of Bone Targeting Drugs.

PubMed

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Mackenzie, William G; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

2017-06-23

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca 2+ . The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.

Development of Bone Targeting Drugs

PubMed Central

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J.; Mackenzie, William G.; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

2017-01-01

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca2+. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments. PMID:28644392

Some Physical Properties of Protein Moiety of Alkali-Extracted Tea Polysaccharide Conjugates Were Shielded by Its Polysaccharide.

PubMed

Chen, Xiaoqiang; Song, Wei; Zhao, Jin; Zhang, Zhifa; Zhang, Yuntian

2017-05-31

Polysaccharide conjugates were alkali-extracted from green tea (TPC-A). Although it contained 11.80% covalently binding proteins, TPC-A could not bind to the Coomassie Brilliant Blue dyes G250 and R250. TPC-A had no expected characteristic absorption peak of protein in the UV-vis spectrum scanning in the range of 200-700 nm. The UV-vis wavelength of 280 nm was not suitable to detect the presence of the protein portion of TPC-A. The zeta potential of TPC-A merely presented the negative charge properties of polysaccharides instead of the acid-base property of its protein section across the entire pH range. Furthermore, TPC-A was more stable when the pH of solution exceeded 4.0. In addition, no precipitation or haze was generated in the TPC-A/(-)-epigallocatechin gallate (EGCG) mixtures during 12 h storage. TPC-A has emulsifying activity, which indicated that its protein moiety formed hydrophobic groups. Thus, it was proposed that some physical properties of TPC-A protein were shielded by its olysaccharide, since the protein moiety was wrapped by its polysaccharide chains.

One pot synthesis, X-ray crystal structure of 2-(2‧-hydroxyphenyl)oxazolo[4,5-b]pyridine derivatives and studies of their optical properties

NASA Astrophysics Data System (ADS)

Briseño-Ortega, Horacio; Juárez-Guerra, Lizbeth; Rojas-Lima, Susana; Mendoza-Huizar, Luis Humberto; Vázquez-García, Rosa A.; Farfán, Norberto; Arcos-Ramos, Rafael; Santillan, Rosa; López-Ruiz, Heralio

2018-04-01

A series of five 2-(2-hydroxyphenyl)oxazolo [4,5-b]pyridines (HPOP) (3a-e), where four are novel, were synthesized by a mild, one pot, phenylboronic acid-NaCN catalyzed reaction. Spectroscopic characterization and photophysical properties of these compounds are reported. Absorption and excitation spectra of the compounds were dependent on the substituents in the phenyl ring. Fluorescence quantum yields (0.009-0.538) were associated with the donor strength and the position of the substituents. Also, DFT analysis allowed us to determine the contribution of diethylamino and methoxy moieties to the π-system, which is in agreement with the experimental data analyzed in solution and by cyclic voltammetry. The results obtained in the solid state by single-crystal X-ray diffraction experiments indicate that, the quasi-planarity envisioned for the explored compounds is present, supporting the hypothesis that both the H-bonding of a hydroxyl group to the Cdbnd N moiety and a donor groups such as diethylamino and methoxy moieties favor an electronic communication. Due to the facile synthesis and their photophysical properties, the novel HPOP 3a-e have potential application as organic semiconductors.

Engineering an Escherichia coli platform to synthesize designer biodiesels.

PubMed

Wierzbicki, Michael; Niraula, Narayan; Yarrabothula, Akshitha; Layton, Donovan S; Trinh, Cong T

2016-04-20

Biodiesels, fatty acid esters (FAEs), can be synthesized by condensation of fatty acid acyl CoAs and alcohols via a wax ester synthase in living cells. Biodiesels have advantageous characteristics over petrodiesels such as biodegradability, a higher flash point, and less emission. Controlling fatty acid and alcohol moieties are critical to produce designer biodiesels with desirable physiochemical properties (e.g., high cetane number, low kinematic viscosity, high oxidative stability, and low cloud point). Here, we developed a flexible framework to engineer Escherichia coli cell factories to synthesize designer biodiesels directly from fermentable sugars. In this framework, we designed each FAE pathway as a biodiesel exchangeable production module consisting of acyl CoA, alcohol, and wax ester synthase submodules. By inserting the FAE modules in an engineered E. coli modular chassis cell, we generated E. coli cell factories to produce targeted biodiesels (e.g., fatty acid ethyl (FAEE) and isobutyl (FAIbE) esters) with tunable and controllable short-chain alcohol moieties. The engineered E. coli chassis carrying the FAIbE production module produced 54mg/L FAIbEs with high specificity, accounting for>90% of the total synthesized FAEs and ∼4.7 fold increase in FAIbE production compared to the wildtype. Fed-batch cultures further improved FAIbE production up to 165mg/L. By mixing ethanol and isobutanol submodules, we demonstrated controllable production of mixed FAEEs and FAIbEs. We envision the developed framework offers a flexible, alternative route to engineer designer biodiesels with tunable and controllable properties using biomass-derived fermentable sugars. Copyright © 2016 Elsevier B.V. All rights reserved.

Structure-wise discrimination of adenine and guanine by proteins on the basis of their nonbonded interactions.

PubMed

Usha, S; Selvaraj, S

2015-01-01

We have analyzed the nonbonded interactions of the structurally similar moieties, adenine and guanine forming complexes with proteins. The results comprise (a) the amino acid-ligand atom preferences, (b) solvent accessibility of ligand atoms before and after complex formation with proteins, and (c) preferred amino acid residue atoms involved in the interactions. We have observed that the amino acid preferences involved in the hydrogen bonding interactions vary for adenine and guanine. The structural variation between the purine atoms is clearly reflected by their burial tendency in the solvent environment. Correlation of the mean amino acid preference values show the variation that exists between adenine and guanine preferences of all the amino acid residues. All our observations provide evidence for the discriminating nature of the proteins in recognizing adenine and guanine.

Conversion of the LXR-agonist TO-901317--from inverse to normal modulation of gamma-secretase by addition of a carboxylic acid and a lipophilic anchor.

PubMed

Narlawar, Rajeshwar; Baumann, Karlheinz; Czech, Christian; Schmidt, Boris

2007-10-01

TO-901317, a LXR agonist, is an inverse modulator of Alzheimer's disease associated gamma-secretase. We synthesized TO-901317 analogous compound but replaced the hexafluorocarbinol moiety by an oxyacetic acid functionality and hypothesized that the replacement would change the mode of action from an inverse modulation to normal modulation of gamma-secretase. As anticipated, acid 9 was found to be an effective modulator of gamma-secretase and displayed activity at low micromolar concentration. This significant modification can be applied to several inverse gamma-secretase modulators. Such modulators may preserve the cleavage of other gamma-secretase substrates such as Notch.

Novel fluoro copolymers for 157-nm photoresists: a progress report

NASA Astrophysics Data System (ADS)

Hohle, Christoph; Hien, Stefan; Eschbaumer, Christian; Rottstegge, Joerg; Sebald, Michael

2002-07-01

Several fluoro-substituted polymers consisting of acid cleavable methacryoic or cinnamic acid tert.-butyl ester compounds copolymerized with maleic acid anhydride derivatives were synthesized by radical copolymerization. Vacuum ultraviolet transmission measurements of the samples reveal absorbances down to 5micrometers -1 despite of the strongly absorbing anhydride moiety which serves as silylation anchor for the application of the Chemical Amplification of Resist Lines (CARL) process, one of the promising approaches for sub-90nm pattern fabrication. Some of the samples exhibit resolutions down to 110nm dense at 157nm exposure using an alternating phase shift mask. The feasibility of the CARL principle including the silylation reaction after development has been demonstrated with selected fluorinated polymer samples.

Peptides whose uptake by cells is controllable

DOEpatents

Jiang, Tao; Olson, Emilia S.; Whitney, Michael; Tsien, Roger

2015-07-07

A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.

One new galloyl glycoside from fresh leaves of Psidium guajava L.

PubMed

Shu, Ji-cheng; Chou, Gui-xin; Wang, Zheng-tao

2010-03-01

To investigate the chemical constituents of Psidium Guajava L, the EtOH/H2O extract of the fresh leaves was subjected to various chromatography. Five constituents with galloyl moiety were isolated and elucidated as 1-O-(1, 2-propanediol)-6-O-galloyl-beta-D-glucopyranoside (1), gallic acid (2), ellagic acid (3), ellagic acid-4-O-beta-D-glucopyranoside (4) and quercetin-3-O-(6"-galloyl) beta-D-galactopyranoside (5) by spectroscopic methods, including 2D NMR and HR-ESI-MS spectrometry as well as by comparison with published data. Compounds 4 and 5 were obtained from P. guajava for the first time, and compound 1 is a new polyhydroxyl compound.

Peptides whose uptake by cells is controllable

DOEpatents

Jiang, Tao [San Diego, CA; Olson, Emilia S [La Jolla, CA; Whitney, Michael [San Diego, CA; Tsien, Roger [La Jolla, CA

2011-07-26

A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruslin, Farah bt; Yamin, Bohari M.

A flake-like crystalline salt was obtained from the reaction of ferrocene, oxalic acid and ammonium thiocyanate in ethanol The elemental analysis and spectroscopic data were in agreement with the preliminary X-ray molecular structure. The compound consists of four ferrocenium moieties and a counter anion consisting of two (tetraisothiocyanato)iron(III) linked by an oxalato bridging group in such a way that both iron central atoms adopt octahedral geometries.

HPLC analysis of functionalized poly(amidoamine) dendrimers and the interaction between a folate-dendrimer conjugate and folate binding protein.

PubMed

Shi, Xiangyang; Bi, Xiangdong; Ganser, T Rose; Hong, Seungpyo; Myc, Lukasz A; Desai, Ankur; Holl, Mark M Banaszak; Baker, James R

2006-07-01

Poly(amidoamine) (PAMAM) dendrimers of different generations with carboxyl, acetyl, and hydroxyl terminal groups and a folic acid (FA)-dendrimer conjugate were separated and analyzed using reverse-phase high performance liquid chromatography (HPLC). Analysis of both the individual PAMAM derivatives and the separation of mixed generations can be achieved using a linear gradient 0-50% acetonitrile (ACN) (balance water) within 40 min. We also show that PAMAMs with defined acetylation and carboxylation degrees can be analyzed using HPLC. Furthermore, a generation 5 dendrimer-FA conjugate (G5.75Ac-FA4; Ac denotes acetyl) was analyzed and its specific binding with a bovine folic acid binding protein (FBP) was monitored. The HPLC and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results indicate the formation of three complexes after the binding of G5.75Ac-FA4 with FBP. Dendrimers with FA moieties show much higher specific binding capability with FBP than those without FA moieties. Findings from this study indicate that HPLC is an effective technique not only for characterization and separation of functionalized PAMAM dendrimers and conjugates but also for investigation of the interaction between dendrimers and biomolecules.

Two Dihydroxo-Bridged Plutonium(IV) Nitrate Dimers and Their Relevance to Trends in Tetravalent Ion Hydrolysis and Condensation

DOE PAGES

Knope, Karah E.; Skanthakumar, S.; Soderholm, L.

2015-10-13

We report the room temperature synthesis and structural characterization of a μ2-hydroxobridged PuIV dimer obtained from an acidic, nitric acid solution. The discrete Pu 2(OH) 2(NO 3) 6(H 2O) 4 moiety crystallized with two distinct crystal structures, (1) [Pu 2(OH) 2(NO 3) 6(H 2O) 4] 2·11H 2O and (2) Pu 2(OH) 2(NO 3) 6(H 2O) 4·2H 2O, which differ primarily in the number of incorporated water molecules. High-energy X-ray scattering (HEXS) data obtained from the mother liquor showed evidence of a correlation at 3.7(10) Å but only after concentration of the stock solution. This distance is consistent with the dihydroxo-bridgedmore » distance of 3.799(1) Å seen in the solid-state structure as well as with the known Pu-Pu distance in PuO 2. The structural characterization of a dihydroxo-bridged Pu moiety is discussed in terms of its relevance to the underlying mechanisms of tetravalent-metal-ion condensation« less

How mobile are dye adsorbates and acetonitrile molecules on the surface of TiO2 nanoparticles? A quasi-elastic neutron scattering study

PubMed Central

Vaissier, Valerie; Sakai, Victoria Garcia; Li, Xiaoe; Cabral, João T.; Nelson, Jenny; Barnes, Piers R. F.

2016-01-01

Motions of molecules adsorbed to surfaces may control the rate of charge transport within monolayers in systems such as dye sensitized solar cells. We used quasi-elastic neutron scattering (QENS) to evaluate the possible dynamics of two small dye moieties, isonicotinic acid (INA) and bis-isonicotinic acid (BINA), attached to TiO2 nanoparticles via carboxylate groups. The scattering data indicate that moieties are immobile and do not rotate around the anchoring groups on timescales between around 10 ps and a few ns (corresponding to the instrumental range). This gives an upper limit for the rate at which conformational fluctuations can assist charge transport between anchored molecules. Our observations suggest that if the conformation of larger dye molecules varies with time, it does so on longer timescales and/or in parts of the molecule which are not directly connected to the anchoring group. The QENS measurements also indicate that several layers of acetonitrile solvent molecules are immobilized at the interface with the TiO2 on the measurement time scale, in reasonable agreement with recent classical molecular dynamics results. PMID:27991538

Components of a standardised olive leaf dry extract (Ph. Eur.) promote hypothiocyanite production by lactoperoxidase.

PubMed

Flemmig, Jörg; Rusch, Dorothea; Czerwińska, Monika Ewa; Rauwald, Hans-Wilhelm; Arnhold, Jürgen

2014-05-01

We investigated in vitro the ability of a standardised olive leaf dry extract (Ph. Eur.) (OLE) as well as of its single components to circumvent the hydrogen peroxide-induced inhibition of the hypothiocyanite-producing activity of lactoperoxidase (LPO). The rate of hypothiocyanite (⁻OSCN) formation by LPO was quantified by spectrophotometric detection of the oxidation of 5-thio-2-nitrobenzoic acid (TNB). By using excess hydrogen peroxide, we forced the accumulation of inactive enzymatic intermediates which are unable to promote the two-electronic oxidation of thiocyanate. Both OLE and certain extract components showed a strong LPO-reactivating effect. Thereby an o-hydroxyphenolic moiety emerged to be essential for a good reactivity with the inactive LPO redox states. This basic moiety is found in the main OLE components oleuropein, oleacein, hydroxytyrosol, caffeic acid as well as in different other constituents including the OLE flavone luteolin. As LPO is a key player in the humoral immune response, these results propose a new mode of action regarding the well-known bacteriostatic and anti-inflammatory properties of the leaf extract of Olea europaea L. Copyright © 2014 Elsevier Inc. All rights reserved.

Pyridyl-Amides as a Multimode Self-Assembly Driver for the Design of a Stimuli-Responsive π-Gelator.

PubMed

Kartha, Kalathil K; Praveen, Vakayil K; Babu, Sukumaran Santhosh; Cherumukkil, Sandeep; Ajayaghosh, Ayyappanpillai

2015-10-01

An oligo(p-phenylenevinylene) (OPV) derivative connected to pyridyl end groups through an amide linkage (OPV-Py) resulted in a multistimuli-responsive π-gelator. When compared to the corresponding OPV π-gelator terminated by a phenyl-amide (OPV-Ph), the aggregation properties of OPV-Py were found to be significantly different, leading to multistimuli gelation and other morphological properties. The pyridyl moiety in OPV-Py initially interferes with the amide H-bonded assembly and gelation, however, protonation of the pyridyl moiety with trifluoroacetic acid (TFA) facilitated the formation of amide H-bonded assembly leading to gelation, which is reversible by the addition of N,N-diisopropyethylamine (DiPEA). Interestingly, addition of Ag(+) ions to a solution of OPV-Py facilitated the formation of a metallo-supramolecular assembly leading to gelation. Surprisingly, ultrasound-induced gelation was observed when OPV-Py was mixed with a dicarboxylic acid (A1). A detailed study using different spectroscopic and microscopic experimental techniques revealed the difference in the mode of assembly in the two molecules and the multistimuli-responsive nature of the OPV-Py gelation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structures and physiological roles of 13 integral lipids of bovine heart cytochrome c oxidase

PubMed Central

Shinzawa-Itoh, Kyoko; Aoyama, Hiroshi; Muramoto, Kazumasa; Terada, Hirohito; Kurauchi, Tsuyoshi; Tadehara, Yoshiki; Yamasaki, Akiko; Sugimura, Takashi; Kurono, Sadamu; Tsujimoto, Kazuo; Mizushima, Tsunehiro; Yamashita, Eiki; Tsukihara, Tomitake; Yoshikawa, Shinya

2007-01-01

All 13 lipids, including two cardiolipins, one phosphatidylcholine, three phosphatidylethanolamines, four phosphatidylglycerols and three triglycerides, were identified in a crystalline bovine heart cytochrome c oxidase (CcO) preparation. The chain lengths and unsaturated bond positions of the fatty acid moieties determined by mass spectrometry suggest that each lipid head group identifies its specific binding site within CcOs. The X-ray structure demonstrates that the flexibility of the fatty acid tails facilitates their effective space-filling functions and that the four phospholipids stabilize the CcO dimer. Binding of dicyclohexylcarbodiimide to the O2 transfer pathway of CcO causes two palmitate tails of phosphatidylglycerols to block the pathway, suggesting that the palmitates control the O2 transfer process.The phosphatidylglycerol with vaccenate (cis-Δ11-octadecenoate) was found in CcOs of bovine and Paracoccus denitrificans, the ancestor of mitochondrion, indicating that the vaccenate is conserved in bovine CcO in spite of the abundance of oleate (cis-Δ9-octadecenoate). The X-ray structure indicates that the protein moiety selects cis-vaccenate near the O2 transfer pathway against trans-vaccenate. These results suggest that vaccenate plays a critical role in the O2 transfer mechanism. PMID:17332748

Synthesis, spectroscopic characterization, biological screenings, DNA binding study and POM analyses of transition metal carboxylates.

PubMed

Uddin, Noor; Sirajuddin, Muhammad; Uddin, Nizam; Tariq, Muhammad; Ullah, Hameed; Ali, Saqib; Tirmizi, Syed Ahmed; Khan, Abdur Rehman

2015-04-05

This article contains the synthesis of a novel carboxylic acid derivative, its transition metal complexes and evaluation of biological applications. Six carboxylate complexes of transition metals, Zn(II) and Hg(II), have been successfully synthesized and characterized by FT-IR and NMR (1H, 13C). The ligand, HL, (4-[(2,6-Diethylphenyl)amino]-4-oxobutanoic acid) was also characterized by single crystal X-ray analysis. The complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date show the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than that of the free ligand. The ligand and its complexes were screened for antifungal and antileishmanial activities. The results showed that the ligand and its complexes are active with few exceptions. UV-visible spectroscopy and viscometry results reveal that the ligand and its complexes interact with the DNA via intercalative mode of interaction. A new and efficient strategy to identify the pharmacophores and anti-pharmacophores sites in carboxylate derivatives for the antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthesis, spectroscopic characterization, biological screenings, DNA binding study and POM analyses of transition metal carboxylates

NASA Astrophysics Data System (ADS)

Uddin, Noor; Sirajuddin, Muhammad; Uddin, Nizam; Tariq, Muhammad; Ullah, Hameed; Ali, Saqib; Tirmizi, Syed Ahmed; Khan, Abdur Rehman

2015-04-01

This article contains the synthesis of a novel carboxylic acid derivative, its transition metal complexes and evaluation of biological applications. Six carboxylate complexes of transition metals, Zn(II) and Hg(II), have been successfully synthesized and characterized by FT-IR and NMR (1H, 13C). The ligand, HL, (4-[(2,6-Diethylphenyl)amino]-4-oxobutanoic acid) was also characterized by single crystal X-ray analysis. The complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date show the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than that of the free ligand. The ligand and its complexes were screened for antifungal and antileishmanial activities. The results showed that the ligand and its complexes are active with few exceptions. UV-visible spectroscopy and viscometry results reveal that the ligand and its complexes interact with the DNA via intercalative mode of interaction. A new and efficient strategy to identify the pharmacophores and anti-pharmacophores sites in carboxylate derivatives for the antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.

Design of a new bottom antireflective coating composition for KrF resist

NASA Astrophysics Data System (ADS)

Mizutani, Kazuyoshi; Momota, Makoto; Aoai, Toshiaki; Yagihara, Morio

1999-06-01

A study for a new organic bottom antireflective coating (BARC) composition is described. A structural design of a light-absorbing dye was most important because dye structure not only plays a role in eliminating reflection from a substrate but also shows influence on dry etch rate of BARC material to a considerable extent. For example, an anthracene moiety with large absorption at 248 nm had undesirable dry etch resistance. 3-Hydroxy-2-naphthoic acid moiety was found to be one of suitable dyes for KrF BARC compositions, and the polymer bearing the dye showed enough absorbance and good erodability in dry etch. The BARC polymer was eroded as one and a half times faster than a novolak resin, and a little faster than an anthracene incorporated polymer. The result was discussed from the concepts of Ohnishi parameter and the ring parameter for dry etch durability of resist materials. BARC polymer should be thermoset by hard bake to eliminate intermixing with resist compositions. The BARC polymer bearing hydroxy group which is useful for a crosslinking reaction was thermoset in the presence of melamine-formaldehyde crosslinker and an acid catalyst after baking over 200 degrees C.

How mobile are dye adsorbates and acetonitrile molecules on the surface of TiO2 nanoparticles? A quasi-elastic neutron scattering study

NASA Astrophysics Data System (ADS)

Vaissier, Valerie; Sakai, Victoria Garcia; Li, Xiaoe; Cabral, João T.; Nelson, Jenny; Barnes, Piers R. F.

2016-12-01

Motions of molecules adsorbed to surfaces may control the rate of charge transport within monolayers in systems such as dye sensitized solar cells. We used quasi-elastic neutron scattering (QENS) to evaluate the possible dynamics of two small dye moieties, isonicotinic acid (INA) and bis-isonicotinic acid (BINA), attached to TiO2 nanoparticles via carboxylate groups. The scattering data indicate that moieties are immobile and do not rotate around the anchoring groups on timescales between around 10 ps and a few ns (corresponding to the instrumental range). This gives an upper limit for the rate at which conformational fluctuations can assist charge transport between anchored molecules. Our observations suggest that if the conformation of larger dye molecules varies with time, it does so on longer timescales and/or in parts of the molecule which are not directly connected to the anchoring group. The QENS measurements also indicate that several layers of acetonitrile solvent molecules are immobilized at the interface with the TiO2 on the measurement time scale, in reasonable agreement with recent classical molecular dynamics results.

Platinum(II)-dendrimer conjugates: synthesis and investigations on cytotoxicity, cellular distribution, platinum release, DNA, and protein binding.

PubMed

Kapp, Timo; Dullin, Anja; Gust, Ronald

2010-02-17

A set of polyamidoamine dendrimers were modified in such a way that they are able to act as carrier and drug delivery systems for cytostatics. The terminal binding of the non-proteinogenic D,L-2,3-diaminopropionic acid allowed the attachment of the cytotoxic PtX(2) moiety (X = Cl, I: A(PtI(2))(2), A(PtCl(2))(2), B(PtI(2))(2), B(PtCl(2))(2)), while the 2-carboxypentanedioic acid acted as leaving group for [meso-1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) ((m-4F-Pt)(3)C, (m-4F-Pt)(3)D). Poly(ethylene glycol) chains at C(PtI(2))(3) and C(PtCl(2))(3) as well as (m-4F-Pt)(3)C and (m-4F-Pt)(3)D mediated sufficient water solubility. Additional dansyl residues (B(PtI(2))(2) and (m-4F-Pt)(3)D) made a simultaneous determination of platinum (graphite furnace atomic absorption spectroscopy (GF-AAS)) and dendrimer (fluorimetry) possible. The ethylenediamine-terminated dendrimers were typically accumulated into MCF-7 cells in clathrin-dependent pathways and targeted the platinum moieties to the nuclear compartment. The highest intracellular platinum concentration and DNA binding caused the dendrimers A(PtX(2))(2) and B(PtX(2))(2). A coordinative DNA binding, however, is very unlikely because of low cytotoxic effects. (m-4F-Pt)(3)C and (m-4F-Pt)(3)D are labile conjugates and liberated the m-4F-Pt moiety in biological systems. The effects of these dendrimers were similar to that of the reference compounds m-4F-PtCl(2) and m-4F-Pt(H(2)O)(2).

Synthesis and characterization of thermally stable and/or conductive polymers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gajiwala, H.M.

1992-01-01

Eight new thermally stable polyimides were synthesized from two tricyclic heterocyclic diamines: thionine which has a phenothiazine moiety and proflavine which has an acridine unit. The polymerization reactions were optimized with respect to solvents, reaction time, reaction temperature, solid contents, etc., and their structure property relationships were studied. All these soluble polyimides have nice film forming properties. One of the polyimides containing the acridine moiety, appears to have a tendency to form a liquid crystalline state when its solution is passed through a fine capillary. All of these polyimides were thermally stable in air up to 500-550[degrees]C and up tomore » 600[degrees]C in a nitrogen atmosphere. They have refractive indices in the range of 1.65 to 1.85 and have relatively low value of permittivity. Two other thermally stable polymers, viz., polybenzimidazole and the ladder polymer having the phenazine moiety in the backbone were also synthesized. For these polymerization reactions, tetraamino derivative of phenazine was synthesized from the commercially available diamino, dinitro derivative of benzene. The polybenzimidazole was prepared via the azomethine pathway. This polymer had an intrinsic viscosity of 0.94 in methanesulfonic acid. The nice film forming polybenzimidazole polymer was found to be thermally stable up to 400[degrees]C. The ladder type of a polymer was synthesized by condensation polymerization between tetraaminophenazine and dihydroxybenzophenone in polyphosphoric acid at an elevated temperature. The completely conjugated ladder polymer was found to be semiconducting on doping with iodine. This polymer was highly crystalline as demonstrated by its X-ray diffraction pattern. A morphology study of the polymer indicated that the material has a tendency to form dendritic crystals. The polymer was thermally stable up to about 400[degrees]C in air.« less

Hydrogen bonds in betaine-acid (1:1) crystals revealed by Raman and 13C chemical shift tensors

NASA Astrophysics Data System (ADS)

Ilczyszyn, Marek; Ilczyszyn, Maria M.

2017-06-01

H-bonds of five betaine-acid (1:1) crystals are considered by analysis of tensors based on the Raman scissoring mode and 13C chemical shift of the betaine -CO1O2- carboxylate group. The leading structural factor in these systems is the strongest H-bond linking the betaine and the acidic moieties, (O1⋯H-O)com. The Raman and NMR tensors are strongly related to its character and to the R(O1⋯O)com distance. Very high molecular polarizability variation due to the scissoring vibration was found for the betaine-selenious acid crystal. The probable reason is modest network of H-bonds in this case and relatively high proton polarizability of these bonds.

Formation and Characterization of Self-Assembled Phenylboronic Acid Derivative Monolayers toward Developing Monosaccharide Sensing-Interface

PubMed Central

Chen, Hongxia; Lee, Minsu; Lee, Jaebeom; Kim, Jae-Ho; Gal, Yeong-Soon; Hwang, Yoon-Hwae; An, Won Gun; Koh, Kwangnak

2007-01-01

We designed and synthesized phenylboronic acid as a molecular recognition model system for saccharide detection. The phenylboronic acid derivatives that have boronic acid moiety are well known to interact with saccharides in aqueous solution; thus, they can be applied to a functional interface of saccharide sensing through the formation of self-assembled monolayer (SAM). In this study, self-assembled phenylboronic acid derivative monolayers were formed on Au surface and carefully characterized by atomic force microscopy (AFM), Fourier transform infrared reflection absorption spectroscopy (FTIR-RAS), surface enhanced Raman spectroscopy (SERS), and surface electrochemical measurements. The saccharide sensing application was investigated using surface plasmon resonance (SPR) spectroscopy. The phenylboronic acid monolayers showed good sensitivity of monosaccharide sensing even at the low concentration range (1.0 × 10−12 M). The SPR angle shift derived from interaction between phenylboronic acid and monosaccharide was increased with increasing the alkyl spacer length of synthesized phenylboronic acid derivatives.

Interaction of aromatic alcohols, aldehydes and acids with α-hydroxyl-containing carbon-centered radicals: A steady state radiolysis study

NASA Astrophysics Data System (ADS)

Samovich, S. N.; Brinkevich, S. D.; Shadyro, O. I.

2013-01-01

Benzaldehyde and its derivatives efficaciously oxidize in aqueous solutions α-hydroxyl-containing carbon-centered radicals (α-HCR) of various structures, suppressing thereby the radical recombination and fragmentation reactions. The compounds containing cinnamic moieties are capable of adding α-hydroxyethyl radicals (α-HER) to the carbon-carbon double bonds conjugated with the aromatic system to form molecular products identifiable by mass spectrometry. On radiolysis of aqueous ethanol solutions, reduction of α-HER by aromatic alcohols and acids has been shown to proceed via formation of their adducts with hydrated electron species.

The Role of the Acidity of N-Heteroaryl Sulfonamides as Inhibitors of Bcl-2 Family Protein–Protein Interactions

PubMed Central

2013-01-01

Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263. PMID:24900652

[Synthetic transformations of higher terpenoids. XXX. Synthesis and cytotoxic activity of betulonic acid amides with a piperidine or pyrrolidine nitroxide moiety].

PubMed

Antimonova, A N; Petrenko, N I; Shults, E E; Polienko, Iu F; Shakirov, M M; Irtegova, I G; Pokrovskiĭ, M A; Sherman, K M; Grigor'ev, I A; Pokrovskiĭ, A G; Tolstikov, G A

2013-01-01

The reaction of betulonic acid chloride with 4-amino-2,2,6,6-tetramethylpeperidine-1-oxyl, 3-amino-2,2,5,5-tetramethylpyrrolidine-1-oxyl and 3-aminomethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl gave corresponding triterpenoid amides. It was found that new derivatives exhibit cytotoxic activity against tumor cells CEM-13, U-937, MT-4. CCID50 value for most activity compound--N-[3-oxolup-20(29)-en-30-yl]-(2,2,6,6-tetramethylpiperidine-4-yl)-1-oxyl--was 5.7-33.1 microM.

Coloration of tyrosine by organic-semiconductor interfacial charge-transfer transitions

NASA Astrophysics Data System (ADS)

Fujisawa, Jun-ichi; Kikuchi, Natsumi; Hanaya, Minoru

2016-11-01

L-tyrosine (Tyr) plays a crucial role as a proteinogenic amino acid and also as a precursor to several neurotransmitters and hormones. Here we demonstrate coloration of Tyr based on organic-semiconductor interfacial charge-transfer (ICT) transitions. The ICT transitions from Tyr to TiO2 are induced by the chemisorption of Tyr on TiO2 surfaces via the hydroxy group of the phenol moiety. Because other amino acids possess no chemical group to induce ICT transitions, this coloration method enables to detect Tyr selectively without drastic structural change in contrast to the conventional coloration methods.

An Experimental and Kinetic Modeling Study of Methyl Decanoate Combustion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarathy, S M; Thomson, M J; Pitz, W J

2009-12-04

Biodiesel is a mixture of long chain fatty acid methyl esters derived from fats and oils. This research study presents opposed-flow diffusion flame data for one large fatty acid methyl ester, methyl decanoate, and uses the experiments to validate an improved skeletal mechanism consisting of 648 species and 2998 reactions. The results indicate that methyl decanoate is consumed via abstraction of hydrogen atoms to produce fuel radicals, which lead to the production of alkenes. The ester moiety in methyl decanoate leads to the formation of low molecular weight oxygenated compounds such as carbon monoxide, formaldehyde, and ketene.

Alkyl piperidine and piperazine hydroxamic acids as HDAC inhibitors.

PubMed

Rossi, Cristina; Porcelloni, Marina; D'Andrea, Piero; Fincham, Christopher I; Ettorre, Alessandro; Mauro, Sandro; Squarcia, Antonella; Bigioni, Mario; Parlani, Massimo; Nardelli, Federica; Binaschi, Monica; Maggi, Carlo A; Fattori, Daniela

2011-04-15

We report here the strategy used in our research group to find a new class of histone deacetylase (HDAC) inhibitors. A series of N-substituted 4-alkylpiperazine and 4-alkylpiperidine hydroxamic acids, corresponding to the basic structure of HDAC inhibitors (zinc binding moiety-linker-capping group) has been designed, prepared, and tested for HDAC inhibition. Linker length and aromatic capping group connection were systematically varied to find the optimal geometric parameters. A new series of submicromolar inhibitors was thus identified, which showed antiproliferative activity on HCT-116 colon carcinoma cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

A benzothiazole-based fluorescent probe for hypochlorous acid detection and imaging in living cells

NASA Astrophysics Data System (ADS)

Nguyen, Khac Hong; Hao, Yuanqiang; Zeng, Ke; Fan, Shengnan; Li, Fen; Yuan, Suke; Ding, Xuejing; Xu, Maotian; Liu, You-Nian

2018-06-01

A benzothiazole-based turn-on fluorescent probe with a large Stokes shift (190 nm) has been developed for hypochlorous acid detection. The probe displays prompt fluorescence response for HClO with excellent selectivity over other reactive oxygen species as well as a low detection limit of 0.08 μM. The sensing mechanism involves the HClO-induced specific oxidation of oxime moiety of the probe to nitrile oxide, which was confirmed by HPLC-MS technique. Furthermore, imaging studies demonstrated that the probe is cell permeable and can be applied to detect HClO in living cells.

Brönsted Acid-Catalyzed One-Pot Synthesis of Indoles from o-Aminobenzyl Alcohols and Furans

PubMed Central

Kuznetsov, Alexey; Makarov, Anton; Rubtsov, Alexandr E.; Butin, Alexander V.; Gevorgyan, Vladimir

2013-01-01

Brönsted acid-catalyzed one-pot synthesis of indoles from o-aminobenzyl alcohols and furans has been developed. This method operates via the in situ formation of aminobenzylfuran, followed by its recyclization into the indole core. The method proved to be efficient for substrates possessing different functional groups, including -OMe, -CO2Cy, and -Br. The resulting indoles can easily be transformed into diverse scaffolds, including 2,3- and 1,2-fused indoles, and indole possessing an α,β-unsaturated ketone moiety at the C-2 position. PMID:24255969

Site-selective chemical modification of chymotrypsin using peptidyl derivatives bearing optically active diphenyl 1-amino-2-phenylethylphosphonate: Stereochemical effect of the diphenyl phosphonate moiety.

PubMed

Ono, Shin; Nakai, Takahiko; Kuroda, Hirofumi; Miyatake, Ryuta; Horino, Yoshikazu; Abe, Hitoshi; Umezaki, Masahito; Oyama, Hiroshi

2016-11-04

Diphenyl (α-aminoalkyl)phosphonates act as mechanism-based inhibitors against serine proteases by forming a covalent bond with the hydroxy group of the active center Ser residue. Because the covalent bond was found to be broken and replaced by 2-pyridinaldoxime methiodide (2PAM), we employed a peptidyl derivative bearing diphenyl 1-amino-2-phenylethylphosphonate moiety (Phe(p) (OPh)2 ) to target the active site of chymotrypsin and to selectively anchor to Lys175 in the vicinity of the active site. Previously, it was reported that the configuration of the α-carbon of phosphorus in diphenyl (α-aminoalkyl)phosphonates affects the inactivation reaction of serine proteases, i.e., the (R)-enantiomeric diphenyl phosphonate is comparable to l-amino acids and it effectively reacts with serine proteases, whereas the (S)-enantiomeric form does not. In this study, we evaluated the stereochemical effect of the phosphonate moiety on the selective chemical modification. Epimeric dipeptidyl derivatives, Ala-(R or S)-Phe(p) (OPh)2 , were prepared by separation with RP-HPLC. A tripeptidyl (R)-epimer (Ala-Ala-(R)-Phe(p) (OPh)2 ) exhibited a more potent inactivation ability against chymotrypsin than the (S)-epimer. The enzyme inactivated by the (R)-epimer was more effectively reactivated with 2PAM than the enzyme inactivated by the (S)-epimer. Finally, N-succinimidyl (NHS) active ester derivatives, NHS-Suc-Ala-Ala- (R or S)-Phe(p) (OPh)2 , were prepared, and we evaluated their action when modifying Lys175 in chymotrypsin. We demonstrated that the epimeric NHS derivative that possessed the diphenyl phosphonate moiety with the (R)-configuration effectively modified Lys175 in chymotrypsin, whereas that with the (S)-configuration did not. These results demonstrate the utility of peptidyl derivatives that bear an optically active diphenyl phosphonate moiety as affinity labeling probes in protein bioconjugation. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 521-530, 2016. © 2015 Wiley Periodicals, Inc.

Boron-dipyrromethene based reversible and reusable selective chemosensor for fluoride detection.

PubMed

Madhu, Sheri; Ravikanth, Mangalampalli

2014-02-03

We synthesized benzimidazole substituted boron-dipyrromethene 1 (BODIPY 1) by treating 3,5-diformyl BODIPY 2 with o-phenylenediamine under mild acid catalyzed conditions and characterized by using various spectroscopic techniques. The X-ray structure analysis revealed that the benzimidazole NH group is involved in intramolecular hydrogen bonding with fluoride atoms which resulted in a coplanar geometry between BODIPY and benzimidazole moiety. The presence of benzimidazole moiety at 3-position of BODIPY siginificantly altered the electronic properties, which is clearly evident in bathochromic shifts of absorption and fluorescence bands, improved quantum yields, increased lifetimes compared to BODIPY 2. The anion binding studies indicated that BODIPY 1 showed remarkable selectivity and specificity toward F(-) ion over other anions. Addition of F(-) ion to BODIPY 1 resulted in quenching of fluorescence accompanied by a visual detectable color change from fluorescent pink to nonfluorescent blue. The recognition mechanism is attributed to a fluoride-triggered disruption of the hydrogen bonding between BODIPY and benzimidazole moieties leading to (i) noncoplanar geometry between BODIPY and benzimidazole units and (ii) operation of photoinduced electron transfer (PET) from benzimidazole moiety to BODIPY unit causing quenching of fluorescence. Interestingly, when we titrated the nonfluorescent blue 1-F(-) solution with TFA resulted in a significant enhancement of fluorescence intensity (15-fold) because the PET quenching is prevented due to protonation of benzimidazole group. Furthermore, the reversibility and reusability of sensor 1 for the detection of F(-) ion was tested for six cycles indicating the sensor 1 is stable and can be used in reversible manner.

Biotin and Lipoic Acid: Synthesis, Attachment and Regulation

PubMed Central

Cronan, John E.

2014-01-01

Summary Two vitamins, biotin and lipoic acid, are essential in all three domains of life. Both coenzymes function only when covalently attached to key metabolic enzymes. There they act as “swinging arms” that shuttle intermediates between two active sites (= covalent substrate channeling) of key metabolic enzymes. Although biotin was discovered over 100 years ago and lipoic acid 60 years ago, it was not known how either coenzyme is made until recently. In Escherichia coli the synthetic pathways for both coenzymes have now been worked out for the first time. The late steps of biotin synthesis, those involved in assembling the fused rings, were well-described biochemically years ago, although recent progress has been made on the BioB reaction, the last step of the pathway in which the biotin sulfur moiety is inserted. In contrast, the early steps of biotin synthesis, assembly of the fatty acid-like “arm” of biotin were unknown. It has now been demonstrated that the arm is made by using disguised substrates to gain entry into the fatty acid synthesis pathway followed by removal of the disguise when the proper chain length is attained. The BioC methyltransferase is responsible for introducing the disguise and the BioH esterase for its removal. In contrast to biotin, which is attached to its cognate proteins as a finished molecule, lipoic acid is assembled on its cognate proteins. An octanoyl moiety is transferred from the octanoyl-ACP of fatty acid synthesis to a specific lysine residue of a cognate protein by the LipB octanoyl transferase followed by sulfur insertion at carbons C6 and C8 by the LipA lipoyl synthetase. Assembly on the cognate proteins regulates the amount of lipoic acid synthesized and thus there is no transcriptional control of the synthetic genes. In contrast transcriptional control of the biotin synthetic genes is wielded by a remarkably sophisticated, yet simple, system, exerted through BirA a dual function protein that both represses biotin operon transcription and ligates biotin to its cognate protein. PMID:26442940

Megalin-Mediated Oligonucleotide Trafficking for Breast Cancer Chemosensitization

DTIC Science & Technology

2010-08-01

role of apoprotein J (clusterin) in atherogenesis: binding to enzymatically modified low- density lipoprotein reduces fatty acid-mediated cytotoxicity...therapeutics trafficking [1]. High megalin expression may reflect the level of chemoresistance of the cancer cells [2], while clusterin is known to cause...targeting moieties such as apolipoprotein E (Apo-E) [5] will enhance siRNA delivery into breast cancer cells which reportedly express high megalin level

Theoretical Study of Electron Transfer Properties of Squaraine Dyes for Dye Sensitized Solar Cell

NASA Astrophysics Data System (ADS)

Juwita, Ratna; Tsai, Hui-Hsu Gavin

2018-01-01

The environmental issues and high cost of Ru create many scientists to explore cheaper and safer sensitizer as alternative for dye sensitized solar cells (DSCs). Dyes play an important role in solar energy conversion efficiency. The squaraine (SQ) dyes has good spectral match with the solar spectra, therefore, SQ dyes have great potential for the applications in DSCs. SQ01_CA is an unsymmetrical SQ dye, reported by Grätzel and colleagues in 2007, featuring a D-π-spacer-A framework and has a carboxylic acid anchoring group. The electron donating ability of indolium in SQ01_CA and SQ01_CAA dyes is relatively weak, better performance may be achieved by introducing an additional donor moiety into indolium [1]. In this study, we investigate six unsymmetrical SQ dyes adsorbed on a (TiO2)38 cluster [2] using density functional theory (DFT) and time-dependent DFT to study electron transfer properties of squaraine dyes on their photophysical. SQ01_CA, WH-SQ01_CA, and WH-SQ02_CA use a carboxylic acid group as its electron acceptor. Furthermore, SQ01_CAA, WH-SQ01_CAA, and WH-SQ02_CAA use a cyanoacrylic acid group as its electron acceptor. WH-SQ01_CA and WH-SQ01_CAA have an alkyl, while WH-SQ02_CA and WH-SQ02_CAA have alkoxyl substituted diarylamines to the indolium donor of sensitizer SQ01_CA. Our calculations show with additional diarylamines in donor tail of WH-SQ02_CAA, the SQ dyes have red-shifted absorption and have slightly larger probability of electron density transferred to TiO2 moiety. Furthermore, an additional -CN group as electron a withdrawing group in the acceptor exhibits red-shifted absorption and enhances the electron density transferred to TiO2 and anchoring moiety after photo-excitation. The tendency of calculated probabilities of electron density being delocalized into TiO2 and driving force for excited-state electron injection of these studied SQ dyes is compatible with their experimentally observed.

Intelligent nanomedicine integrating diagnosis and therapy

NASA Technical Reports Server (NTRS)

Li, Na (Inventor); Tan, Winny (Inventor)

2012-01-01

A method of controlling the activity of a biologically active compound. The method concerns an oligonucleotide-based compound, comprising a hairpin-forming oligonucleotide, an effector moiety physically associated with the oligonucleotide, where the effector moiety possesses a biological activity, and a regulating moiety physically associated with the oligonucleotide, where the regulating moiety controls the biological activity of the effector moiety by interacting with the effector moiety. The oligonucleotide can assume a hairpin configuration, where the effector and regulating moieties interact, or an open configuration, where the effector and regulating moieties fail to interact. Depending on the nature of the effector and regulating moieties, either configuration can result in the expression of the biological activity of the effector moiety.

Photo-crosslinked hyaluronic acid coated upconverting nanoparticles

NASA Astrophysics Data System (ADS)

Mrazek, Jiri; Kettou, Sofiane; Matuska, Vit; Svozil, Vit; Huerta-Angeles, Gloria; Pospisilova, Martina; Nesporova, Kristina; Velebny, Vladimir

2017-02-01

Hyaluronic acid (HA)-coated inorganic nanoparticles display enhanced interaction with the CD44 receptors which are overexpressed in many types of cancer cells. Here, we describe a modification of core-shell β-NaY0.80Yb0.18Er0.02F4@NaYF4 nanoparticles (UCNP) by HA derivative bearing photo-reactive groups. UCNP capped with oleic acid were firstly transferred to aqueous phase by an improved protocol using hydrochloric acid or lactic acid treatment. Subsequently, HA bearing furanacryloyl moieties (HA-FU) was adsorbed on the nanoparticle surface and crosslinked by UV irradiation. The crosslinking resulted in stable HA coating, and no polymer desorption was observed. As-prepared UCNP@HA-FU show a hydrodynamic diameter of about 180 nm and are colloidally stable in water and cell culture media. The cellular uptake by normal human fibroblasts and MDA MB-231 cancer cell line was investigated by upconversion luminescence imaging.

Lipoic acid and dihydrolipoic acid. A comprehensive theoretical study of their antioxidant activity supported by available experimental kinetic data.

PubMed

Castañeda-Arriaga, Romina; Alvarez-Idaboy, J Raul

2014-06-23

The free radical scavenging activity of lipoic acid (LA) and dihydrolipoic acid (DHLA) has been studied in nonpolar and aqueous solutions, using the density functional theory and several oxygen centered radicals. It was found that lipoic acid is capable of scavenging only very reactive radicals, while the dehydrogenated form is an excellent scavenger via a hydrogen transfer mechanism. The environment plays an important role in the free radical scavenging activity of DHLA because in water it is deprotonated, and this enhances its activity. In particular, the reaction rate constant of DHLA in water with an HOO(•) radical is close to the diffusion limit. This has been explained on the basis of the strong H-bonding interactions found in the transition state, which involve the carboxylate moiety, and it might have implications for other biological systems in which this group is present.

Peptides whose uptake by cells is controllable

DOEpatents

Jiang, Tao [San Diego, CA; Tsien, Roger Y [La Jolla, CA

2012-02-07

A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.

Peptides whose uptake by cells is controllable

DOEpatents

Jiang, Tao [San Diego, CA; Tsien, Roger Y [La Jolla, CA

2008-10-07

A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.

Peptides whose uptake by cells is controllable

DOEpatents

Jiang, Tao; Tsien, Roger Y

2014-02-04

A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.

Synthesis and characterization of bifunctional surfaces with tunable functional group pairs

NASA Astrophysics Data System (ADS)

Galloway, John M.; Kung, Mayfair; Kung, Harold H.

2016-06-01

Grafting of pairs of functional groups onto a silica surface was demonstrated by tethering both terminals of an organochlorosilane precursor molecule, Cl2(CH3)Si(CH2)4(CO)(OSi(i-Pr)2)(CH2)2Si(CH3)Cl2, that possess a cleavable silyl ester bond, onto a silica surface. Hydrolytic cleavage of the silyl ester bond of the grafted molecule resulted in the generation of organized pairs of carboxylic acid and organosilanol groups. This organosilanol moiety was easily transformed into other functional groups through condensation reactions to form, together with the neighboring acid group, pairs such as carboxylic acid/secondary amine, carboxylic acid/pyridine, and carboxylic acid/phosphine. In the case of carboxylic acid/amine pairing, there was evidence of the formation of amide. A sample grafted with amine-carboxylic acid pairs was three times more active (per free amine) than a sample without such pairs for the nitroaldol condensation of 4-nitrobenzaldehyde and nitromethane.

High concentrations of furan fatty acids in organic butter samples from the German market.

PubMed

Wendlinger, Christine; Vetter, Walter

2014-08-27

Furan fatty acids (F-acids) are valuable antioxidants containing a furan moiety in the central part of the molecule. They occur in the lipids of different foodstuffs and plants, with grass being the main source for their presence in milk fat and butter. Because cows from organic farming receive higher portions of grass-based feed, it was tested whether organic butter samples (n = 26) contain more F-acids than conventional ones (n = 25) in Germany. For this purpose, samples were melted, and the lipid phase was separated and transesterified into methyl esters, which were enriched using silver ion chromatography and analyzed by GC-EI/MS in the selected ion monitoring (SIM) mode. Levels of F-acids in butter were higher in summer than in winter, and in both seasons, organic samples contained significantly higher levels of F-acids than conventional ones (one-way ANOVA: p < 0.001). Furthermore, the daily intake of F-acids via milk fat and other foodstuffs was calculated.

ORIGIN OF PALMITIC ACID CARBON IN PALMITATES FORMED FROM HEXADECANE-1-C14 AND TETRADECANE-1-C14 BY MICROCOCCUS CERIFICANS

PubMed Central

Finnerty, W. R.; Kallio, R. E.

1964-01-01

Finnerty, W. R. (University of Iowa, Iowa City), and R. E. Kallio. Origin of palmitic acid carbon in palmitates formed from hexadecane-1-C14 and tetradecane-1-C14 by Micrococcus cerificans. J. Bacteriol. 87:1261–1265. 1964.—Degradation of the palmitic acid moiety of cetyl palmitate and myristyl palmitate formed from hexadecane-1-C14 and tetradecane-1-C14 by Micrococcus cerificans was carried out. The patterns of C14 labeling in palmitic acid from cetyl palmitate showed that hexadecane is oxidized at the C1 position, and cetyl alcohol and palmitic acid thus formed are directly esterified. Palmitic acid arising from tetradecane and esterified to tetradecanol appeared to have been synthesized by the addition of two carbon atoms to an existing 14-carbon atom skeleton. Considerable mixing of C14 occurred in the C1 and C2 positions of palmitic acid thus synthesized. PMID:14188700

Construction of energy transfer pathways self-assembled from DNA-templated stacks of anthracene.

PubMed

Iwaura, Rika; Yui, Hiroharu; Someya, Yuu; Ohnishi-Kameyama, Mayumi

2014-01-05

We describe optical properties of anthracene stacks formed from single-component self-assembly of thymidylic acid-appended anthracene 2,6-bis[5-(3'-thymidylic acid)pentyloxy] anthracene (TACT) and the binary self-assembly of TACT and complementary 20-meric oligoadenylic acid (TACT/dA20) in an aqueous buffer. UV-Vis and emission spectra for the single-component self-assembly of TACT and the binary self-assembly of TACT/dA20 were very consistent with stacked acene moieties in both self-assemblies. Interestingly, time-resolved fluorescence spectra from anthracene stacks exhibited very different features of the single-component and binary self-assemblies. In the single-component self-assembly of TACT, a dynamic Stokes shift (DSS) and relatively short fluorescence lifetime (τ=0.35ns) observed at around 450nm suggested that the anthracene moieties were flexible. Moreover, a broad emission at 530nm suggested the formation of an excited dimer (excimer). In the binary self-assembly of TACT/dA20, we detected a broad, red-shifted emission component at 534nm with a lifetime (τ=0.4ns) shorter than that observed in the TACT single-component self-assembly. Combining these results with the emission spectrum of the binary self-assembly of TACT/5'-HEX dA20, we concluded that the energy transfer pathway was constructed by columnar anthracene stacks formed from the DNA-templated self-assembly of TACT. Copyright © 2013 Elsevier B.V. All rights reserved.

Tetranuclear copper(II) complexes bridged by alpha-D-glucose-1-phosphate and incorporation of sugar acids through the Cu4 core structural changes.

PubMed

Kato, Merii; Sah, Ajay Kumar; Tanase, Tomoaki; Mikuriya, Masahiro

2006-08-21

Tetranuclear copper(II) complexes containing alpha-D-glucose-1-phosphate (alpha-D-Glc-1P), [Cu4(mu-OH){mu-(alpha-D-Glc-1P)}2(bpy)4(H2O)2]X3 [X = NO3 (1a), Cl (1b), Br (1c)], and [Cu4(mu-OH){mu-(alpha-D-Glc-1P)}2(phen)4(H2O)2](NO3)3 (2) were prepared by reacting the copper(II) salt with Na2[alpha-D-Glc-1P] in the presence of diimine ancillary ligands, and the structure of 2 was characterized by X-ray crystallography to comprise four {Cu(phen)}2+ fragments connected by the two sugar phosphate dianions in 1,3-O,O' and 1,1-O mu4-bridging fashion as well as a mu-hydroxo anion. The crystal structure of 2 involves two chemically independent complex cations in which the C2 enantiomeric structure for the trapezoidal tetracopper(II) framework is switched according to the orientation of the alpha-D-glucopyranosyl moieties. Temperature-dependent magnetic susceptibility data of 1a indicated that antiferromagnetic spin coupling is operative between the two metal ions joined by the hydroxo bridge (J = -52 cm(-1)) while antiferromagnetic interaction through the Cu-O-Cu sugar phosphate bridges is weak (J = -13 cm(-1)). Complex 1a readily reacted with carboxylic acids to afford the tetranuclear copper(II) complexes, [Cu4{mu-(alpha-D-Glc-1P)}2(mu-CA)2(bpy)4](NO3)2 [CA = CH3COO (3), o-C6H4(COO)(COOH) (4)]. Reactions with m-phenylenediacetic acid [m-C6H4(CH2COOH)2] also gave the discrete tetracopper(II) cationic complex [Cu4{mu-(alpha-D-Glc-1P)}2(mu-m-C6H4(CH2COO)(CH2COOH))2(bpy)4](NO3)2 (5a) as well as the cluster polymer formulated as {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-m-C6H4(CH2COO)2)(bpy)4](NO3)2}n (5b). The tetracopper structure of 1a is converted into a symmetrical rectangular core in complexes 3, 4, and 5b, where the hydroxo bridge is dissociated and, instead, two carboxylate anions bridge another pair of Cu(II) ions in a 1,1-O monodentate fashion. The similar reactions were applied to incorporate sugar acids onto the tetranuclear copper(II) centers. Reactions of 1a with delta-D-gluconolactone, D-glucuronic acid, or D-glucaric acid in dimethylformamide resulted in the formation of discrete tetracopper complexes with sugar acids, [Cu4{mu-(alpha-D-Glc-1P)}2(mu-SA)2(bpy)4](NO3)2 [SA = D-gluconate (6), D-glucuronate (7), D-glucarateH (8a)]. The structures of 6 and 7 were determined by X-ray crystallography to be almost identical with that of 3 with additional chelating coordination of the C-2 hydroxyl group of D-gluconate moieties (6) or the C-5 cyclic O atom of D-glucuronate units (7). Those with D-glucaric acid and D-lactobionic acid afforded chiral one-dimensional polymers, {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-D-glucarate)(bpy)4](NO3)2}n (8b) and {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-D-lactobionate)(bpy)4(H2O)2](NO3)3}n (9), respectively, in which the D-Glc-1P-bridged tetracopper(II) units are connected by sugar acid moieties through the C-1 and C-6 carboxylate O atoms in 8b and the C-1 carboxylate and C-6 alkoxy O atoms of the gluconate chain in 9. When complex 7 containing d-glucuronate moieties was heated in water, the mononuclear copper(II) complex with 2-dihydroxy malonate, [Cu(mu-O2CC(OH)2CO2)(bpy)] (10), and the dicopper(II) complex with oxalate, [Cu2(mu-C2O4)(bpy)2(H2O)2](NO3)2 (11), were obtained as a result of oxidative degradation of the carbohydrates through C-C bond cleavage reactions.

Fatty Acids in Membranes as Homeostatic, Metabolic and Nutritional Biomarkers: Recent Advancements in Analytics and Diagnostics.

PubMed

Ferreri, Carla; Masi, Annalisa; Sansone, Anna; Giacometti, Giorgia; Larocca, Anna Vita; Menounou, Georgia; Scanferlato, Roberta; Tortorella, Silvia; Rota, Domenico; Conti, Marco; Deplano, Simone; Louka, Maria; Maranini, Anna Rosaria; Salati, Arianna; Sunda, Valentina; Chatgilialoglu, Chryssostomos

2016-12-22

Fatty acids, as structural components of membranes and inflammation/anti-inflammatory mediators, have well-known protective and regulatory effects. They are studied as biomarkers of pathological conditions, as well as saturated and unsaturated hydrophobic moieties in membrane phospholipids that contribute to homeostasis and physiological functions. Lifestyle, nutrition, metabolism and stress-with an excess of radical and oxidative processes-cause fatty acid changes that are examined in the human body using blood lipids. Fatty acid-based membrane lipidomics represents a powerful diagnostic tool for assessing the quantity and quality of fatty acid constituents and also for the follow-up of the membrane fatty acid remodeling that is associated with different physiological and pathological conditions. This review focuses on fatty acid biomarkers with two examples of recent lipidomic research and health applications: (i) monounsaturated fatty acids and the analytical challenge offered by hexadecenoic fatty acids (C16:1); and (ii) the cohort of 10 fatty acids in phospholipids of red blood cell membranes and its connections to metabolic and nutritional status in healthy and diseased subjects.

Fatty Acids in Membranes as Homeostatic, Metabolic and Nutritional Biomarkers: Recent Advancements in Analytics and Diagnostics

PubMed Central

Ferreri, Carla; Masi, Annalisa; Sansone, Anna; Giacometti, Giorgia; Larocca, Anna Vita; Menounou, Georgia; Scanferlato, Roberta; Tortorella, Silvia; Rota, Domenico; Conti, Marco; Deplano, Simone; Louka, Maria; Maranini, Anna Rosaria; Salati, Arianna; Sunda, Valentina; Chatgilialoglu, Chryssostomos

2016-01-01

Fatty acids, as structural components of membranes and inflammation/anti-inflammatory mediators, have well-known protective and regulatory effects. They are studied as biomarkers of pathological conditions, as well as saturated and unsaturated hydrophobic moieties in membrane phospholipids that contribute to homeostasis and physiological functions. Lifestyle, nutrition, metabolism and stress—with an excess of radical and oxidative processes—cause fatty acid changes that are examined in the human body using blood lipids. Fatty acid-based membrane lipidomics represents a powerful diagnostic tool for assessing the quantity and quality of fatty acid constituents and also for the follow-up of the membrane fatty acid remodeling that is associated with different physiological and pathological conditions. This review focuses on fatty acid biomarkers with two examples of recent lipidomic research and health applications: (i) monounsaturated fatty acids and the analytical challenge offered by hexadecenoic fatty acids (C16:1); and (ii) the cohort of 10 fatty acids in phospholipids of red blood cell membranes and its connections to metabolic and nutritional status in healthy and diseased subjects. PMID:28025506

Genetic encoding of a bicyclo[6.1.0]nonyne-charged amino acid enables fast cellular protein imaging by metal-free ligation.

PubMed

Borrmann, Annika; Milles, Sigrid; Plass, Tilman; Dommerholt, Jan; Verkade, Jorge M M; Wiessler, Manfred; Schultz, Carsten; van Hest, Jan C M; van Delft, Floris L; Lemke, Edward A

2012-09-24

Visualizing biomolecules by fluorescent tagging is a powerful method for studying their behaviour and function inside cells. We prepared and genetically encoded an unnatural amino acid (UAA) that features a bicyclononyne moiety. This UAA offered exceptional reactivity in strain-promoted azide-alkyne cycloadditions. Kinetic measurements revealed that the UAA reacted also remarkably fast in the inverse-electron-demand Diels-Alder cycloaddition with tetrazine-conjugated dyes. Genetic encoding of the new UAA inside mammalian cells and its subsequent selective labeling at low dye concentrations demonstrate the usefulness of the new amino acid for future imaging studies. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and evaluation of triazole linked glycosylated 18β-glycyrrhetinic acid derivatives as anticancer agents.

PubMed

Parida, Pravat Kumar; Sau, Abhijit; Ghosh, Tamashree; Jana, Kuladip; Biswas, Kaushik; Raha, Sanghamitra; Misra, Anup Kumar

2014-08-15

A series of glycosyl triazol linked 18β-glycyrrhetinic acid (GA) derivatives have been synthesized using 1,3-dipolar cycloaddition reaction of per-O-acetylated glycosyl azide derivatives (4a-h) with propargyl ester of 18β-glycyrrhetinic acid (GA) (2 and 3) following the concept of 'Click chemistry'. The synthesized triazole derivatives were de-O-acetylated to furnish compounds (7a-h and 8a-c) with free hydroxyl groups in the carbohydrate moieties, which were evaluated for their anticancer potential against human cervical cancer cells (HeLa) and normal kidney epithelial (NKE) cells. GA (1), compound 7d, compound 7g and compound 8c showed promising anticancer activities. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pentasaccharide resin glycosides from Ipomoea pes-caprae.

PubMed

Yu, Bang-Wei; Luo, Jian-Guang; Wang, Jun-Song; Zhang, Dong-Ming; Yu, Shi-Shan; Kong, Ling-Yi

2011-04-25

Pescapreins XXI-XXX (1-10), pentasaccharide resin glycosides, together with the known pescapreins I-IV and stoloniferin III were isolated from the aerial parts of Ipomoea pes-caprae (beach morning-glory). The pescapreins are macrolactones of simonic acid B, partially esterified with different fatty acids. The lactonization site of the aglycone, jalapinolic acid, was located at C-2 or C-3 of the second saccharide moiety. Their structures were established by a combination of spectroscopic and chemical methods. Compounds 1-10 were evaluated for their potential to modulate multidrug resistance in the human breast cancer cell line MCF-7/ADR. The combined use of these new compounds at a concentration of 5 μg/mL increased the cytotoxicity of doxorubicin by 1.5-3.7-fold.

Raman mapping and in situ SERS spectroelectrochemical studies of 6-mercaptopurine SAMs on the gold electrode.

PubMed

Yang, Haifeng; Liu, Yanli; Liu, Zhimin; Yang, Yu; Jiang, Jianhui; Zhang, Zongrang; Shen, Guoli; Yu, Ruqin

2005-02-24

The self-assembled monolayers (SAMs) of 6-mercaptopurine (6MP) were formed at the roughened polycrystalline gold surfaces in acid and alkaline media. The time-dependent Raman mapping spectral analysis in conjunction with the quantum calculations for the vibrational modes using ab initio BLYP/6-31G method suggested that both of the resulted 6MP SAMs adopted the same adsorption mode through the S atom of pyrimidine moiety and the N7 atom of the imidazole moiety anchoring the gold surface in a vertical way. The in situ surface-enhanced Raman scattering spectroelectrochemical experiment was conducted to examine the stability of the SAMs at various bias potentials. It was found that the detaching process of the 6MP SAMs from the surface involved one electron reduction as the voltage was applied at ca. 0.7 V vs a standard calomel electrode.

Design, Synthesis, and Biological Evaluation of Novel 1,3,4-Thiadiazole Derivatives as Potential Antitumor Agents against Chronic Myelogenous Leukemia: Striking Effect of Nitrothiazole Moiety

DOE PAGES

Altıntop, Mehlika; Ciftci, Halil; Radwan, Mohamed; ...

2017-12-27

In an attempt to develop potent antitumor agents, new 1,3,4-thiadiazole derivatives were synthesized and evaluated for their cytotoxic effects on multiple human cancer cell lines, including the K562 chronic myelogenous leukemia cell line that expresses the Bcr-Abl tyrosine kinase. N-(5-Nitrothiazol-2-yl)-2-((5-((4-(trifluoromethyl)phenyl)amino)-1,3,4-thiadiazol-2-yl)thio)acetamide (2) inhibited the Abl protein kinase with an IC 50 value of 7.4 µM and showed selective activity against the Bcr-Abl positive K562 cell line. Furthermore, a Bcr-Abl-compound 2 molecular modelling simulation highlighted the anchoring role of the nitrothiazole moiety in bonding and hydrophobic interaction with the key amino acid residues. These results provide promising starting points for further developmentmore » of novel kinase inhibitors.« less

Design, Synthesis, and Biological Evaluation of Novel 1,3,4-Thiadiazole Derivatives as Potential Antitumor Agents against Chronic Myelogenous Leukemia: Striking Effect of Nitrothiazole Moiety

DOE Office of Scientific and Technical Information (OSTI.GOV)

Altıntop, Mehlika; Ciftci, Halil; Radwan, Mohamed

In an attempt to develop potent antitumor agents, new 1,3,4-thiadiazole derivatives were synthesized and evaluated for their cytotoxic effects on multiple human cancer cell lines, including the K562 chronic myelogenous leukemia cell line that expresses the Bcr-Abl tyrosine kinase. N-(5-Nitrothiazol-2-yl)-2-((5-((4-(trifluoromethyl)phenyl)amino)-1,3,4-thiadiazol-2-yl)thio)acetamide (2) inhibited the Abl protein kinase with an IC 50 value of 7.4 µM and showed selective activity against the Bcr-Abl positive K562 cell line. Furthermore, a Bcr-Abl-compound 2 molecular modelling simulation highlighted the anchoring role of the nitrothiazole moiety in bonding and hydrophobic interaction with the key amino acid residues. These results provide promising starting points for further developmentmore » of novel kinase inhibitors.« less

Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.

PubMed

Zhou, Zhuxian; Ma, Xinpeng; Murphy, Caitlin J; Jin, Erlei; Sun, Qihang; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J

2014-10-06

The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and anti-cancer potential of the positional isomers of NOSH-aspirin (NBS-1120) a dual nitric oxide and hydrogen sulfide releasing hybrid.

PubMed

Vannini, Federica; MacKessack-Leitch, Andrew C; Eschbach, Erin K; Chattopadhyay, Mitali; Kodela, Ravinder; Kashfi, Khosrow

2015-10-15

We recently reported the synthesis of NOSH-aspirin, a novel hybrid compound capable of releasing both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e., ortho-NOSH-aspirin. Here we report on the synthesis of meta- and para-NOSH-aspirins. We also made a head-to-head evaluation of the effects of these three positional isomers of NOSH-aspirin on colon cancer cell kinetics and induction of reactive oxygen species, which in recent years has emerged as a key event in causing cancer cell regression. Electron donating/withdrawing groups incorporated about the benzoate moiety significantly affected the potency of these compounds with respect to colon cancer cell growth inhibition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis, structurale elucidation and antioxidant study of Ortho-substituted N,N’-bis(benzamidothiocarbonyl)hydrazine derivatives

NASA Astrophysics Data System (ADS)

Firdausiah, Syadza; Hasbullah, S. A.; Yamin, B. M.

2018-03-01

Some bis(thiourea) compounds have been reported to posses excellent performance in pharmaceutical and environmental fields because of their ability to form chelating complexes with various anions and metal ions. Structurally for carbonyl thiourea derivatives, to become a chelating agent, it must adopt cis-configuration. In the present study, four new bis(thiourea) derivatives namely N,N’-bis(o-fluorobenzamidothiocarbonyl)hydrazine (1), N,N’- bis(o-chloro-benzamidothiocarbonyl)hydrazine (2), N,N’-bis(o-nitrobenzamidothiocarbonyl)-hydrazine (3), and N,N’-bis(o-methylbenzamidothiocarbonyl)hydrazine (4) were successfully synthesized and characterized by CHNS microelemental analysis, FTIR, UV-Vis, and 1H and 13C NMR spectroscopy. However chemical crystallography study showed that both thiourea moieties in compound (2) and (3) adopt trans geometry. Therefore they are potential monodentate ligand with two active moieties. DPPH radical scavenging experiment showed that compound (1), (2), and (4) exhibited higher antioxidant activity than ascorbic acid (Vitamin C).

Methods for neutralizing anthrax or anthrax spores

DOEpatents

Sloan, Mark A; Vivekandanda, Jeevalatha; Holwitt, Eric A; Kiel, Johnathan L

2013-02-26

The present invention concerns methods, compositions and apparatus for neutralizing bioagents, wherein bioagents comprise biowarfare agents, biohazardous agents, biological agents and/or infectious agents. The methods comprise exposing the bioagent to an organic semiconductor and exposing the bioagent and organic semiconductor to a source of energy. Although any source of energy is contemplated, in some embodiments the energy comprises visible light, ultraviolet, infrared, radiofrequency, microwave, laser radiation, pulsed corona discharge or electron beam radiation. Exemplary organic semiconductors include DAT and DALM. In certain embodiments, the organic semiconductor may be attached to one or more binding moieties, such as an antibody, antibody fragment, or nucleic acid ligand. Preferably, the binding moiety has a binding affinity for one or more bioagents to be neutralized. Other embodiments concern an apparatus comprising an organic semiconductor and an energy source. In preferred embodiments, the methods, compositions and apparatus are used for neutralizing anthrax spores.

The Solid-Phase Synthesis of an Fe-N-C Electrocatalyst for High-Power Proton-Exchange Membrane Fuel Cells.

PubMed

Liu, Qingtao; Liu, Xiaofang; Zheng, Lirong; Shui, Jianglan

2018-01-26

The environmentally friendly synthesis of highly active Fe-N-C electrocatalysts for proton-exchange membrane fuel cells (PEMFCs) is desirable but remains challenging. A simple and scalable method is presented to fabricate Fe II -doped ZIF-8, which can be further pyrolyzed into Fe-N-C with 3 wt % of Fe exclusively in Fe-N 4 active moieties. Significantly, this Fe-N-C derived acidic PEMFC exhibits an unprecedented current density of 1.65 A cm -2 at 0.6 V and the highest power density of 1.14 W cm -2 compared with previously reported NPMCs. The excellent PEMFC performance can be attributed to the densely and atomically dispersed Fe-N 4 active moieties on the small and uniform catalyst nanoparticles. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Position-specific incorporation of fluorescent non-natural amino acids into maltose-binding protein for detection of ligand binding by FRET and fluorescence quenching.

PubMed

Iijima, Issei; Hohsaka, Takahiro

2009-04-17

Position-specific incorporation of fluorescent groups is a useful method for analysis of the functions and structures of proteins. We have developed a method for the incorporation of visible-wavelength-fluorescent non-natural amino acids into proteins in a cell-free translation system. Using this technique, we introduced one or two BODIPY-linked amino acids into maltose-binding protein (MBP) to obtain MBP derivatives showing ligand-dependent changes in fluorescence intensity or intensity ratio. BODIPY-FL-aminophenylalanine was incorporated in place of 15 tyrosines, as well as the N-terminal Lys1, and the C-terminal Lys370 of MBP. Fluorescence measurements revealed that MBP containing a BODIPY-FL moiety in place of Tyr210 showed a 13-fold increase in fluorescence upon binding of maltose. Tryptophan-to-phenylalanine substitutions suggest that the increase in fluorescence was the result of a decrease in the quenching of BODIPY-FL by tryptophan located around the binding site. MBP containing a BODIPY-558 moiety also showed a maltose-dependent increase in fluorescence. BODIPY-FL was then additionally incorporated in place of Lys1 of the BODIPY-558-containing MBP as a response to the amber codon. Fluorescence measurements with excitation of BODIPY-FL showed a large change in fluorescence intensity ratio (0.13 to 1.25) upon binding of maltose; this change can be attributed to fluorescence resonance energy transfer (FRET) and maltose-dependent quenching of BODIPY-558. These results demonstrate the usefulness of the position-specific incorporation of fluorescent amino acids in the fluorescence-based detection of protein functions.

Electrophile-modified lipoic derivatives of PDC-E2 elicits anti-mitochondrial antibody reactivity.

PubMed

Naiyanetr, Phornnop; Butler, Jeffrey D; Meng, Liping; Pfeiff, Janice; Kenny, Thomas P; Guggenheim, Kathryn G; Reiger, Roman; Lam, Kit; Kurth, Mark J; Ansari, Aftab A; Coppel, Ross L; López-Hoyos, Marcos; Gershwin, M Eric; Leung, Patrick S C

2011-11-01

Our laboratory has hypothesized that xenobiotic modification of the native lipoyl moiety of the major mitochondrial autoantigen, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), may lead to loss of self-tolerance in primary biliary cirrhosis (PBC). This thesis is based on the finding of readily detectable levels of immunoreactivity of PBC sera against extensive panels of protein microarrays containing mimics of the inner lipoyl domain of PDC-E2 and subsequent quantitative structure-activity relationships (QSARs). Importantly, we have demonstrated that murine immunization with one such mimic, 2-octynoic acid coupled to bovine serum albumin (BSA), induces anti-mitochondrial antibodies (AMAs) and cholangitis. Based upon these data, we have focused on covalent modifications of the lipoic acid disulfide ring and subsequent analysis of such xenobiotics coupled to a 15mer of PDC-E2 for immunoreactivity against a broad panel of sera from patients with PBC and controls. Our results demonstrate that AMA-positive PBC sera demonstrate marked reactivity against 6,8-bis(acetylthio)octanoic acid, implying that chemical modification of the lipoyl ring, i.e. disruption of the S-S disulfide, renders lipoic acid to its reduced form that will promote xenobiotic modification. This observation is particularly significant in light of the function of the lipoyl moiety in electron transport of which the catalytic disulfide constantly opens and closes and, thus, raises the intriguing thesis that common electrophilic agents, i.e. acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs), may lead to xenobiotic modification in genetically susceptible individuals that results in the generation of AMAs and ultimately clinical PBC. Copyright © 2011 Elsevier Ltd. All rights reserved.

Boron-containing acids: preliminary evaluation of acute toxicity and access to the brain determined by Raman scattering spectroscopy.

PubMed

Soriano-Ursúa, Marvin A; Farfán-García, Eunice D; López-Cabrera, Yessica; Querejeta, Enrique; Trujillo-Ferrara, José G

2014-01-01

Boron-containing compounds (BCCs), particularly boron containing acids (BCAs), have become attractive moieties or molecules in drug development. It has been suggested that when functional groups with boron atoms are added to well-known drugs, the latter are conferred with greater potency and efficacy in relation to their target receptors. However, the use of BCAs in drug development is limited due to the lack of a toxicological profile. Consequently, the aim of the present study was to evaluate the acute toxicity of boric and boronic acids. Thus, a determination was made of the lethal dose (LD50) of test compounds in male CD1 mice, as well as the effective dose required to negatively affect spontaneous motor activity and to produce notable behavioral abnormalities. After treatment of animals at different doses, macroscopic observations were made from a necropsy, and Raman scattering spectroscopic studies were carried out on brain tissue samples. In general, the results show that most of the tested BCAs have very low toxicity, evidenced by the high doses required to induce notable toxic effects (greater than 100 mg/kg of body weight for all compounds, except for 3-thyenilboronic acid). Such toxic effects, presumably mediated by action on the CNS, include eye damage, gastrointestinal effects (e.g., gastric-gut dilatation and fecal retention), sedation, hypnosis and/or trembling. This preliminary toxicological profile suggests that BCAs can be considered potential therapeutic agents or moieties to be added to other compounds in the development of new drugs. Future studies are required to explore possible chronic toxicity of BCCs. Copyright © 2013 Elsevier Inc. All rights reserved.

Polydiacetylene liposomes with phenylboronic acid tags: a fluorescence turn-on sensor for sialic acid detection and cell-surface glycan imaging.

PubMed

Wang, Dong-En; Yan, Jiahang; Jiang, Jingjing; Liu, Xiang; Tian, Chang; Xu, Juan; Yuan, Mao-Sen; Han, Xiang; Wang, Jinyi

2018-03-01

Sialic acid (SA) located at the terminal end of glycans on cell membranes has been shown to play an important yet distinctive role in various biological and pathological processes. Effective methods for the facile, sensitive and in situ analysis of SA on living cell surfaces are of great significance in terms of clinical diagnostics and therapeutics. Here, a new polydiacetylene (PDA) liposome-based sensor system bearing phenylboronic acid (PBA) and 1,8-naphthalimide derived fluorophore moieties was developed as a fluorescence turn-on sensor for the detection of free SA in aqueous solution and the in situ imaging of SA-terminated glycans on living cell surfaces. In the sensor system, three diacetylene monomers, PCDA-pBA, PCDA-Nap and PCDA-EA, were designed and synthesized to construct the composite PDA liposome sensor. The monomer PCDA-pBA modified with PBA molecules was employed as a receptor for SA recognition, while the monomer PCDA-Nap containing a 1,8-naphthalimide derivative fluorophore was used for fluorescence signaling. When the composite PDA liposomes were formed, the energy transfer between the fluorophore and the conjugated backbone could directly quench the fluorescence of the fluorophore. In the presence of additional SA or SA abundant cells, the strong binding of SA with PBA moieties disturbed the pendent side chain conformation, resulting in the fluorescence restoration of the fluorophore. The proposed methods realized the fluorescence turn-on detection of free SA in aqueous solution and the in situ imaging of SA on living MCF-7 cell surfaces. This work provides a new potential tool for simple and selective analysis of SA on living cell membranes.

Discovery and preclinical development of a novel prodrug conjugate of mesalamine with eicosapentaenoic acid and caprylic acid for the treatment of inflammatory bowel diseases.

PubMed

Kandula, Mahesh; Sunil Kumar, K B; Palanichamy, Sivanesan; Rampal, Ashok

2016-11-01

Mesalamine (5-ASA) is one of the drugs indicated as first line therapy in ulcerative colitis for induction and maintenance of remission. Sulfasalazine and formulations of 5-ASA (pH-dependent and controlled release formulations) were developed to minimize the systemic absorption and maximize the delivery of the mesalamine to colon. Although, its efficacy and safety is well documented there are approximately 30% nonresponders to 5-ASA therapy. This necessitates the need for novel therapeutic options to improve the efficacy and safety of the currently available 5-ASA therapy. CLX-103 is a novel, patented prodrug molecular conjugate of mesalamine, eicosapentaenoic acid and caprylic acid designed to offer incremental benefits over the currently approved 5-ASA formulations. Results of in vitro and in vivo studies showed that CLX-103, was stable in simulated gastric fluid, but undergoes enzymatic hydrolysis in the small/large intestines to release the active moiety. Our data also showed that the active moiety is retained in the targeted intestinal tissues (ileum and colon) over a longer period of time in relation to sulfasalazine. The in vitro data supports the observed in vivo plasma kinetics of 5-ASA characterized by longer T max , low C max after the oral administration of CLX-103. Efficacy study of CLX-103 in acute dextran sodium sulfate (DSS) mouse colitis model showed improved potency measured as Disease Activity Index (DAI) and histological scores in the colon as compared to sulfasalazine. These findings indicate that CLX-103 could offer a differentiated drug product which is more efficacious and safer than the currently approved 5-ASA formulations in the treatment of inflammatory bowel diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of Novel Fusaricidins Produced by Paenibacillus polymyxa-M1 Using MALDI-TOF Mass Spectrometry

NASA Astrophysics Data System (ADS)

Vater, Joachim; Niu, Ben; Dietel, Kristin; Borriss, Rainer

2015-09-01

Paenibacillus polymyxa-M1 is a potent producer of bioactive compounds, such as lipopeptides, polyketides, and lantibiotics of biotechnological and medical interest. Genome sequencing revealed nine gene clusters for nonribosomal biosynthesis of such agents. Here we report on the investigation of the fusaricidins, a complex of cyclic lipopeptides containing 15-guanidino-3-hydroxypentadecanoic acid (GHPD) as fatty acid component by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). More than 20 variants of these compounds were detected and characterized in detail. Mass spectrometric sequence analysis was performed by MALDI-LIFT-TOF/TOF fragment analysis. The obtained product ion spectra show a specific processing in the fatty acid part. GHPD is cleaved between the α- and ß-position yielding two fragments a and b, one bearing the end-standing guanidine group and another one comprising the residual two C-atoms of GHPD with the attached peptide moiety. The complete sequence of all fusaricidins was derived from sets of bn- and yn-ions. The fusaricidin complex can be divided into four lipopeptide families, three of them showing variations of the amino acid in position 3, Val or Ile for the first and Tyr or Phe for families 2 and 3, respectively. A collection of novel fusaricidins was detected differing from those of families 1-3 by an additional residue of 71 Da (family 4). LIFT-TOF/TOF fragment spectra of these species imply that in their peptide moiety, an Ala-residue is attached by an ester bond to the free hydroxyl group of Thr4. More than 10 novel fusaricidins were characterized mass spectrometrically.

Absorption, fluorescence, and acid-base equilibria of rhodamines in micellar media of sodium dodecyl sulfate

NASA Astrophysics Data System (ADS)

Obukhova, Elena N.; Mchedlov-Petrossyan, Nikolay O.; Vodolazkaya, Natalya A.; Patsenker, Leonid D.; Doroshenko, Andrey O.; Marynin, Andriy I.; Krasovitskii, Boris M.

2017-01-01

Rhodamine dyes are widely used as molecular probes in different fields of science. The aim of this paper was to ascertain to what extent the structural peculiarities of the compounds influence their absorption, emission, and acid-base properties under unified conditions. The acid-base dissociation (HR+ ⇄ R + H+) of a series of rhodamine dyes was studied in sodium n-dodecylsulfate micellar solutions. In this media, the form R exists as a zwitterion R±. The indices of apparent ionization constants of fifteen rhodamine cations HR+ with different substituents in the xanthene moiety vary within the range of pKaapp = 5.04 to 5.53. The distinct dependence of emission of rhodamines bound to micelles on pH of bulk water opens the possibility of using them as fluorescent interfacial acid-base indicators.

Incorporation of Amino Acids with Long-Chain Terminal Olefins into Proteins.

PubMed

Exner, Matthias P; Köhling, Sebastian; Rivollier, Julie; Gosling, Sandrine; Srivastava, Puneet; Palyancheva, Zheni I; Herdewijn, Piet; Heck, Marie-Pierre; Rademann, Jörg; Budisa, Nediljko

2016-02-29

The increasing need for site-specific protein decorations that mimic natural posttranslational modifications requires access to a variety of noncanonical amino acids with moieties enabling bioorthogonal conjugation chemistry. Here we present the incorporation of long-chain olefinic amino acids into model proteins with rational variants of pyrrolysyl-tRNA synthetase (PylRS). Nε-heptenoyl lysine was incorporated for the first time using the known promiscuous variant PylRS(Y306A/Y384F), and Nε-pentenoyl lysine was incorporated in significant yields with the novel variant PylRS(C348A/Y384F). This is the only example of rational modification at position C348 to enlarge the enzyme's binding pocket. Furthermore, we demonstrate the feasibility of our chosen amino acids in the thiol-ene conjugation reaction with a thiolated polysaccharide.

SERS spectrum of gallic acid obtained from a modified silver colloid

NASA Astrophysics Data System (ADS)

Garrido, C.; Diaz-Fleming, G.; Campos-Vallette, M. M.

2016-06-01

Two different crystals of the gallic acid were microscopically separated from a p.a. commercial product. The Raman spectra analysis allowed distinguishing monomeric and dimeric structures. The vibrational wave numbers were computed using DFT quantum chemical calculations. The data obtained from wave number calculations are used to assign vibrational bands obtained in the Raman spectrum. The dimer, characterized as ellagic acid, involves the carboxyl and hydroxyl moieties. The Raman spectrum in water solution of each species is dominated by the monomeric form. A low negatively charged Ag colloid allowed obtain to the best of our knowledge, the first surface enhanced Raman scattering (SERS) spectrum of the gallic acid. The possible electrophilic attacking sites of the title molecule are identified using MEP surface plot study and the orientation of the analyte on the metal surface is proposed tilted to the surface.

Plasmid DNA-encapsulating liposomes: effect of a spacer between the cationic head group and hydrophobic moieties of the lipids on gene expression efficiency.

PubMed

Obata, Yosuke; Saito, Shunsuke; Takeda, Naoya; Takeoka, Shinji

2009-05-01

We have synthesized a series of cationic amino acid-based lipids having a spacer between the cationic head group and hydrophobic moieties and examined the influence of the spacer on a liposome gene delivery system. As a comparable spacer, a hydrophobic spacer with a hydrocarbon chain composed of 0, 3, 5, 7, or 11 carbons, and a hydrophilic spacer with an oxyethylene chain (10 carbon and 3 oxygen molecules) were investigated. Plasmid DNA (pDNA)-encapsulating liposomes were prepared by mixing an ethanol solution of the lipids with an aqueous solution of pDNA. The zeta potentials and cellular uptake efficiency of the cationic liposomes containing each synthetic lipid were almost equivalent. However, the cationic lipids with the hydrophobic spacer were subject to fuse with biomembrane-mimicking liposomes. 1,5-Dihexadecyl-N-lysyl-N-heptyl-l-glutamate, having a seven carbon atom spacer, exhibited the highest fusogenic potential among the synthetic lipids. Increased fusion potential correlated with enhanced gene expression efficiency. By contrast, an oxyethylene chain spacer showed low gene expression efficiency. We conclude that a hydrophobic spacer between the cationic head group and hydrophobic moieties is a key component for improving pDNA delivery.

Rapid Identification of unstable acyl glucoside flavonoids of Oxytropis racemosa Turcz by high-performance liquid chromatography-diode array detection-electrospray ionisation/multi-stage mass spectrometry.

PubMed

Song, Shuang; Zheng, Xiu-Ping; Liu, Wei-Dong; Du, Rui-Fang; Feng, Zi-Ming; Zhang, Pei-Cheng; Bi, Li-Fu

2013-02-01

Oxytropis racemosa Turcz is an important minority medicine that is used mainly to improve children's indigestion, especially in inner Mongolia and Tibet. Previous studies indicated that the characteristic constituents of this plant are acylated flavonoids. Rapidly identify the characteristic chemical constituents of O. racemosa by high-performance liquid chromatography-diode array detection-electrospray ionisation/multi-stage mass spectrometry (HPLC-DAD-ESI/MS(n) ) and suggest a useful method to control the quality of this medicinal plant. In the HPLC fingerprint, 32 flavonoids were tentatively identified by a detailed analysis of their mass spectra, UV spectra and retention times. Furthermore, 13 flavonoids were confirmed by comparison with previously isolated compounds obtained from O. racemosa. In total, 32 flavonoids, including 13 flavonoids with 3-hydroxy-3-methylglutaric acid (HMG) moieties and four flavonoids with 3-malonyl moieties, were identified in the extract of O. racemosa. Among the compounds identified, 10 were characterised as new compounds for their particular acylated sugar moieties. The method described is effective for obtaining a comprehensive phytochemical profile of plants containing unstable acylated flavonoids. The method is also useful for constructing the chromatographic fingerprint of the minority medicine -O. racemosa Turcz for quality control. Copyright © 2012 John Wiley & Sons, Ltd.

Antioxidant properties of ferulic acid and its related compounds.

PubMed

Kikuzaki, Hiroe; Hisamoto, Masashi; Hirose, Kanae; Akiyama, Kayo; Taniguchi, Hisaji

2002-03-27

Antioxidant activity of 24 ferulic acid related compounds together with 6 gallic acid related compounds was evaluated using several different physical systems as well as their radical scavenging activity. The radical scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) decreased in the order caffeic acid > sinapic acid > ferulic acid > ferulic acid esters > p-coumaric acid. In bulk methyl linoleate, test hydroxycinnamic acids and ferulic acid esters showed antioxidant activity in parallel with their radical scavenging activity. In an ethanol-buffer solution of linoleic acid, the activity of test compounds was not always associated with their radical scavenging activity. Ferulic acid was most effective among the tested phenolic acids. Esterification of ferulic acid resulted in increasing activity. The activity of alkyl ferulates was somewhat influenced by the chain length of alcohol moiety. When the inhibitory effects of alkyl ferulates against oxidation of liposome induced by AAPH were tested, hexyl, octyl, and 2-ethyl-1-hexyl ferulates were more active than the other alkyl ferulates. Furthermore, lauryl gallate is most effective among the tested alkyl gallates. These results indicated that not only the radical scavenging activity of antioxidants, but also their affinity with lipid substrates, might be important factors in their activity.

Identification of furan fatty acids in the lipids of common carp (Cyprinus carpio L.).

PubMed

Chvalová, Daniela; Špička, Jiří

2016-06-01

Fatty acid (FA) composition was analyzed in muscle and gonad tissues of marketed common carp (Cyprinus carpio). The extracted lipids were separated into four fractions: polar lipids (PL), diacylglycerols, free fatty acids and triacylglycerols (TAG) using thin layer chromatography. FA content within the lipid fractions was determined by gas chromatography with flame ionization detector (GC/FID). The muscle lipids consisted primarily of TAG (96.9% of total FA), while PL were the major component of both male (67.6%) and female gonad (58.6%) lipids. Polyunsaturated fatty acids predominated in PL of all tissues (52.2-55.8% of total FA); monounsaturated fatty acids were the most abundant FA group in TAG of muscle (51.8%) and female gonads (47.8%) whereas high proportion of furan fatty acids (F-acids) (38.2%) was detected in TAG of male gonads. Eight F-acids were identified by gas chromatography-mass spectrometry (GC/MS) in male gonad samples, including less common 12,15-epoxy-13,14-dimethylnonadeca-12,14-dienoic acid with even-numbered alkyl moiety. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structure-Activity Correlations with Compounds Related to Abscisic Acid 1

PubMed Central

Sondheimer, Ernest; Walton, Daniel C.

1970-01-01

Inhibition of cell expansion of excised embryonic axes of Phaseolus vulgaris was used to evaluate the growth-inhibiting activity of abscisic acid and related compounds. None of the 13 compounds tested was as active as abscisic acid. 4-Hydroxyisophorone, a substance representative of the abscisic acid ring system was essentially inactive; cis, trans-3-methylsorbic acid, a compound resembling the side chain of abscisic acid, had low activity; and cis, trans-β-ionylideneacetic acid was one-sixth as active. Loss of the ring double bond results in a drastic decrease in biological activity. Comparison of our results with those reported previously leads to the suggestion that the double bond of the cyclohexyl moiety may have an important function in determining the degree of activity of cis, trans-ionylideneacetic acids. Two modes of action are discussed. It seems possible that the ring double bond is involved in covalent bonding in binding of the abscisic acid analogue to macromolecules. This may require formation of an intermediate epoxide. It can also be argued that stereochemical differences between cyclohexane derivatives are important factors in determining the degree of biological activity. PMID:5423465

Presynaptic (Type III) cells in mouse taste buds sense sour (acid) taste.

PubMed

Huang, Yijen A; Maruyama, Yutaka; Stimac, Robert; Roper, Stephen D

2008-06-15

Taste buds contain two types of cells that directly participate in taste transduction - receptor (Type II) cells and presynaptic (Type III) cells. Receptor cells respond to sweet, bitter and umami taste stimulation but until recently the identity of cells that respond directly to sour (acid) tastants has only been inferred from recordings in situ, from behavioural studies, and from immunostaining for putative sour transduction molecules. Using calcium imaging on single isolated taste cells and with biosensor cells to identify neurotransmitter release, we show that presynaptic (Type III) cells specifically respond to acid taste stimulation and release serotonin. By recording responses in cells isolated from taste buds and in taste cells in lingual slices to acetic acid titrated to different acid levels (pH), we also show that the active stimulus for acid taste is the membrane-permeant, uncharged acetic acid moiety (CH(3)COOH), not free protons (H(+)). That observation is consistent with the proximate stimulus for acid taste being intracellular acidification, not extracellular protons per se. These findings may also have implications for other sensory receptors that respond to acids, such as nociceptors.

Amino acid analogs for tumor imaging

DOEpatents

Goodman, M.M.; Shoup, T.

1998-09-15

The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

Amino acid analogs for tumor imaging

DOEpatents

Goodman, M.M.; Shoup, T.

1998-10-06

The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

Amino acid analogs for tumor imaging

DOEpatents

Goodman, Mark M.; Shoup, Timothy

1998-09-15

The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

Amino acid analogs for tumor imaging

DOEpatents

Goodman, Mark M.; Shoup, Timothy

1998-10-06

The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

Chemical constituents from roots of Taraxacum formosanum.

PubMed

Leu, Yann-Lii; Wang, Yu-Li; Huang, Shih-Chin; Shi, Li-Shian

2005-07-01

Two new compounds, taraxafolide (1) and (+)-taraxafolin-B (2) together with eighteen known compounds, which include one sesquiterpene, thirteen benzenoids, two indole alkaloids, one pyridine derivative and steroid mixtures were isolated and characterized from the fresh roots of Taraxacum formosanum. Structures of new compounds were determined by spectral analysis. (+)-Taraxafolin-B had the bioactive caffeic acid moiety, but its activity was weaker than alpha-tocopherol in DPPH radicals scavenging activity assay.

In situ generation of N-Boc-protected alkenyl imines: controlling the E/Z geometry of alkenyl moieties in the Mukaiyama-Mannich reaction.

PubMed

Bai, Jian-Fei; Sasagawa, Hajime; Yurino, Taiga; Kano, Taichi; Maruoka, Keiji

2017-07-18

Readily available Boc-protected Z-alkenyl aminals could be used as Z-alkenyl and E-alkenyl imine precursors under acidic conditions. In the Mukaiyama-Mannich reaction of Z-alkenyl Boc-aminals, the E/Z geometry of the products was controlled by the catalyst used. The present method was also applied to asymmetric Mukaiyama-Mannich reactions.

Tertiary nitrogen heterocyclic material to reduce moisture-induced damage in asphalt-aggregate mixtures

DOEpatents

Plancher, Henry; Petersen, Joseph C.

1982-01-01

Asphalt-aggregate roads crack when subjected to freezing and thawing cycles. Herein, the useful life of asphalts are substantially improved by a minor amount of a moisture damage inhibiting agent selected from compounds having a pyridine moiety, including acid salts of such compounds. A shale oil fraction may serve as the source of the improving agent and may simply be blended with conventional petroleum asphalts.

A Pauson-Khand approach to the hamigerans.

PubMed

Madu, Christian E; Lovely, Carl J

2007-11-08

An intramolecular Pauson-Khand reaction has been used in the construction of the tricyclic core common to the hamigeran terpenes. For effective cyclization, it was necessary to tether the olefin-containing moiety to the aromatic framework to reduce its conformation mobility; this was accomplished using a silylene protecting group. Efficient construction of the aryl enyne from a salicylic acid derivative was accomplished via ortho lithiation and Sonogashira cross-coupling chemistry.

Photoremovable chiral auxiliary.

PubMed

Kammath, Viju Balachandran; Sebej, Peter; Slanina, Tomáš; Kříž, Zdeněk; Klán, Petr

2012-03-01

A new concept of a photoremovable chiral auxiliary (PCA), based on the chiral benzoin chromophore, is introduced. This moiety can control the asymmetric formation of a Diels-Alder adduct, and then be removed in a subsequent photochemical step in high chemical and quantum yields. Selective formation of the products at up to 96% ee was observed in the presence of a Lewis acid catalyst in the case of a 2-methoxybenzoinyl chiral auxiliary.

A simple chromatographic method for purification of egg lecithin.

PubMed

Nielsen, J R

1980-06-01

Egg lecithin was purified from the CdCl2-lecithin complex by column chromatography on Alumina. The yield from 5 eggs was 2.8 g. The purified lecithin had correct chemical values for pure lecithin and a fatty acid composition similar to lecithin prepared by other methods. The method probably can be adapted for purification of other lipids containing the phosphocholine moiety and for purification of synthetic lecithin.

The gamma subunit of transducin is farnesylated.

PubMed Central

Lai, R K; Perez-Sala, D; Cañada, F J; Rando, R R

1990-01-01

Protein prenylation with farnesyl or geranylgeranyl moieties is an important posttranslational modification that affects the activity of such diverse proteins as the nuclear lamins, the yeast mating factor mata, and the ras oncogene products. In this article, we show that whole retinal cultures incorporate radioactive mevalonic acid into proteins of 23-26 kDa and one of 8 kDa. The former proteins are probably the "small" guanine nucleotide-binding regulatory proteins (G proteins) and the 8-kDa protein is the gamma subunit of the well-studied retinal heterotrimeric G protein (transducin). After deprenylating purified transducin and its subunits with Raney nickel or methyl iodide/base, the adducted prenyl group can be identified as an all-trans-farnesyl moiety covalently linked to a cysteine residue. Thus far, prenylation reactions have been found to occur at cysteine in a carboxyl-terminal consensus CAAX sequence, where C is the cysteine, A is an aliphatic amino acid, and X is undefined. Both the alpha and gamma subunits of transducin have this consensus sequence, but only the gamma subunit is prenylated. Therefore, the CAAX motif is not necessary and sufficient to direct prenylation. Finally, since transducin is the best understood G protein, both structurally and mechanistically, the discovery that it is farnesylated should allow for a quantitative understanding of this post-translational modification. Images PMID:2217200

Novel Aeruginosin-865 from Nostoc sp. as a potent anti-inflammatory agent.

PubMed

Kapuścik, Aleksandra; Hrouzek, Pavel; Kuzma, Marek; Bártová, Simona; Novák, Petr; Jokela, Jouni; Pflüger, Maren; Eger, Andreas; Hundsberger, Harald; Kopecký, Jiří

2013-11-25

Aeruginosin-865 (Aer-865), isolated from terrestrial cyanobacterium Nostoc sp. Lukešová 30/93, is the first aeruginosin-type peptide containing both a fatty acid and a carbohydrate moiety, and is the first aeruginosin to be found in the genus Nostoc. Mass spectrometry, chemical and spectroscopic analysis as well as one- and two-dimensional NMR and chiral HPLC analysis of Marfey derivatives were applied to determine the peptidic sequence: D-Hpla, D-Leu, 5-OH-Choi, Agma, with hexanoic and mannopyranosyl uronic acid moieties linked to Choi. We used an AlphaLISA assay to measure the levels of proinflammatory mediators IL-8 and ICAM-1 in hTNF-α-stimulated HLMVECs. Aer-865 showed significant reduction of both: with EC50 values of (3.5±1.5) μg mL(-1) ((4.0±1.7) μM) and (50.0±13.4) μg mL(-1) ((57.8±15.5) μM), respectively. Confocal laser scanning microscopy revealed that the anti-inflammatory effect of Aer-865 was directly associated with inhibition of NF-κB translocation to the nucleus. Moreover, Aer-865 did not show any cytotoxic effect. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spatial Associations and Chemical Composition of Organic Carbon Sequestered in Fe, Ca, and Organic Carbon Ternary Systems.

PubMed

Sowers, Tyler D; Adhikari, Dinesh; Wang, Jian; Yang, Yu; Sparks, Donald L

2018-05-25

Organo-mineral associations of organic carbon (OC) with iron (Fe) oxides play a major role in environmental OC sequestration, a process crucial to mitigating climate change. Calcium has been found to have high coassociation with OC in soils containing high Fe content, increase OC sorption extent to poorly crystalline Fe oxides, and has long been suspected to form bridging complexes with Fe and OC. Due to the growing realization that Ca may be an important component of C cycling, we launched a scanning transmission X-ray microscopy (STXM) investigation, paired with near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, in order to spatially resolve Fe, Ca, and OC relationships and probe the effect of Ca on sorbed OC speciation. We performed STXM-NEXAFS analysis on 2-line ferrihydrite reacted with leaf litter-extractable dissolved OC and citric acid in the absence and presence of Ca. Organic carbon was found to highly associate with Ca ( R 2 = 0.91). Carboxylic acid moieties were dominantly sequestered; however, Ca facilitated the additional sequestration of aromatic and phenolic moieties. Also, C NEXAFS revealed polyvalent metal ion complexation. Our results provide evidence for the presence of Fe-Ca-OC ternary complexation, which has the potential to significantly impact how organo-mineral associations are modeled.

A comparison of an ATPase from the archaebacterium Halobacterium saccharovorum with the F1 moiety from the Escherichia coli ATP Synthase

NASA Technical Reports Server (NTRS)

Stan-Lotter, Helga; Hochstein, Lawrence I.

1989-01-01

A purified ATPase associated with membranes from Halobacterium saccharovorum was compared with the F sub 1 moiety from the Escherichia coli ATP Synthase. The halobacterial enzyme was composed of two major (I and II) and two minor subunits (III and IV), whose molecular masses were 87 kDa, 60 kDa, 29 kDa, and 20 kDa, respectively. The isoelectric points of these subunits ranged from 4.1 to 4.8, which in the case of the subunits I and II was consistent with the presence of an excess of acidic amino acids (20 to 22 Mol percent). Peptide mapping of sodium dodecylsulfate-denatured subunits I and II showed no relationship between the primary structures of the individual halobacterial subunits or similarities to the subunits of the F sub 1 ATPase (EC 3.6.1.34) from E. coli. Trypsin inactivation of the halobacterial ATPase was accompanied by the partial degradation of the major subunits. This observation, taken in conjunction with molecular masses of the subunits and the native enzyme, was consistent with the previously proposed stoichiometry of 2:2:1:1. These results suggest that H. saccharovorum, and possibly, Halobacteria in general, possess an ATPase which is unlike the ubiquitous F sub o F sub 1 - ATP Synthase.

Metabolite characterization of a novel anti-cancer agent, icotinib, in humans through liquid chromatography/quadrupole time-of-flight tandem mass spectrometry.

PubMed

Liu, Dongyang; Jiang, Ji; Zhang, Li; Tan, Fenlai; Wang, Yingxiang; Hu, Pei

2011-08-15

Icotinib is a novel anti-cancer drug that has shown promising clinical efficacy and safety in patients with non-small-cell lung cancer (NSCLC). At this time, the metabolic fate of icotinib in humans is unknown. In the present study, a liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (LC/Q-TOF MS) method was established to characterize metabolites of icotinib in human plasma, urine and feces. In addition, nuclear magnetic resonance (NMR) detection was utilized to determine the connection between side-chain and quinazoline groups for some complex metabolites. In total, 29 human metabolites (21 isomer metabolites) were characterized, of which 23 metabolites are novel compared to the metabolites in rats. This metabolic study revealed that icotinib was extensively metabolized at the 12-crown-4 ether moiety (ring-opening and further oxidation), carbon 15 (hydroxylation) and an acetylene moiety (oxidation) to yield 19 oxidized metabolites and to further form 10 conjugates with sulfate acid or glucuronic acid. To our knowledge, this is the first report of the human metabolic profile of icotinib. Study results indicated that significant attention should be paid to the metabolic profiles of NSCLC patients during the development of icotinib. Copyright © 2011 John Wiley & Sons, Ltd.

Further Insights on the Chemical Structure of Humic Substances (HS) and Chromophoric Dissolved Organic Matter (CDOM) in Relation to their Optical/Chemical Properties

NASA Astrophysics Data System (ADS)

Del Vecchio, R.; Schendorf, T. M.; Koech, K.; Blough, N. V.

2016-02-01

HS have been studied extensively over the last decades, yet the structural basis of their optical properties is still highly debated. Aromatic ketones, aldehydes and quinones along with carboxylic groups and phenolic moieties are significant constituents of HS, however their contribution to the optical properties has only recently been investigated. Chemical manipulation of selected functional groups thus represents an extremely promising approach to highlight the contribution of such groups to the HS (and CDOM) optical properties. Chemical reduction (and re-oxidation) along with pH titrations are employed herein to assess the relative contribution of aromatic ketones/aldehydes/quinones and carboxylic groups/phenolic moieties, respectively to the optical properties of HS (and CDOM). Results indicate that (a) the contribution of quinones to HS absorption and fluorescence is minor (or nil), while that of aromatic ketones (and aldehydes) is significant; (b) phenolic groups contribute more than carboxylic acids to the HS optical properties; (c) the effects of borohydride reduction and pH on the long-wavelength absorption and fluorescence is consistent with charge-transfer interactions between carbonyl and phenolic groups (as well as aromatic carboxylic acids, but to a smaller extent). Results will be presented within the context of our proposed charge-transfer model.

Characterization and comparison of hydrophobic neutral and hydrophobic acid dissolved organic carbon isolated from three municipal landfill leachates

USGS Publications Warehouse

Nanny, Mark A.; Ratasuk, Nopawan

2002-01-01

The acid-precipitated (AP) and acid-soluble (AS) fractions of the combined hydrophobic neutral and hydrophobic acid dissolved organic carbon (DOC) were isolated from leachate collected from three municipal landfills of different age and redox conditions. The AP and the AS combined hydrophobic neutral and hydrophobic acid DOC comprised 6–15% and 51–66%, respectively, of the leachate nonpurgable organic carbon. Elemental analysis, infra-red spectroscopy, 13C CP-MAS nuclear magnetic resonance spectroscopy and dipolar dephasing experiments, and thermochemolysis gas chromatography/mass spectrometry results showed that the AP and AS fractions of hydrophobic neutral and hydrophobic acid DOC are highly aliphatic, with linear and branching moieties, and less oxidized than most terrestrial and aquatic humic substances. Very little, if any, polysaccharide or cellulose, lignin, or cutin components comprise these fractions. It is hypothesized that a majority of the organic carbon in these fractions originates highly branched, cyclic aliphatic organic compounds.

Phytyl Fatty Acid Esters in the Pulp of Bell Pepper (Capsicum annuum).

PubMed

Krauß, Stephanie; Hammann, Simon; Vetter, Walter

2016-08-17

Phytyl fatty acid esters (PFAE) are esters of fatty acids with the isoprenoid alcohol phytol (3,7R,11R,15-tetramethylhexadec-2E-enol). In this study, PFAE were identified and quantified in bell pepper using gas chromatography with mass spectrometry (GC-MS). All red (n = 14) and yellow (n = 6) samples contained six or seven PFAE at 0.9-11.2 mg/100 g fresh weight. By contrast, PFAE were not detected in green bell pepper samples (n = 3). PFAE might eventually be a source for bioavailable phytol, which can be transformed into phytanic acid by humans. Phytanic acid cannot be properly degraded by patients who suffer from Refsum's disease (tolerable daily intake (TDI) ≤ 10 mg of phytanic acid). The phytol moiety of the PFAE (0.4-5.4 mg/100 g fresh weight) would contribute up to ∼50% to the TDI with the consumption of only one portion of bell pepper fruit pulp.

A "natural" approach: synthesis and cytoxicity of monodesmosidic glycyrrhetinic acid glycosides.

PubMed

Schwarz, Stefan; Siewert, Bianka; Xavier, Nuno M; Jesus, Ana R; Rauter, Amélia P; Csuk, René

2014-01-24

Several pentacyclic triterpenoic acids have shown noteworthy antitumor activity, among them betulinic acid as well as oleanolic acid and derivatives thereof. Glycyrrhetinic acid (GA) exhibits some cytotoxic activity albeit this compound is not as active as betulinic acid, but GA came in the focus of scientific interest since it triggers apoptosis in tumor cells. In addition, it can be extracted from the roots of liquorice in high yields. Previous studies revealed that the introduction of an extra hydrophilic moiety increases the cytotoxicity of these compounds. Thus, a series of GA glycosides was prepared utilizing hexoses as well as pentoses (in D- and L-configuration) by using glycosyl trichloroacetimidates and TMSOTf as catalyst. The compounds were screened for cytotoxic activity against seven human cancer cell lines and the not malignant murine cell line NIH 3T3using a photometric SRB assay. The compounds trigger apoptosis as shown from extra trypan blue and acridine orange/ethidium bromide staining. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The Effects of Polyunsaturated Lipid Components on bilayer Structure

NASA Astrophysics Data System (ADS)

Pramudya, Y.; Kiss, A.; Nguyen, Lam T.; Yuan, J.; Hirst, Linda S.

2007-03-01

Polyunsaturated fatty acids (PUFAs), such as DHA (Docosahexanoic Acid) and AA (Alphalinoleic Acid) have been the focus of much research attention in recent years, due to their apparent health benefits and effects on cell physiology. They are found in a variety of biological membranes and have been implicated with lipid raft formation and possible function, particularly in the retinal rod cells and the central nervous system. In this work lipid bilayer structure has been investigated in lipid mixtures, incorporating polyunsaturated fatty acid moieties. The structural effects of increasing concentrations of both symmetric and asymmetric PUFA materials on the bilayer structure are investigated via synchrotron x-ray diffraction on solution samples. We observe bilayer spacings to increase with the percentage of unsaturated fatty acid lipid in the membrane, whilst the degree of ordering significantly decreases. In fact above 20% of fatty acid, well defined bilayers are no longer observed to form. Evidence of phase separation can be clearly seen from these x-ray results and in combination with AFM measurements.

Acid hydrolysis of crude tannins from infructescence of Platycarya strobilacea Sieb. et Zucc to produce ellagic acid.

PubMed

Zhang, Liangliang; Wang, Yongmei; Xu, Man

2014-01-01

The infructescence of Platycarya strobilacea Sieb. et Zucc is a well-known traditional medicine in China, Japan and Korea. The infructescence of P. strobilacea Sieb. et Zucc is a rich source of ellagitannins that are composed of ellagic acid (EA) and gallic acid, linked to a sugar moiety. The aim of this study was to prepare EA by acid hydrolysis of crude tannins from the infructescence of P. strobilacea Sieb. et Zucc, and establish a new technological processing method for EA. The natural antioxidant EA was prepared by using the water extraction of infructescence of P. strobilacea Sieb. et Zucc, evaporation, condensation, acid hydrolysis and prepared by the process of crystallisation. The yield percentage of EA from crude EA was more than 20% and the purity of the product was more than 98%, as identified by using HPLC. The structure was identified on the basis of spectroscopic analysis and comparison with authentic compound.

Isolation and structure of whiskey polyphenols produced by oxidation of oak wood ellagitannins.

PubMed

Fujieda, Miho; Tanaka, Takashi; Suwa, Yoshihide; Koshimizu, Seiichi; Kouno, Isao

2008-08-27

Three new phenolic compounds named whiskey tannins A and B and carboxyl ellagic acid were isolated from commercial Japanese whiskey, along with gallic acid, ellagic acid, brevifolin carboxylic acid, three galloyl glucoses, a galloyl ester of phenolic glucoside, 2,3-(S)-hexahydroxydiphenoylglucose, and castacrenin B. Whiskey tannins A and B were oxidation products of a major oak wood ellagitannin, castalagin, in which the pyrogallol ring at the glucose C-1 position of castalagin was oxidized to a cyclopentenone moiety. These tannins originated from ellagitannins contained in the oak wood used for barrel production; however, the original oak wood ellagitannins were not detected in the whiskey. To examine whether the whiskey tannins were produced during the charring process of barrel production, pyrolysis products of castalagin were investigated. Dehydrocastalagin and a new phenolcarboxylic acid trislactone having an isocoumarin structure were isolated, along with castacrenin F and ellagic acid. However, whiskey tannins were not detected in the products.

Electron-rich triphenylamine-based sensors for picric acid detection.

PubMed

Chowdhury, Aniket; Mukherjee, Partha Sarathi

2015-04-17

This paper demonstrates the role of solvent in selectivity and sensitivity of a series of electron-rich compounds for the detection of trace amounts of picric acid. Two new electron-rich fluorescent esters (6, 7) containing a triphenylamine backbone as well as their analogous carboxylic acids (8, 9) have been synthesized and characterized. Fluorescent triphenylamine coupled with an ethynyl moiety constitutes π-electron-rich selective and sensitive probes for electron-deficient picric acid (PA). In solution, the high sensitivity of all the sensors toward PA can be attributed to a combined effect of the ground-state charge-transfer complex formation and resonance energy transfer between the sensor and analyte. The acids 8 and 9 also showed enhanced sensitivity for nitroaromatics in the solid state, and their enhanced sensitivity could be attributed to exciton migration due to close proximity of the neighboring acid molecules, as evident from the X-ray diffraction study. The compounds were found to be quite sensitive for the detection of trace amount of nitroaromatics in solution, solid, and contact mode.

Discovery of novel BTK inhibitors with carboxylic acids.

PubMed

Gao, Xiaolei; Wang, James; Liu, Jian; Guiadeen, Deodial; Krikorian, Arto; Boga, Sobhana Babu; Alhassan, Abdul-Basit; Selyutin, Oleg; Yu, Wensheng; Yu, Younong; Anand, Rajan; Liu, Shilan; Yang, Chundao; Wu, Hao; Cai, Jiaqiang; Cooper, Alan; Zhu, Hugh; Maloney, Kevin; Gao, Ying-Duo; Fischmann, Thierry O; Presland, Jeremy; Mansueto, My; Xu, Zangwei; Leccese, Erica; Zhang-Hoover, Jie; Knemeyer, Ian; Garlisi, Charles G; Bays, Nathan; Stivers, Peter; Brandish, Philip E; Hicks, Alexandra; Kim, Ronald; Kozlowski, Joeseph A

2017-03-15

We report the design and synthesis of a series of novel Bruton's Tyrosine Kinase (BTK) inhibitors with a carboxylic acid moiety in the ribose pocket. This series of compounds has demonstrated much improved off-target selectivities including adenosine uptake (AdU) inhibition compared to the piperidine amide series. Optimization of the initial lead compound 4 based on BTK enzyme inhibition, and human peripheral blood mononuclear cell (hPBMC) and human whole blood (hWB) activity led to the discovery of compound 40, with potent BTK inhibition, reduced off target activities, as well as favorable pharmacokinetic profile in both rat and dog. Copyright © 2016 Elsevier Ltd. All rights reserved.

Microtropins A-I: 6'-O-(2″S,3″R)-2″-ethyl-2″,3″-dihydroxybutyrates of aliphatic alcohol β-D-glucopyranosides from the branches of Microtropis japonica.

PubMed

Uemura, Yuka; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki; Takeda, Yoshio; Kawahata, Masatoshi; Yamaguchi, Kentaro

2013-03-01

From the branches of Microtropis japonica (Celastraceae), nine aliphatic glucosides, named microtropins A-I, were isolated. The 6-position of glucose was esterified with (2S,3R)-2-ethyl-2,3-dihydroxybutyric acid. Microtropins A-D contained a rare natured product nitrile functional group in their aglycones. The absolute structures of the (2S,3R)-2-ethyl-2,3-dihydroxybutyric acid moiety and aglycone of microtropin A were determined by an X-ray crystallographic method. Copyright © 2012 Elsevier Ltd. All rights reserved.

Design, Synthesis and in vitro Biochemical Activity of Novel Amino Acid Sulfonohydrazide Inhibitors of MurC.

PubMed

Frlan, Rok; Kovač, Andreja; Blanot, Didier; Gobec, Stanislav; Pečar, Slavko; Obreza, Aleš

2011-06-01

Mur ligases are essential enzymes involved in the cytoplasmic steps of peptidoglycan synthesis which remain attractive, yet unexploited targets. In order to develop new antibacterial agents, we have designed a series of new MurC and MurD inhibitors bearing amino acid sulfonohydrazide moiety. The L-Leu series of this class displayed the highest enzyme inhibition with IC50 in the concentration range between 100 and 500 µM, with L-Thr, L-Pro and L-Ala derivatives being inactive. The most promising compound of the series also expressed weak antibacterial activity against S. aureus with MIC = 128 µg/mL.

Biological detection and tagging using tailorable, reactive, highly fluorescent chemosensors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shepodd, Timothy J.; Zifer, Thomas; McElhanon, James Ross

2006-11-01

This program was focused on the development of a fluorogenic chemosensor family that could tuned for reaction with electrophilic (e.g. chemical species, toxins) and nucleophilic (e.g. proteins and other biological molecules) species. Our chemosensor approach utilized the fluorescent properties of well-known berberine-type alkaloids. In situ chemosensor reaction with a target species transformed two out-of-plane, weakly conjugated, short-wavelength chromophores into one rigid, planar, conjugated, chromophore with strong long wavelength fluorescence (530-560 nm,) and large Stokes shift (100-180 nm). The chemosensor was activated with an isourea group which allowed for reaction with carboxylic acid moieties found in amino acids.

Antiproliferative triterpene saponins from Entada africana.

PubMed

Cioffi, Giuseppina; Dal Piaz, Fabrizio; De Caprariis, Paolo; Sanogo, Rokia; Marzocco, Stefania; Autore, Giuseppina; De Tommasi, Nunziatina

2006-09-01

Nine new ester saponins (1-9) were isolated from the roots of Entada africana. Their structures were elucidated by 1D and 2D NMR experiments including 1D and 2D TOCSY, DQF-COSY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis, and chemical methods. The aglycon moieties were found to be echinocystic acid for compounds 1, 2, 4-6, 8, and 9 and acacic acid for 3 and 7. All isolated compounds were tested for their antiproliferative activity against the J774.A1, HEK-293, and WEHI-164 cell lines. Moderate to high cytotoxic potency was found for almost all compounds tested.

GRL-09510, a Unique P2-Crown-Tetrahydrofuranylurethane -Containing HIV-1 Protease Inhibitor, Maintains Its Favorable Antiviral Activity against Highly-Drug-Resistant HIV-1 Variants in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amano, Masayuki; Miguel Salcedo-Gómez, Pedro; Yedidi, Ravikiran S.

We report that GRL-09510, a novel HIV-1 protease inhibitor (PI) containing a newly-generated P2-crown-tetrahydrofuranylurethane (Crwn-THF), a P2'-methoxybenzene, and a sulfonamide isostere, is highly active against laboratory and primary clinical HIV-1 isolates (EC50: 0.0014–0.0028 μM) with minimal cytotoxicity (CC50: 39.0 μM). Similarly, GRL-09510 efficiently blocked the replication of HIV-1NL4-3 variants, which were capable of propagating at high-concentrations of atazanavir, lopinavir, and amprenavir (APV). GRL-09510 was also potent against multi-drug-resistant clinical HIV-1 variants and HIV-2ROD. Under the selection condition, where HIV-1NL4-3 rapidly acquired significant resistance to APV, an integrase inhibitor raltegravir, and a GRL-09510 congener (GRL-09610), no variants highly resistant against GRL-09510more » emerged over long-term in vitro passage of the virus. Crystallographic analysis demonstrated that the Crwn-THF moiety of GRL-09510 forms strong hydrogen-bond-interactions with HIV-1 protease (PR) active-site amino acids and is bulkier with a larger contact surface, making greater van der Waals contacts with PR than the bis-THF moiety of darunavir. The present data demonstrate that GRL-09510 has favorable features for treating patients infected with wild-type and/or multi-drug-resistant HIV-1 variants, that the newly generated P2-Crwn-THF moiety confers highly desirable anti-HIV-1 potency. The use of the novel Crwn-THF moiety sheds lights in the design of novel PIs.« less

NO3- anions can act as Lewis acid in the solid state

NASA Astrophysics Data System (ADS)

Bauzá, Antonio; Frontera, Antonio; Mooibroek, Tiddo J.

2017-02-01

Identifying electron donating and accepting moieties is crucial to understanding molecular aggregation, which is of pivotal significance to biology. Anions such as NO3- are typical electron donors. However, computations predict that the charge distribution of NO3- is anisotropic and minimal on nitrogen. Here we show that when the nitrate's charge is sufficiently dampened by resonating over a larger area, a Lewis acidic site emerges on nitrogen that can interact favourably with electron rich partners. Surveys of the Cambridge Structural Database and Protein Data Bank reveal geometric preferences of some oxygen and sulfur containing entities around a nitrate anion that are consistent with this `π-hole bonding' geometry. Computations reveal donor-acceptor orbital interactions that confirm the counterintuitive Lewis π-acidity of nitrate.

An alternative method to remove PEO-PPO-PEO template in organic-inorganic mesoporous nanocomposites by sulfuric acid extraction

NASA Astrophysics Data System (ADS)

Zhuang, Xin; Qian, Xufang; Lv, Jiahui; Wan, Ying

2010-06-01

Sulfuric acid is used as an extraction agent to remove PEO-PPO-PEO templates in the organic-inorganic mesoporous nanocomposites from the triconstituent co-assembly which includes the low-polymerized phenolic resins, TEOS and triblock copolymer F127. The XRD and TEM results show well ordered mesostructure after extraction with sulfuric acid. As followed from the N 2 sorption isotherms the extracted composites possess high surface areas (332-367 m 2/g), large pore volumes (0.66-0.78 cm 3/g), and large pore sizes (about 10.7 nm). The FT-IR analysis reveals almost complete elimination of triblock copolymer F127, and the maintenance of organic groups. This method shows potentials in removing templates from nanocomposites containing functional moieties.

Pectin functionalised by fatty acids: Diffuse reflectance infrared Fourier transform (DRIFT) spectroscopic characterisation

NASA Astrophysics Data System (ADS)

Kamnev, Alexander A.; Calce, Enrica; Tarantilis, Petros A.; Tugarova, Anna V.; De Luca, Stefania

2015-01-01

Chemically modified pectin derivatives obtained by partial esterification of its hydroxyl moieties with fatty acids (FA; oleic, linoleic and palmitic acids), as well as the initial apple peel pectin were comparatively characterised using diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy. Characteristic changes observed in DRIFT spectra in going from pectin to its FA esters are related to the corresponding chemical modifications. Comparing the DRIFT spectra with some reported data on FTIR spectra of the same materials measured in KBr or NaCl matrices has revealed noticeable shifts of several polar functional groups both in pectin and in its FA-esterified products induced by the halide salts. The results obtained have implications for careful structural analyses of biopolymers with hydrophilic functional groups by means of different FTIR spectroscopic methodologies.

Inhibitors of HIV-1 maturation: Development of structure-activity relationship for C-28 amides based on C-3 benzoic acid-modified triterpenoids.

PubMed

Swidorski, Jacob J; Liu, Zheng; Sit, Sing-Yuen; Chen, Jie; Chen, Yan; Sin, Ny; Venables, Brian L; Parker, Dawn D; Nowicka-Sans, Beata; Terry, Brian J; Protack, Tricia; Rahematpura, Sandhya; Hanumegowda, Umesh; Jenkins, Susan; Krystal, Mark; Dicker, Ira B; Meanwell, Nicholas A; Regueiro-Ren, Alicia

2016-04-15

We have recently reported on the discovery of a C-3 benzoic acid (1) as a suitable replacement for the dimethyl succinate side chain of bevirimat (2), an HIV-1 maturation inhibitor that reached Phase II clinical trials before being discontinued. Recent SAR studies aimed at improving the antiviral properties of 2 have shown that the benzoic acid moiety conferred topographical constraint to the pharmacophore and was associated with a lower shift in potency in the presence of human serum albumin. In this manuscript, we describe efforts to improve the polymorphic coverage of the C-3 benzoic acid chemotype through modifications at the C-28 position of the triterpenoid core. The dimethylaminoethyl amides 17 and 23 delivered improved potency toward bevirimat-resistant viruses while increasing C24 in rat oral PK studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine as orally-active adhesion molecule inhibitors.

PubMed

Kaneko, Toshihiko; Clark, Richard S J; Ohi, Norihito; Ozaki, Fumihiro; Kawahara, Tetsuya; Kamada, Atsushi; Okano, Kazuo; Yokohama, Hiromitsu; Ohkuro, Masayoshi; Muramoto, Kenzo; Takenaka, Osamu; Kobayashi, Seiichi

2004-06-01

Novel piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine were prepared and evaluated for their inhibitory activity on the upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). Replacement of the methanesulfonyl group on the piperidine ring of previously prepared derivatives with a carboxylic acid-containing moiety resulted in a number of potent adhesion molecule inhibitors. Of these, (anti) [3-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)methyl-3-azabicyclo[3.3.1]non-9-yl]acetic acid 2q (ER-49890), showed the most potent oral inhibitory activities against neutrophil migration in an interleukin-1 (IL-1) induced paw inflammation model using mice, and leukocyte accumulation in a carrageenan pleurisy model in the rat, and therapeutic effect on collagen-induced arthritis in rats.

HPLC-UV-ESI-MS analysis of phenolic compounds and antioxidant properties of Hypericum undulatum shoot cultures and wild-growing plants.

PubMed

Rainha, Nuno; Koci, Kamila; Coelho, Ana Varela; Lima, Elisabete; Baptista, José; Fernandes-Ferreira, Manuel

2013-02-01

LC-UV and LC-MS analysis were used to study the phenolic composition of water extracts of Hypericum undulatum (HU) shoot cultures and wild-growing (WG) plants. Total phenolic content (TPC), determined using the Folin-Ciocalteu assay, and the antioxidant activity measured by two complementary methods were also performed for each sample. Mass spectrometry revealed several phenolics acids with quinic acid moieties, flavonols, mostly quercetin, luteolin and apigenin glycosides, flavan-3-ols (catechin and epicatechin) and the xanthonoid mangiferin. Differences in phenolic composition profile and TPC were found between the samples. The major phenolic in HU culture-growing (CG) samples is chlorogenic acid, followed by epicatechin, quercitrin and isoquercitrin. The WG plants presents hyperoside as the main phenolic, followed by isoquercitrin, chlorogenic acid and quercetin. The TPC and antioxidant activity were higher in samples from WG plants. Copyright © 2012 Elsevier Ltd. All rights reserved.

Poly(ionic liquid) based chemosensors for detection of basic amino acids in aqueous medium

NASA Astrophysics Data System (ADS)

Li, Xinjuan; Wang, Kai; Ma, Nana; Jia, Xianbin

2017-09-01

Naked-eye detection of amino acids in water is of great significance in the field of bio-analytical applications. Herein, polymerized ionic liquids (PILs) with controlled chain length structures were synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization and post-quaternization approach. The amino acids recognition performance of PILs with different alkyl chain lengths and molecular weights was evaluated by naked-eye color change and ultraviolet-visible (UV-vis) spectral studies. These PILs were successfully used for highly sensitive and selective detection of Arg, Lys and His in water. The recognition performance was improved effectively with increased molecular weight of PILs. The biosensitivity of the PILs in water was strongly dependent on their aggregation effect and polarization effect. Highly sensitive and selective detection of amino acids was successfully accomplished by introducing positively charged pyridinium moieties and controlled RAFT radical polymerization.

Stimulation by unsaturated fatty acid of squalene uptake in rat liver microsomes.

PubMed

Chin, J; Bloch, K

1985-07-01

Supernatant protein factor (SPF) and anionic phospholipids such as phosphatidylglycerol (PG) stimulate squalene epoxidase activity in rat liver microsomes by promoting [3H]squalene uptake as well as substrate translocation (Chin, J., and K. Bloch. 1984. J. Biol. Chem. 259: 11735-11738). This process is postulated to be membrane-mediated and not carrier-mediated. Here we show that treatment of PG with phospholipase A2 in the presence of bovine serum albumin abolishes the stimulatory effect of SPF on epoxidase activity. Disaturated fatty acyl-PGs are not as effective as egg yolk lecithin PG in the SPF effect. These findings suggest an important role for the unsaturated fatty acid moiety of PG. We also show that at submicellar concentrations, cis-unsaturated fatty acids stimulate microsomal epoxidase activity whereas saturated fatty acids do not. This effect is due to an increase in substrate uptake which in turn may facilitate substrate availability to the enzyme.

An additional role for the Brønsted acid-base catalysts of mandelate racemase in transition state stabilization.

PubMed

Nagar, Mitesh; Bearne, Stephen L

2015-11-10

Mandelate racemase (MR) catalyzes the interconversion of the enantiomers of mandelate and serves as a paradigm for understanding the enzyme-catalyzed abstraction of an α-proton from a carbon acid substrate with a high pKa. The enzyme utilizes a two-base mechanism with Lys 166 and His 297 acting as Brønsted acid and base catalysts, respectively, in the R → S reaction direction. In the S → R reaction direction, their roles are reversed. Using isothermal titration calorimetry (ITC), MR is shown to bind the intermediate/transition state (TS) analogue inhibitor benzohydroxamate (BzH) in an entropy-driven process with a value of ΔCp equal to -358 ± 3 cal mol(-1) K(-1), consistent with an increased number of hydrophobic interactions. However, MR binds BzH with an affinity that is ∼2 orders of magnitude greater than that predicted solely on the basis of hydrophobic interactions [St. Maurice, M., and Bearne, S. L. (2004) Biochemistry 43, 2524], suggesting that additional specific interactions contribute to binding. To test the hypothesis that cation-π/NH-π interactions between the side chains of Lys 166 and His 297 and the aromatic ring and/or the hydroxamate/hydroximate moiety of BzH contribute to the binding of BzH, site-directed mutagenesis was used to generate the MR variants K166M, K166C, H297N, and K166M/H297N and their binding affinity for various ligands determined using ITC. Comparison of the binding affinities of these MR variants with the intermediate/TS analogues BzH and cyclohexanecarbohydroxamate revealed that cation-π/NH-π interactions between His 297 and the hydroxamate/hydroximate moiety and the phenyl ring of BzH contribute approximately 0.26 and 0.91 kcal/mol to binding, respectively, while interactions with Lys 166 contribute approximately 1.74 and 1.74 kcal/mol, respectively. Similarly, comparison of the binding affinities of these mutants with substrate analogues revealed that Lys 166 contributes >2.93 kcal/mol to the binding of (R)-atrolactate, and His 297 contributes 2.46 kcal/mol to the binding of (S)-atrolactate. These results are consistent with Lys 166 and His 297 playing dual roles in catalysis: they act as Brønsted acid-base catalysts, and they stabilize both the enolate moiety and phenyl ring of the altered substrate in the TS.

Concurrent Automated Sequencing of the Glycan and Peptide Portions of O-Linked Glycopeptide Anions by Ultraviolet Photodissociation Mass Spectrometry

PubMed Central

Madsen, James A.; Ko, Byoung Joon; Xu, Hua; Iwashkiw, Jeremy A.; Robotham, Scott A.; Shaw, Jared B.; Feldman, Mario F.; Brodbelt, Jennifer S.

2013-01-01

O -glycopeptides are often acidic owing to the frequent occurrence of acidic saccharides in the glycan, rendering traditional proteomic workflows that rely on positive mode tandem mass spectrometry (MS/MS) less effective. In this report, we demonstrate the utility of negative mode ultraviolet photodissociation (UVPD) MS for the characterization of acidic O-linked glycopeptide anions. This method was evaluated for a series of singly- and multiply-deprotonated glycopeptides from the model glycoprotein kappa casein, resulting in production of both peptide and glycan product ions that afforded 100% sequence coverage of the peptide and glycan moieties from a single MS/MS event. The most abundant and frequent peptide sequence ions were a/x-type products, which, importantly, were found to retain the labile glycan modifications. The glycan-specific ions mainly arose from glycosidic bond cleavages (B, Y, C, and Z ions) in addition to some less common cross-ring cleavages. Based on the UVPD fragmentation patterns, an automated database searching strategy (based on the MassMatrix algorithm) was designed that is specific for the analysis of glycopeptide anions by UVPD. This algorithm was used to identify glycopeptides from mixtures of glycosylated and non-glycosylated peptides, sequence both glycan and peptide moieties simultaneously, and pinpoint the correct site(s) of glycosylation. This methodology was applied to uncover novel site-specificity of the O-linked glycosylated OmpA/MotB from the “superbug” A. baumannii to help aid in the elucidation of the functional role that protein glycosylation plays in pathogenesis. PMID:24006841

Hydrotropic polymer micelles containing acrylic acid moieties for oral delivery of paclitaxel

PubMed Central

Kim, Sungwon; Kim, Ji Young; Huh, Kang Moo; Acharya, Ghanshyam; Park, Kinam

2008-01-01

Hydrotropic polymers (HPs) and their micelles have been recently developed as vehicles for delivery of poorly water-soluble drugs, such as paclitaxel (PTX), by oral administration. The release of PTX from HP micelles, however, was slow and it took more than a day for complete release of the loaded PTX. Since the gastrointestinal (GI) transit time is known to be only several hours, pH-sensitive HP micelles were prepared for fast release of the loaded PTX responding to pH changes along the GI tract. Acrylic acid (AA) was introduced, as a release modulator, into HPs by copolymerization with 4-(2-vinylbenzyloxy)-N,N-(diethylnicotinamide) (VBODENA). The AA content was varied from 0% to 50 % (in the molar ratio to VBODENA). HPs spontaneously produced micelles in water, and their critical micelle concentrations (CMCs) ranged from 31 μg/mL to 86 μg/mL. Fluorescence probe study using pyrene showed that blank HP micelles possessed a good pH-sensitivity, which was clearly observed at relatively high AA contents and pH > 6. The pH sensitivity also affected the PTX loading property. Above pH 5, the PTX loading content and loading efficiency in HP micelles were significantly reduced. Although this may be primarily due to the AA moieties, other factors may include PTX degradation and polymer aggregation. The PTX release from HP micelles with more than 20% (mol) AA contents was completed within 12 h in a simulated intestinal fluid (SIF, pH=6.5). The HP micelles without any AA moiety showed very slow release profiles. In the simulated gastric fluid (SGF, pH=1.6), severe degradation of the released PTX was observed. The pH-dependent release of PTX from HP micelles can be used to increase the bioavailability of PTX upon oral delivery. PMID:18672013

Structural elucidation of main ozonation products of the artificial sweeteners cyclamate and acesulfame.

PubMed

Scheurer, Marco; Godejohann, Markus; Wick, Arne; Happel, Oliver; Ternes, Thomas A; Brauch, Heinz-Jürgen; Ruck, Wolfgang K L; Lange, Frank Thomas

2012-05-01

The two artificial sweeteners cyclamate (CYC) and acesulfame (ACE) have been detected in wastewater and drinking water treatment plants. As in both facilities ozonation might be applied, it is important to find out if undesired oxidation products (OPs) are formed. For the separation and detection of the OPs, several analytical techniques, including nuclear magnetic resonance experiments, were applied. In order to distinguish between direct ozone reaction and a radical mechanism, experiments were carried out at different pH values with and without scavenging OH radicals. Kinetic experiments were used for confirmation that the OPs are formed during short ozone contact time applied in waterworks. Samples from a waterworks using bank filtrate as raw water were analyzed in order to prove that the identified OPs are formed in real and full-scale ozone applications. In the case of CYC, oxidation mainly occurs at the carbon atom, where the sulfonamide moiety is bound to the cyclohexyl ring. Consequently, amidosulfonic acid and cyclohexanone are formed as main OPs of CYC. When ozone reacts at another carbon atom of the ring a keto moiety is introduced into the CYC molecule. Acetic acid and the product ACE OP170, an anionic compound with m/z=170 and an aldehyde hydrate moiety, were identified as the main OPs for ACE. The observed reaction products suggest an ozone reaction according to the Criegee mechanism due to the presence of a C=C double bond. ACE OP170 was also detected after the ozonation unit of a full-scale drinking water treatment plant which uses surface water-influenced bank filtrate as raw water. Acesulfame can be expected to be found in anthropogenic-influenced raw water used for drinking water production. However, when ACE OP170 is formed during ozonation, it is not expected to cause any problem for drinking water suppliers, because the primary findings suggest its removal in subsequent treatment steps, such as activated carbon filters.

Complexes of the antimicrobial ciprofloxacin with soil, peat, and aquatic humic substances.

PubMed

Aristilde, Ludmilla; Sposito, Garrison

2013-07-01

Natural organic matter (NOM) is implicated in the binding of antibiotics by particles in soils and waters. The authors' previous computational study revealed structural rearrangement of both hydrophilic and hydrophobic moieties of NOM to favor H-bonding and other intermolecular interactions, as well as both competition with ion-exchange reactions and bridging interactions by NOM-bound divalent cations. The importance of these interactions was investigated using fluorescence-quenching spectroscopy to study the adsorption of ciprofloxacin (Cipro), a fluoroquinolone antibiotic, on 4 reference humic substances (HSs): Elliott soil humic acid (HA), Pahokee peat HA, and Suwannee river HA and fulvic acid. A simple affinity spectrum HS model was developed to characterize the cation-exchange capacity and the amount of H-bond donor moieties as a function of pH. The adsorption results stress the influence of both pH conditions and the type of HS: both soil HA and peat HA exhibited up to 3 times higher sorption capacity than the aquatic HS at pH ≥ 6, normalizing to the aromatic C content accounted for the differences among the terrestrial HS, and increasing the concentration of divalent cations led to a decrease in adsorption on aquatic HA but not on soil HA. In addition, the pH-dependent speciation models of the Cipro-HS complexes illustrate an increase in complexation due to an increase in deprotonation of HS ligands with increasing pH and, at circumneutral and alkaline pH, enhanced complexation of zwitterionic Cipro only in the presence of soil HA and peat HA. The findings of the present study imply that, in addition to electrostatic interactions, van der Waals interactions as facilitated by aromatic structures and H-bond donating moieties in terrestrial HS may facilitate a favorable binding environment. Environ Toxicol Chem 2013;32:1467-1478. © 2013 SETAC. Copyright © 2013 SETAC.

Investigation of acyl migration in mono- and dicaffeoylquinic acids under aqueous basic, aqueous acidic, and dry roasting conditions.

PubMed

Deshpande, Sagar; Jaiswal, Rakesh; Matei, Marius Febi; Kuhnert, Nikolai

2014-09-17

Acyl migration in chlorogenic acids describes the process of migration of cinnamoyl moieties from one quinic acid alcohol group to another, thus interconverting chlorogenic acid regioisomers. It therefore constitutes a special case of transesterification reaction. Acyl migration constitutes an important reaction pathway in both coffee roasting and brewing, altering the structure of chlorogenic acid initially present in the green coffee bean. In this contribution we describe detailed and comprehensive mechanistic studies comparing inter- and intramolecular acyl migration involving the seven most common chlorogenic acids in coffee. We employe aqueous acidic and basic conditions mimicking the brewing of coffee along with dry roasting conditions. We show that under aqueous basic conditions intramolecular acyl migration is fully reversible with basic hydrolysis competing with acyl migration. 3-Caffeoylquinic acid was shown to be most labile to basic hydrolysis. We additionally show that the acyl migration process is strongly pH dependent with increased transesterification taking place at basic pH. Under dry roasting conditions acyl migration competes with dehydration to form lactones. We argue that acyl migration precedes lactonization, with 3-caffeoylquinic acid lactone being the predominant product.

In situ synthesis of twelve dialkyltartrate-boric acid complexes and two polyols-boric acid complexes and their applications as chiral ion-pair selectors in nonaqueous capillary electrophoresis.

PubMed

Wang, Li-Juan; Yang, Juan; Yang, Geng-Liang; Chen, Xing-Guo

2012-07-27

In this paper, twelve dialkyltartrate-boric acid complexes and two polyols-boric acid complexes were in situ synthesized by the reaction of different dialkyltartrates or polyols with boric acid in methanol containing triethylamine. All of the twelve dialkyltartrate-boric acid complexes were found to have relatively good chiral separation performance in nonaqueous capillary electrophoresis (NACE). Their chiral recognition effects in terms of both enantioselectivity (α) and resolution (R(s)) were similar when the number of carbon atoms was below six in the alkyl group of alcohol moiety. The dialkyltartrates containing alkyl groups of different structures but the same number of carbon atoms, i.e. one of straight chain and one of branched chain, also provided similar chiral recognition effects. Furthermore, it was demonstrated for the first time that two methanol insoluble polyols, D-mannitol and D-sorbitol, could react with boric acid to prepare chiral ion-pair selectors using methanol as the solvent medium. Copyright © 2012 Elsevier B.V. All rights reserved.

4-O-Acetyl-sialic acid (Neu4,5Ac2) in acidic milk oligosaccharides of the platypus (Ornithorhynchus anatinus) and its evolutionary significance.

PubMed

Urashima, Tadasu; Inamori, Hiroaki; Fukuda, Kenji; Saito, Tadao; Messer, Michael; Oftedal, Olav T

2015-06-01

Monotremes (echidnas and platypus) retain an ancestral form of reproduction: egg-laying followed by secretion of milk onto skin and hair in a mammary patch, in the absence of nipples. Offspring are highly immature at hatching and depend on oligosaccharide-rich milk for many months. The primary saccharide in long-beaked echidna milk is an acidic trisaccharide Neu4,5Ac2(α2-3)Gal(β1-4)Glc (4-O-acetyl 3'-sialyllactose), but acidic oligosaccharides have not been characterized in platypus milk. In this study, acidic oligosaccharides purified from the carbohydrate fraction of platypus milk were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and (1)H-nuclear magnetic resonance spectroscopy. All identified structures, except Neu5Ac(α2-3)Gal(β1-4)Glc (3'-sialyllactose) contained Neu4,5Ac2 (4-O-acetyl-sialic acid). These include the trisaccharide 4-O-acetyl 3'-sialyllactose, the pentasaccharide Neu4,5Ac2(α2-3)Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)Glc (4-O-acetyl-3'-sialyllacto-N-tetraose d) and the hexasaccharide Neu4,5Ac2(α2-3)Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-3)Gal(β1-4)Glc (4-O-acetyl-3'-sialyllacto-N-fucopentaose III). At least seven different octa- to deca-oligosaccharides each contained a lacto-N-neohexaose core (LNnH) and one or two Neu4,5Ac2 and one to three fucose residues. We conclude that platypus milk contains a diverse (≥ 20) array of neutral and acidic oligosaccharides based primarily on lactose, lacto-N-neotetraose (LNnT) and LNnH structural cores and shares with echidna milk the unique feature that all identified acidic oligosaccharides (other than 3'-sialyllactose) contain the 4-O-acetyl-sialic acid moiety. We propose that 4-O-acetylation of sialic acid moieties protects acidic milk oligosaccharides secreted onto integumental surfaces from bacterial hydrolysis via steric interference with bacterial sialidases. This may be of evolutionary significance since taxa ancestral to monotremes and other mammals are thought to have secreted milk, or a milk-like fluid containing oligosaccharides, onto skin surfaces. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Structure of suicide-inactivated. beta. -hydroxydecanoyl-thioester dehydrase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwab, J.M.; Ho, C.K.; Li, W.B.

..beta..-Hydroxydecanoylthioester dehydrase, the key enzyme in biosynthesis of unsaturated fatty acids under anaerobic conditions, equilibrates thioesters of (R)-3-hydroxydecanoic acid, E-2-decenoic acid, and Z-3-decenoic acid. Dehydrase is irreversibly inactivated by the N-acetylcysteamine thioester of 3-decynoic acid (3-decynoyl-NAC), via dehydrase-catalyzed isomerization to 2,3-decadienoyl-NAC. To probe the relationship between normal catalysis and suicide inactivation, the structure of the inactivated enzyme has been studied. 3-(2-/sup 13/C)Decynoyl-NAC was synthesized and incubated with dehydrase. /sup 13/C NMR showed that attack of 2,3-decadienoyl-NAC by the active site histidine gives 3-histidinyl-3-decenoyl-NAC, which slowly rearranges to the more stable ..delta../sup 2/ isomer. Model histidine-allene adducts have been made andmore » characterized. Analysis of NMR data show that the C=C configuration of the decenoyl moiety of enzyme-bound inactivator is E. The suggestion that the mechanism of dehydrase inactivation parallels its normal mechanism of action is supported these findings.« less

Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids.

PubMed

Borgström, Björn; Huang, Xiaoli; Chygorin, Eduard; Oredsson, Stina; Strand, Daniel

2016-06-09

The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N- and O-alkylation are presented. The parent hydroxamic acid, salinomycin-NHOH, forms both inclusion complexes and well-defined electroneutral complexes with potassium and sodium cations via 1,3-coordination by the hydroxamic acid moiety to the metal ion. A crystal structure of an cationic sodium complex with a noncoordinating anion corroborates this finding and, moreover, reveals a novel type of hydrogen bond network that stabilizes the head-to-tail conformation that encapsulates the cation analogously to the native structure. The hydroxamic acid derivatives display down to single digit micromolar activity against cancer cells but unlike salinomycin selective reduction of ALDH(+) cells, a phenotype associated with cancer stem cells was not observed. Mechanistic implications are discussed.

Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids

PubMed Central

2016-01-01

The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N- and O-alkylation are presented. The parent hydroxamic acid, salinomycin-NHOH, forms both inclusion complexes and well-defined electroneutral complexes with potassium and sodium cations via 1,3-coordination by the hydroxamic acid moiety to the metal ion. A crystal structure of an cationic sodium complex with a noncoordinating anion corroborates this finding and, moreover, reveals a novel type of hydrogen bond network that stabilizes the head-to-tail conformation that encapsulates the cation analogously to the native structure. The hydroxamic acid derivatives display down to single digit micromolar activity against cancer cells but unlike salinomycin selective reduction of ALDH+ cells, a phenotype associated with cancer stem cells was not observed. Mechanistic implications are discussed. PMID:27326340

Screening for Triterpenoid Saponins in Plants Using Hyphenated Analytical Platforms.

PubMed

Khakimov, Bekzod; Tseng, Li Hong; Godejohann, Markus; Bak, Søren; Engelsen, Søren Balling

2016-11-24

Recently the number of studies investigating triterpenoid saponins has drastically increased due to their diverse and potentially attractive biological activities. Currently the literature contains chemical structures of few hundreds of triterpenoid saponins of plant and animal origin. Triterpenoid saponins consist of a triterpene aglycone with one or more sugar moieties attached to it. However, due to similar physico-chemical properties, isolation and identification of a large diversity of triterpenoid saponins remain challenging. This study demonstrates a methodology to screen saponins using hyphenated analytical platforms, GC-MS, LC-MS/MS, and LC-SPE-NMR/MS, in the example of two different phenotypes of the model plant Barbarea vulgaris (winter cress), glabrous (G) and pubescent (P) type that are known to differ by their insect resistance. The proposed methodology allows for detailed comparison of saponin profiles from intact plant extracts as well as saponin aglycone profiles from hydrolysed samples. Continuously measured 1D proton NMR data during LC separation along with mass spectrometry data revealed significant differences, including contents of saponins, types of aglycones and numbers of sugar moieties attached to the aglycone. A total of 49 peaks were tentatively identified as saponins from both plants; they are derived from eight types of aglycones and with 2-5 sugar moieties. Identification of two previously known insect-deterrent saponins, hederagenin cellobioside and oleanolic acid cellobioside, demonstrated the applicability of the methodology for relatively rapid screening of bioactive compounds.

[Analysis of constituents of ester-type gum bases used as natural food additives].

PubMed

Tada, Atsuko; Masuda, Aino; Sugimoto, Naoki; Yamagata, Kazuo; Yamazaki, Takeshi; Tanamoto, Kenichi

2007-12-01

The differences in the constituents of ten ester-type gum bases used as natural food additives in Japan (urushi wax, carnauba wax, candelilla wax, rice bran wax, shellac wax, jojoba wax, bees wax, Japan wax, montan wax, and lanolin) were investigated. Several kinds of gum bases showed characteristic TLC patterns of lipids. In addition, compositions of fatty acid and alcohol moieties of esters in the gum bases were analyzed by GC/MS after methanolysis and hydrolysis, respectively. The results indicated that the varieties of fatty acids and alcohols and their compositions were characteristic for each gum base. These results will be useful for identification and discrimination of the ester-type gum bases.

Diastereoselective preparation of (R)- and (S)-2-methoxy-2-phenylpent-3-ynoic acids and their use as reliable chiral derivatizing agents.

PubMed

Pérez-Estrada, Salvador; Joseph-Nathan, Pedro; Jiménez-Vázquez, Hugo A; Medina-López, Manuel E; Ayala-Mata, Francisco; Zepeda, L Gerardo

2012-02-17

Benzoyl-S,O-acetals 1a and 1b were used as chiral auxiliaries to achieve the diastereoselective preparation of both enantiomers of 2-methoxy-2-phenylpent-3-ynoic acids (MPPAs). The latter were condensed with several chiral secondary alcohols and some primary amines to evaluate their potential as chiral derivatizing agents (CDAs). The (1)H NMR spectra of the corresponding esters and amides showed strong consistency with the absolute configuration of the carbinol and amine moieties, whose observed ΔδL(1) and ΔδL(2) values were in the ranges of 0.1-0.4 and 0.02-0.12 ppm, respectively.

Characterization of radiation damage to DNA by reaction with borohydride.

PubMed Central

Schellenberg, K A; Shaeffer, J; Nichols, R K; Gates, D

1981-01-01

Irradiation of aqueous solutions of native calf thymus DNA with x-rays produced functional groups that reacted with sodium borohydride. The DNA was labeled with tritium from NaB3H4 to the extent of 2.0 x 10(-10) atom/dalton/rad. The presence of cysteamine or other radical scavengers, or saturation of the solution with nitrogen during irradiation decreased the labeling. After mild acid hydrolysis, the major tritium-containing moiety was identical with 2,3-dihydroxy-2-methylpropanoic acid in all chromatographic systems tested. The suggested mechanism of labeling involved reduction by borohydride of the potential aldehyde at carbon 6 of thymine glycol residues present in the irradiated DNA. PMID:7279674

Synthesis of novel 2-cyano substituted glycyrrhetinic acid derivatives as inhibitors of cancer cells growth and NO production in LPS-activated J-774 cells.

PubMed

Salomatina, Oksana V; Markov, Andrey V; Logashenko, Evgeniya B; Korchagina, Dina V; Zenkova, Marina A; Salakhutdinov, Nariman F; Vlassov, Valentin V; Tolstikov, Genrikh A

2014-01-01

Here we report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring glycyrrhetinic acid bearing a 2-cyano-3-oxo-1-en moiety in the A-ring and double bonds and carbonyl groups in the C, D and E rings. Bioassays using murine macrophage-like and tumor cells show that compound 4, which differs from Soloxolone methyl by the absence of a 9(11)-double bond in the C-ring, displays anti-inflammatory and inhibitory activities with respect to tumor cells with a high selectivity index value. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis and characterization of a poly(lactic-co-glycolic acid) core + poly(N-isopropylacrylamide) shell nanoparticle system

PubMed Central

Kosinski, Aaron M.; Brugnano, Jamie L.; Seal, Brandon L.; Knight, Frances C.; Panitch, Alyssa

2012-01-01

Poly(lactic-co-glycolic acid) (PLGA) is a popular material used to prepare nanoparticles for drug delivery. However, PLGA nanoparticles lack desirable attributes including active targeting abilities, resistance to aggregation during lyophilization, and the ability to respond to dynamic environmental stimuli. To overcome these issues, we fabricated a nanoparticle consisting of a PLGA core encapsulated within a shell of poly(N-isopropylacrylamide). Dynamic light scattering and transmission electron microscope imaging were used to characterize the nanoparticles, while an MTT assay and ELISA suggested biocompatibility in THP1 cells. Finally, a collagen type II binding assay showed successful modification of these nanoparticles with an active targeting moiety. PMID:23507885

A mitochondria-targeted turn-on fluorescent probe for the detection of glutathione in living cells.

PubMed

Zhang, Jian; Bao, Xiaolong; Zhou, Junliang; Peng, Fangfang; Ren, Hang; Dong, Xiaochun; Zhao, Weili

2016-11-15

A novel turn-on red fluorescent BODIPY-based probe (Probe 1) for the detection of glutathione was developed. Such a probe carries a para-dinitrophenoxy benzyl pyridinium moiety at the meso position of a BODIPY dye as self-immolative linker. Probe 1 responds selectively to glutathione with the detection limit of 109nM over other amino acids, common metal ions, reactive oxygen species, reactive nitrogen species, and reactive sulfur species. A novel electrostatic interaction to modulate the SNAr attack of glutathione was believed to play significant role for the observed selective response to glutathione. The cleavage of dinitrophenyl ether by glutathione leads to the production of para-hydroxybenzyl moiety which is able to self-immolate through an intramolecular 1,4-elimination reaction to release the fluorescent BODIPY dye. The low toxic probe has been successfully used to detect mitochondrial glutathione in living cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel α,β-unsaturated amide derivatives bearing α-amino phosphonate moiety as potential antiviral agents.

PubMed

Lan, Xianmin; Xie, Dandan; Yin, Limin; Wang, Zhenzhen; Chen, Jin; Zhang, Awei; Song, Baoan; Hu, Deyu

2017-09-15

Based on flexible construction and broad bioactivity of ferulic acid, a series of novel α,β-unsaturated amide derivatives bearing α-aminophosphonate moiety were designed, synthesized and systematically evaluated for their antiviral activity. Bioassay results indicated that some compounds exhibited good antiviral activities against cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV) in vivo. Especially, compound g18 showed excellent curative and protective activities against CMV, with half-maximal effective concentration (EC 50 ) values of 284.67μg/mL and 216.30μg/mL, which were obviously superior to that of Ningnanmycin (352.08μg/mL and 262.53μg/mL). Preliminary structure-activity relationships (SARs) analysis revealed that the introduction of electron-withdrawing group at the 2-position or 4-position of the aromatic ring is favorable for antiviral activity. Present work provides a promising template for development of potential inhibitor of plant virus. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical preservation of insect cuticle from the Pleistocene asphalt deposits of California, USA

NASA Astrophysics Data System (ADS)

Stankiewicz, B. Artur; Briggs, Derek E. G.; Evershed, Richard P.; Duncan, Ian J.

1997-06-01

Cuticles of Coleoptera (beetles) and Orthoptera (crickets) from the Pleistocene asphalt deposits of Rancho La Brea and McKittrick in California, USA were studied by means of flash pyrolysis-gas chromatography /mass spectrometry (py-GC/MS). Commercial chitin, amino acid standards, and fresh and decayed cuticles of modern beetle and cricket were likewise investigated to allow the state of preservation of the fossil specimens to be interpreted. Insect cuticles are composed of chitin and proteins covalently cross-linked via catecholamine moieties. Pyrolysis of the fossil insects yielded all the products normally obtained from the pyrolysis of the chitin biopolymer, indicating that it has survived in a highly intact state. Proteins, on the other hand, are poorly preserved. Only phenols, indoles, and nitrobenzenes were present among the pyrolysis products, providing evidence for the preservation of tyrosine, tryptophan, and phenylalanine moieties. This demonstrates the preferential preservation of chitin in comparison with proteins, a result confirmed by scanning electron microscopy of the structure.

Structure and biological function of ENPP6, a choline-specific glycerophosphodiester-phosphodiesterase

PubMed Central

Morita, Junko; Kano, Kuniyuki; Kato, Kazuki; Takita, Hiroyuki; Sakagami, Hideki; Yamamoto, Yasuo; Mihara, Emiko; Ueda, Hirofumi; Sato, Takanao; Tokuyama, Hidetoshi; Arai, Hiroyuki; Asou, Hiroaki; Takagi, Junichi; Ishitani, Ryuichiro; Nishimasu, Hiroshi; Nureki, Osamu; Aoki, Junken

2016-01-01

Choline is an essential nutrient for all living cells and is produced extracellularly by sequential degradation of phosphatidylcholine (PC). However, little is known about how choline is produced extracellularly. Here, we report that ENPP6, a choline-specific phosphodiesterase, hydrolyzes glycerophosphocholine (GPC), a degradation product of PC, as a physiological substrate and participates in choline metabolism. ENPP6 is highly expressed in liver sinusoidal endothelial cells and developing oligodendrocytes, which actively incorporate choline and synthesize PC. ENPP6-deficient mice exhibited fatty liver and hypomyelination, well known choline-deficient phenotypes. The choline moiety of GPC was incorporated into PC in an ENPP6-dependent manner both in vivo and in vitro. The crystal structure of ENPP6 in complex with phosphocholine revealed that the choline moiety of the phosphocholine is recognized by a choline-binding pocket formed by conserved aromatic and acidic residues. The present study provides the molecular basis for ENPP6-mediated choline metabolism at atomic, cellular and tissue levels. PMID:26888014

New AdoMet Analogues as Tools for Enzymatic Transfer of Photo-Cross-Linkers and Capturing RNA-Protein Interactions.

PubMed

Muttach, Fabian; Mäsing, Florian; Studer, Armido; Rentmeister, Andrea

2017-05-02

Elucidation of biomolecular interactions is of utmost importance in biochemistry. Photo-cross-linking offers the possibility to precisely determine RNA-protein interactions. However, despite the inherent specificity of enzymes, approaches for site-specific introduction of photo-cross-linking moieties into nucleic acids are scarce. Methyltransferases in combination with synthetic analogues of their natural cosubstrate S-adenosyl-l-methionine (AdoMet) allow for the post-synthetic site-specific modification of biomolecules. We report on three novel AdoMet analogues bearing the most widespread photo-cross-linking moieties (aryl azide, diazirine, and benzophenone). We show that these photo-cross-linkers can be enzymatically transferred to the methyltransferase target, that is, the mRNA cap, with high efficiency. Photo-cross-linking of the resulting modified mRNAs with the cap interacting protein eIF4E was successful with aryl azide and diazirine but not benzophenone, reflecting the affinity of the modified 5' caps. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure and dynamics of a salt-bridge model system in water and DMSO

NASA Astrophysics Data System (ADS)

Lotze, S.; Bakker, H. J.

2015-06-01

We study the interaction between the ions methylguanidinium and trifluoroacetate dissolved in D2O and dimethylsulfoxide with linear infrared spectroscopy and femtosecond two-dimensional infrared spectroscopy. These ions constitute model systems for the side chains of arginine and glutamic and aspartic acid that are known to form salt bridges in proteins. We find that the salt-bridge formation of methylguanidinium and trifluoroacetate leads to a significant acceleration of the vibrational relaxation dynamics of the antisymmetric COO stretching vibration of the carboxyl moiety of trifluoroacetate. Salt-bridge formation has little effect on the rate of the spectral fluctuations of the CN stretching vibrations of methylguanidinium. The anisotropy of the cross peaks between the antisymmetric COO stretching vibration of trifluoroacetate and the CN stretching vibrations of methylguanidinium reveals that the salt-bridge is preferentially formed in a bidentate end-on configuration in which the two C=O groups of the carboxylate moiety form strong hydrogen bonds with the two -NH2 groups of methylguanidinium.

Crystal structure of 4,4′-(disulfanediyl)dibutanoic acid–4,4′-bipyridine (1/1)

PubMed Central

Atria, Ana María; Garland, Maria Teresa; Baggio, Ricardo

2014-01-01

4,4′-(Disulfanediyl)dibutanoic acid (dtba) and 4,4′-bipyridine (4,4′-bpy) crystallize in an 1:1 ratio, leading to the title co-crystal with composition C8H14O4S2·C10H8N2. A distinctive feature of the crystal structure is the geometry of the dtba moiety, which appears to be stretched [with a 9.98 (1) Å span between outermost carbons] and acts as an hydrogen-bonding connector, forming linear chains along [-211] with the 4,4′-bpy moiety by way of O—H⋯N hydrogen bonds and C—H⋯O interactions. The influence of the mol­ecular shape on the hydrogen-bonding pattern is analysed by comparing the title compound and two other 4,4′-bpy co-crystals with closely related mol­ecules of similar formulation but different geometry, showing the way in which this correlates with the packing arrangement. PMID:25309167

Using heteroaryl-lithium reagents as hydroxycarbonyl anion equivalents in conjugate addition reactions with (S,S)-(+)-pseudoephedrine as chiral auxiliary; enantioselective synthesis of 3-substituted pyrrolidines.

PubMed

Alonso, Beatriz; Ocejo, Marta; Carrillo, Luisa; Vicario, Jose L; Reyes, Efraim; Uria, Uxue

2013-01-18

We have developed an efficient protocol for carrying out the stereocontrolled formal conjugate addition of hydroxycarbonyl anion equivalents to α,β-unsaturated carboxylic acid derivatives using (S,S)-(+)-pseudoephedrine as chiral auxiliary, making use of the synthetic equivalence between the heteroaryl moieties and the carboxylate group. This protocol has been applied as key step in the enantioselective synthesis of 3-substituted pyrrolidines in which, after removing the chiral auxiliary, the heteroaryl moiety is converted into a carboxylate group followed by reduction and double nucleophilic displacement. Alternatively, the access to the same type of heterocyclic scaffold but with opposite absolute configuration has also been accomplished by making use of the regio- and diastereoselective conjugate addition of organolithium reagents to α,β,γ,δ-unsaturated amides derived from the same chiral auxiliary followed by chiral auxiliary removal, ozonolysis, and reductive amination/intramolecular nucleophilic displacement sequence.

Molecular Organization of Cholesterol in Docosahexaenoate-Rich Lipid Bilayers

NASA Astrophysics Data System (ADS)

Wassall, Stephen R.; Brzustowicz, Michael R.; Cherezov, Vadim; Caffrey, Martin; Zerouga, Mustapha; Stillwell, William

2002-03-01

We investigated the molecular organization of cholesterol in 1,2-didocosahexaenoylphosphatidylcholine (22:6-22:6PC) and 1-stearoyl-2-docosahexaenoylphosphatidylcholine (18:0-22:6PC) bilayers. The solubility of the sterol measured by wide-angle x-ray diffraction was < 20 mol% in 22:6-22:6PC bilayers which contrasts with > 50 mol% in 18:0-22:6PC. Solid state ^2H NMR of [3α-^2H_1]cholesterol suggests that the reduction in solubility correlates with a larger tilt angle α0 = 24^o for the steroid moiety in 22:6-22:6PC bilayers than in 18:0-22:6PC where α0 < 24^o. We attribute the low solubility of cholesterol in 22:6-22:6PC membranes to steric incompatibility between the rigid steroid moiety and the highly polyunsaturated docosahexaenoic acid (DHA) chain, which has the potential to promote lateral heterogeneity within neural membranes rich in DHA and has implications for receptor activation.

Electrochemistry and electron paramagnetic resonance spectroscopy of cytochrome c and its heme-disrupted analogs.

PubMed

Novak, David; Mojovic, Milos; Pavicevic, Aleksandra; Zatloukalova, Martina; Hernychova, Lenka; Bartosik, Martin; Vacek, Jan

2018-02-01

Cytochrome c (cyt c) is one of the most studied conjugated proteins due to its electron-transfer properties and ability to regulate the processes involved in homeostasis or apoptosis. Here we report an electrochemical strategy for investigating the electroactivity of cyt c and its analogs with a disrupted heme moiety, i.e. apocytochrome c (acyt c) and porphyrin cytochrome c (pcyt c). The electrochemical data are supplemented with low-temperature and spin-probe electron paramagnetic resonance (EPR) spectroscopy. The main contribution of this report is a complex evaluation of cyt c reduction and oxidation at the level of surface-localized amino acid residues and the heme moiety in a single electrochemical scan. The electrochemical pattern of cyt c is substantially different to both analogs acyt c and pcyt c, which could be applicable in further studies on the redox properties and structural stability of cytochromes and other hemeproteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel small molecule inhibitors targeting the "switch region" of bacterial RNAP: structure-based optimization of a virtual screening hit.

PubMed

Sahner, J Henning; Groh, Matthias; Negri, Matthias; Haupenthal, Jörg; Hartmann, Rolf W

2013-07-01

Rising resistance against current antibiotics necessitates the development of antibacterial agents with alternative targets. The "switch region" of RNA polymerase (RNAP), addressed by the myxopyronins, could be such a novel target site. Based on a hit candidate discovered by virtual screening, a small library of 5-phenyl-3-ureidothiophene-2-carboxylic acids was synthesized resulting in compounds with increased RNAP inhibition. Hansch analysis revealed π (lipophilicity constant) and σ (Hammet substituent constant) of the substituents at the 5-phenyl moiety to be crucial for activity. The binding mode was proven by the targeted introduction of a moiety mimicking the enecarbamate side chain of myxopyronin into the hit compound, accompanied by enhanced RNAP inhibitory potency. The new compounds displayed good antibacterial activities against Gram positive bacteria and Gram negative Escherichia coli TolC and a reduced resistance frequency compared to the established antibiotic rifampicin. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Augmentation of ferulic acid-induced vasorelaxation with aging and its structure importance in thoracic aorta of spontaneously hypertensive rats.

PubMed

Fukuda, Toshihiko; Kuroda, Takahiro; Kono, Miki; Hyoguchi, Mai; Tanaka, Mitsuru; Matsui, Toshiro

2015-10-01

Aging deteriorates vascular functions such as vascular reactivity and stiffness. Thus far, various reports suggest that bioactive compounds can improve vascular functions. However, few age-related studies of natural bioactive compounds are available. The present study attempted to evaluate age-related vasorelaxation of bioactive cinnamic acids, caffeic acid, and ferulic acid using aged rat thoracic aorta. Vasorelaxation was evaluated in thoracic aorta from both 8, 18, and 40 weeks old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) respectively. The result indicated that caffeic acid possessed the vasorelaxation regardless of aging in WKY and SHR. Moreover, the vasorelaxation of ferulic acid enhanced with aging in SHR. The vasorelaxation behavior was acted in an endothelium-independent manner. To access structure importance of enhanced vasorelaxation, analogues of ferulic acid were tested. In 40 weeks old SHR, 3,4-dimethoxycinnamic acid and coniferyl alcohol exhibited equivalent vasorelaxation activity with ferulic acid, providing the structural importance of methoxy-modified 3-position on the phenyl ring and 2-propenoic moiety. These results firstly demonstrated that enhanced vasorelaxation of ferulic acid with aging and 3,4-dimethoxycinnamic acid and coniferyl alcohol, along with ferulic acid, might exhibit the therapeutic potential of vasoactive power with aging.

Synthetic Lectins: New Tools for Detection and Management of Prostate Cancer

DTIC Science & Technology

2014-08-01

from the SL prior to sequencing. When using MALDI-MS we found that oxidation of the boronic acid, followed by cleavage of the resulting 2- methylphenol...challenging due to the effect of the benzoboroxole moiety on ionization. As such, we are optimizing a variety of oxidation and cross coupling steps that...healthy) 26    reading for each patient sample. Using de -identified patient disease data, LDA analysis was carried out to determine the ability of

High thermal stability and antiferromagnetic properties of a 3D Mn(II)-organic framework with metal carboxylate chains

NASA Astrophysics Data System (ADS)

Han, Lei; Zhou, Yan; Wang, Xiu-Teng; Li, Xing; Tong, Ming-Liang

2009-04-01

A novel three-dimensional metal-organic framework, [Mn 2(hfipbb) 2(bpy)] n ( 1) (H 2hfipbb = 4,4'-(hexafluoroisopropylidene)bis(benzoic acid), bpy = 4,4'-bipyridine), has been hydrothermally synthesized and structurally characterized. The complex consists of metal carboxylate chains, which are cross-linked to six adjacent chains through organic moieties forming extended three-dimensional networks. Complex 1 exhibits high thermal stability (450 °C) and antiferromagnetic properties.

Stress of anesthesia with M.S. 222 and Benzocaine in Rainbow Trout (Salmo gairdneri)

USGS Publications Warehouse

Wedemeyer, Gary

1970-01-01

Rainbow trout (Salmo gairdneri) anesthetized with M.S. 222 for periods up to 12 min experience interrenal ascorbate depletion, uremia, and moderate hypercholesterolemia. Anesthesia with neutralized M.S. 222 (pH 7) or benzocaine prevented these changes and significantly reduced the variability in plasma glucose, cholesterol, and cortisol, indicating that the stress of anesthesia with M.S. 222 is due to the low pK of the sulfonic acid moiety.

Acetylene-Terminated Aromatic Amide Monomers

DTIC Science & Technology

1989-10-01

syntheses. . The diacid with the sulfone moiety (3) (Z=SO,) had been prepared via the action of m- cresol on bis(p-ch-loropheAyl)- sulfone in the presence...from the nitro -displace- ment reaction of 4,4,-dipitrobenzophenone and m-hydroxybenzoic acid in the presence of base. The ready availability of the...aminophenylacetylene (5) (R=m-C-CH) could be purchased from a commercial source, the ortho - and para- substituted analogs (5) (R=o,p-C=CH) as well as their

Carrier-free cellular uptake and the gene-silencing activity of the lipophilic siRNAs is strongly affected by the length of the linker between siRNA and lipophilic group.

PubMed

Petrova, Natalya S; Chernikov, Ivan V; Meschaninova, Mariya I; Dovydenko, Iiya S; Venyaminova, Aliya G; Zenkova, Marina A; Vlassov, Valentin V; Chernolovskaya, Elena L

2012-03-01

The conjugation of siRNA to molecules, which can be internalized into the cell via natural transport mechanisms, can result in the enhancement of siRNA cellular uptake. Herein, the carrier-free cellular uptake of nuclease-resistant anti-MDR1 siRNA equipped with lipophilic residues (cholesterol, lithocholic acid, oleyl alcohol and litocholic acid oleylamide) attached to the 5'-end of the sense strand via oligomethylene linker of various length was investigated. A convenient combination of H-phosphonate and phosphoramidite methods was developed for the synthesis of 5'-lipophilic conjugates of siRNAs. It was found that lipophilic siRNA are able to effectively penetrate into HEK293, HepG2 and KB-8-5 cancer cells when used in a micromolar concentration range. The efficiency of the uptake is dependent upon the type of lipophilic moiety, the length of the linker between the moiety and the siRNA and cell type. Among all the conjugates tested, the cholesterol-conjugated siRNAs with linkers containing from 6 to 10 carbon atoms demonstrate the optimal uptake and gene silencing properties: the shortening of the linker reduces the efficiency of the cellular uptake of siRNA conjugates, whereas the lengthening of the linker facilitates the uptake but retards the gene silencing effect and decreases the efficiency of the silencing.

Synthesis of novel 4-functionalized 1,5-diaryl-1,2,3-triazoles containing benzenesulfonamide moiety as carbonic anhydrase I, II, IV and IX inhibitors.

PubMed

Vats, Lalit; Sharma, Vikas; Angeli, Andrea; Kumar, Rajiv; Supuran, Claudiu T; Sharma, Pawan K

2018-04-25

The design, synthesis and biological evaluation of a library of 1,2,3-triazole carboxylates incorporating carboxylic acid, hydroxymethyl, carboxylic acid hydrazide, carboxamide and benzenesulfonamide moieties is disclosed. All the novel compounds were investigated for their inhibition potential against carbonic anhydrase (CA, EC 4.2.1.1) human (h) isoforms hCA I, II, IV and IX, well established drug targets. The cytosolic isoform hCA I was inhibited with K i 's ranging between 53.2 nM and 7.616 μM whereas the glaucoma associated cytosolic isoform hCA II was inhibited with K i 's in the range 21.8 nM-0.807 μM. The membrane bound isoform hCA IV, involved in glaucoma and retinitis pigmentosa among others, was effectively inhibited by some of these compounds with K i  < 60 nM, better than the reference drug acetazolamide (AAZ). The tumor associated isoform hCA IX, a recently validated antitumor/antimetastatic drug target, was also effectively inhibited by some of the new sulfonamides, which possess thus the potential to be used as tools for exploring in more details the selective inhibition of hCAs involved in various pathologies. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

[Chemotherapeutic characterization of new nitrosourea compounds].

PubMed

Zeller, W J; Berger, M R; Eisenbrand, G; Petru, E

1988-01-01

The development of new nitrosoureas is described using selected examples. Results obtained with water-soluble analogs and with compounds linked to biomolecules as for instance amino acids, oligopeptides and steroids, are presented. The pronounced antineoplastic effect of some water-soluble analogs is paralleled by an increased rate of DNA-interstrand cross-links and by an increased suppression of hematopoietic stem cells. The suppression of bone marrow stem cells is followed by their rapid regeneration. Water-soluble nitrosoureas induce significant less inhibition of glutathione reductase as compared with established compounds. With regard to long-term toxicity and carcinogenicity water-soluble are superior to established compounds as for instance BCNU. Linking of the nitrosourea moiety to amino acids and oligopeptides led to some analogs with outstanding therapeutic ratio. Out of a group of steroid-linked nitrosoureas, CNC-L-alanine-estradiol-17-ester (CNC-ala-17-E2) is chosen to demonstrate the possibility of reducing bone marrow toxicity despite unchanged or increased therapeutic activity by attachment of the nitrosourea moiety to a steroid. Results of a comparative interspecies in vitro evaluation of CNC-ala-17-E2 in transplanted MXT mammary carcinoma of the mouse, MNU-induced autochthonous rat mammary carcinoma and primary human mammary carcinomas are presented and the question is discussed to what extent in vitro activity of such receptor agents using the tumor stem cell assay reflects their in vivo activity.

Zeolite-catalyzed hydrogenation of carbon dioxide and ethene.

PubMed

Chan, Bun; Radom, Leo

2008-07-30

Ab initio molecular orbital theory and density functional theory calculations have been used to study the three-stage zeolite-catalyzed hydrogenation of CO2 to methanol and the hydrogenation of C2H 4 to ethane, with the aim of designing an effective zeolite catalyst for these reactions. Both Brønsted acid (XH) and alkali metal (XM) sites in model zeolites (-X-Al-XH- or -X-Al-XM-) have been examined. It is found that appropriately designed zeolites can provide excellent catalysis for these reactions, particularly for the hydrogenation of CO2, HCO2H and CH2O, with uncatalyzed barriers of more than 300 kJ mol(-1) being reduced to as little as 17 kJ mol(-1) (in the case of CH2O). The reaction barrier depends on the acidity of the XH moiety or the nature of the metal cation M in the XM moiety, and the basicity of the adjacent X group in the catalyst. For a catalyst based on alkali metal zeolites (XM), the catalytic activity is relatively insensitive to the nature of X in the XM group. As a result, the catalytic activity for these types of zeolites increases as X becomes more basic. We propose that alkali metal zeolites with Ge and N incorporated into the framework could be very effective catalysts for hydrogenation processes.

Solvent-free, microwave-assisted synthesis of thiophene oligomers via Suzuki coupling.

PubMed

Melucci, Manuela; Barbarella, Giovanna; Sotgiu, Giovanna

2002-12-13

The purpose of this study was to obtain a rapid, efficient, and environmentally friendly methodology for the synthesis of highly pure thiophene oligomers. The solvent-free, microwave-assisted coupling of thienyl boronic acids and esters with thienyl bromides, using aluminum oxide as the solid support, allowed us to rapidly check the reaction trends on changing times, temperature, catalyst, and base and easily optimize the experimental conditions to obtain the targeted product in fair amounts. This procedure offers a novel, general, and very rapid route to the preparation of soluble thiophene oligomers. Thus, for example, quaterthiophene was obtained in 6 min by reaction of 2-bromo-2,2'-bithiophene with bis(pinacolato)diboron (isolated yield 65%), whereas quinquethiophene was obtained in 11 min by reaction of dibromoterthiophene with thienylboronic acid (isolated yield 74%). The synthesis of new chiral 2,2'-bithiophenes is reported. The detailed analysis of the byproducts of some reactions allowed us to elucidate a few aspects of reaction mechanisms. While the use of microwaves proved to be very convenient for the coupling between conventional thienyl moieties, the same was not true for the coupling of thienyl rings to thienyl-S,S-dioxide moieties. Indeed, in this case, the targeted product was obtained in low yields because of the competitive, accelerated, Diels-Alder reaction that affords a variety of condensation products.

Efficient modulation of γ-aminobutyric acid type A receptors by piperine derivatives.

PubMed

Schöffmann, Angela; Wimmer, Laurin; Goldmann, Daria; Khom, Sophia; Hintersteiner, Juliane; Baburin, Igor; Schwarz, Thomas; Hintersteininger, Michael; Pakfeifer, Peter; Oufir, Mouhssin; Hamburger, Matthias; Erker, Thomas; Ecker, Gerhard F; Mihovilovic, Marko D; Hering, Steffen

2014-07-10

Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates γ-aminobutyric acid type A receptors (GABAAR). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced chloride current modulation (IGABA-max = 1673% ± 146%, EC50 = 51.7 ± 9.5 μM), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 ± 1.8 μM, IGABA-max = 760% ± 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABAAR modulators.

Efficient Modulation of γ-Aminobutyric Acid Type A Receptors by Piperine Derivatives

PubMed Central

2014-01-01

Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates γ-aminobutyric acid type A receptors (GABAAR). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were expressed in Xenopus laevis oocytes. Structure–activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced chloride current modulation (IGABA-max = 1673% ± 146%, EC50 = 51.7 ± 9.5 μM), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 ± 1.8 μM, IGABA-max = 760% ± 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABAAR modulators. PMID:24905252

Chemical and physical analyses of wax ester properties

PubMed Central

Patel, Sejal; Nelson, Dennis R.; Gibbs, Allen G.

2001-01-01

Wax esters are major constituents of the surface lipids in many terrestrial arthropods, but their study is complicated by their diversity. We developed a procedure for quantifying isomers in mixtures of straight-chain saturated and unsaturated wax esters having the same molecular weights, using single-ion monitoring of the total ion current data from gas chromatography-mass spectrometry. We examined the biological consequences of structural differences by measuring the melting temperatures, Tm, of >60 synthetic wax esters, containing 26–48 carbon atoms. Compounds containing saturated alcohol and acid moieties melted at 38–73°C. The main factor affecting Tm was the total chain length of the wax ester, but the placement of the ester bond also affected Tm. Insertion of a double bond into either the alcohol or acid moiety decreased Tm by ∼30°C. Simple mixtures of wax esters with n-alkanes melted several °C lower than predicted from the melting points of the component lipids. Our results indicate that the wax esters of primary alcohols that are most typically found on the cuticle of terrestrial arthropods occur in a solid state under physiological conditions, thereby conferring greater waterproofing. Wax esters of secondary alcohols, which occur on melanopline grasshoppers, melted >60°C below primary esters of the same molecular weight and reduced Tm of the total surface lipids to environmental values. PMID:15455064

Assembly of D-alanyl-lipoteichoic acid in Lactobacillus casei: mutants deficient in the D-alanyl ester content of this amphiphile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ntamere, A.S.; Taron, D.J.; Neuhaus, F.C.

D-Alanyl-lipoteichoic acid (D-alanyl-LTA) from Lactobacillus casei ATCC 7469 contains a poly(glycerophosphate) moiety that is acylated with D-alanyl ester residues. The physiological function of these residues is not well understood. Five mutant strains of this organism that are deficient in the esters of this amphiphile were isolated and characterized. When compared with the parent, strains AN-1 and AN-4 incorporated less than 10% of D-(/sup 14/C)alanine into LTA, whereas AN-2, AN-3, and AN-5 incorporated 50%. The synthesis of D-(/sup 14/C)alanyl-lipophilic LTA was virtually absent in the first group and was approximately 30% in the second group. The mutant strains synthesized and selectedmore » the glycolipid anchor for LTA assembly. In addition, all of the strains synthesized the poly(glycerophosphate) moiety of LTA to the same extent as did the parent or to a greater extent. It was concluded that the membranes from the mutant strains AN-1 and AN-4 are defective for D-alanylation of LTA even though acceptor LTA is present. Mutant strains AN-2 and AN-3 appear to be partially deficient in the amount of the D-alanine-activating enzyme. Aberrant morphology and defective cell separation appear to result from this deficiency in D-alanyl ester content.« less

Benzoic Acid Derivatives with Trypanocidal Activity: Enzymatic Analysis and Molecular Docking Studies toward Trans-Sialidase.

PubMed

Kashif, Muhammad; Moreno-Herrera, Antonio; Villalobos-Rocha, Juan Carlos; Nogueda-Torres, Benjamín; Pérez-Villanueva, Jaime; Rodríguez-Villar, Karen; Medina-Franco, José Lius; de Andrade, Peterson; Carvalho, Ivone; Rivera, Gildardo

2017-10-30

Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans -sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans -sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds ( 14 , 18 , and 19 ) sharing a para -aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC 50 ) was <0.15 µM on the NINOA strain, and LC 50 < 0.22 µM on the INC-5 strain. Additionally, compound 18 showed a moderate inhibition (47%) on the trans -sialidase enzyme and a binding model similar to DANA (pattern A).

Structural characterization of aquatic humic material. 2. Phenolic content and its relationship to chlorination mechanism in an isolated aquatic fulvi acid

USGS Publications Warehouse

Norwood, D.L.; Christman, R.F.; Hatcher, P.G.

1987-01-01

The complementary techniques of solid-state 13G nuclear magnetic resonance spectroscopy and chemical degradation were utilized to examine the lignin/phenolic substructure of an isolated aquatic fulvic acid capable of producing upon aqueous chlorination a number of organohalides typically found in municipal drinking water. Results indicate that while phenolic moieties are present in the fulvic acid, they account for only a minor fraction of the total carbon. A sequential chemical degradation experiment utilizing aqueous chlorine and CuO demonstrated that the lignin/phenolic substructure was attacked by the chlorine. It is concluded that while phenolic ring rupture mechanisms appear to be important in organohalide generation, other aqueous chlorination mechanisms involving aliphatic and other types of aromatic structures should also be considered. ?? 1987 American Chemical Society.

Structure of the Cell Wall of Bacillus stearothermophilus: Mode of Action of a Thermophilic Bacteriophage Lytic Enzyme

PubMed Central

Welker, N. E.

1971-01-01

The mode of action of a bacteriophage lytic enzyme on cell walls of Bacillus stearothermophilus (NCA 1503-4R) has been investigated. The enzyme is an endopeptidase which catalyzes the hydrolysis of the l-alanyl-d-glutamyl linkage in peptide subunits of the cell wall peptidoglycan. Preliminary studies on the soluble components in lytic cell wall digests indicate that the glycan moiety is composed of alternating glucosamine and muramic acid; one half of the muramic acid residues contain the tripeptide, l-alanyl-d-glutamyldiaminopimelic acid, and the remaining residues contain the tetrapeptide, l-alanyl-d-glutamyldiaminopimeyl-d-alanine. Almost one half of the peptide subunits are involved in cross-linkages of chemotype I. A structure for the cell wall peptidoglycan is proposed in the light of these findings. PMID:4255338

Grafting of 4-aminomethylbenzensulfonamide-lipoic acid conjugate on gold nanoparticles

NASA Astrophysics Data System (ADS)

Stiti, M.; Bouzit, H.; Abdaoui, M.; Winum, J. Y.

2012-02-01

In this paper, we describe the synthesis of goldnanoparticles bearing aminomethylbenzensulfonamide via a lipoyl moiety. The resulting stable nanoparticles with an average size of 4.0 nm have been achieved by a facile and high-yielding one phase method, by the action of 4-aminomethylbenzensulfonamide-lipoic acid bioconjugate on chloroauric acide, using dimethylsulfoxide (DMSO) as the solvent and sodium tetrahydridoborate (NaBH4) as the reducing agent. UV-vis absorption, transmission electron microscopy (TEM) and X-ray diffraction were used to analyse the morphology and the structure of the obtained nanoparticles. Preliminary study shows that these new nanoparticles are endowed with highly and specific inhibitory activity for the isoform (IX) of carbonic anhydrase over expressed in many cancers, and are therefore attractive candidate to be used both in diagnosis and in treatment of tumours.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grossman, L.

Two uracil photoproducts are formed when polyuridylic acid (poly U) is irradiated with ultraviolet light. A molecule of water may add at the 4,-5 double bond of the uracil moieties as a result of irradiation and these may be reconverted to uracil by base-catalyzed dehydration. The other photoproduct formed is a uracil-uracil dimer, which reverts to uracil by reirradiation at lower wavelengths of ultraviolet light. The effects of irradiated poly U were studied iu the amino acid incorporating system in which dehydration and photoreversal of the irradiated poly U separated some of the ultraviolet effects. It was concluded that themore » water adduct is responsible for the coding transition of C 14-phenylalanine to C 14-serine, and the formation of dimer results in the loss of the incorporation of C 14-phenylalanine, which is not replaced by any other amino acid.« less

Surface modification of calcium-copper hydroxyapatites using polyaspartic acid

NASA Astrophysics Data System (ADS)

Othmani, Masseoud; Aissa, Abdallah; Bachoua, Hassen; Debbabi, Mongi

2013-01-01

Mixed calcium-copper hydroxyapatite (Ca-CuHAp), with general formula Ca(10-x)Cux(PO4)6(OH)2, where 0 ≤ x ≤ 0.75 was prepared in aqueous medium in the presence of different concentrations of poly-L-aspartic acid (PASP). XRD, IR, TG-DTA, TEM-EDX, AFM and chemical analyses were used to characterize the structure, morphology and composition of the products. All techniques show the formation of new hybrid compounds Ca-CuHAp-PASP. The presence of the grafting moiety on the apatitic material is more significant with increasing of copper amount and/or organic concentration in the starting solution. These increases lead to the affectation of apatite crystallinity. The IR spectroscopy shows the conservation of (Psbnd OH) band of (HPO4)2- groups, suggesting that PASP acid was interacted only with metallic cations of hydroxyapatite.

Quantum Mechanics/Molecular Mechanics Study of the Sialyltransferase Reaction Mechanism.

PubMed

Hamada, Yojiro; Kanematsu, Yusuke; Tachikawa, Masanori

2016-10-11

The sialyltransferase is an enzyme that transfers the sialic acid moiety from cytidine 5'-monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to the terminal position of glycans. To elucidate the catalytic mechanism of sialyltransferase, we explored the potential energy surface along the sialic acid transfer reaction coordinates by the hybrid quantum mechanics/molecular mechanics method on the basis of the crystal structure of sialyltransferase CstII. Our calculation demonstrated that CstII employed an S N 1-like reaction mechanism via the formation of a short-lived oxocarbenium ion intermediate. The computational barrier height was 19.5 kcal/mol, which reasonably corresponded with the experimental reaction rate. We also found that two tyrosine residues (Tyr156 and Tyr162) played a vital role in stabilizing the intermediate and the transition states by quantum mechanical interaction with CMP.

Sensing Reversible Protein–Ligand Interactions with Single-Walled Carbon Nanotube Field-Effect Transistors

PubMed Central

2015-01-01

We report on the reversible detection of CaptAvidin, a tyrosine modified avidin, with single-walled carbon nanotube (SWNT) field-effect transistors (FETs) noncovalently functionalized with biotin moieties using 1-pyrenebutyric acid as a linker. Binding affinities at different pH values were quantified, and the sensor’s response at various ionic strengths was analyzed. Furthermore, protein “fingerprints” of NeutrAvidin and streptavidin were obtained by monitoring their adsorption at several pH values. Moreover, gold nanoparticle decorated SWNT FETs were functionalized with biotin using 1-pyrenebutyric acid as a linker for the CNT surface and (±)-α-lipoic acid linkers for the gold surface, and reversible CaptAvidin binding is shown, paving the way for potential dual mode measurements with the addition of surface enhanced Raman spectroscopy (SERS). PMID:25126155

Rapid embryonic accretion of docosahexaenoic acid (DHA) in the brain of an altricial bird with an aquatic-based maternal diet.

PubMed

Price, Edwin R; Sirsat, Sarah K G; Sirsat, Tushar S; Venables, Barney J; Dzialowski, Edward M

2018-05-31

Docosahexaenoic acid (DHA) is an important and abundant fatty acid moiety in vertebrate brains. We measured brain phospholipid composition during development in red-winged blackbirds ( Agelaius phoeniceus ), an altricial species that breeds in aquatic habitats. We also manipulated diet by feeding nestlings fish oil or sunflower oil. Finally, we assessed selective uptake of yolk by comparing the yolk fatty acid composition of freshly laid eggs and day-old hatchlings. Relative to other altricial species, blackbirds achieved high DHA in brain phospholipids (20% of phospholipid fatty acids in day-old hatchlings). This was not a result of selective uptake from the yolk, but rather a consequence of a high proportion of DHA in the yolk (2.5% of total lipids) at laying. Our dietary study confirmed that nestling brains are sensitive to fatty acid supply. Red-winged blackbirds may be able to advance cognitive development relative to other altricial species due to their aquatic maternal diet. © 2018. Published by The Company of Biologists Ltd.

Hyodeoxycholic acid derivatives as liver X receptor α and G-protein-coupled bile acid receptor agonists

NASA Astrophysics Data System (ADS)

de Marino, Simona; Carino, Adriana; Masullo, Dario; Finamore, Claudia; Marchianò, Silvia; Cipriani, Sabrina; di Leva, Francesco Saverio; Catalanotti, Bruno; Novellino, Ettore; Limongelli, Vittorio; Fiorucci, Stefano; Zampella, Angela

2017-02-01

Bile acids are extensively investigated for their potential in the treatment of human disorders. The liver X receptors (LXRs), activated by oxysterols and by a secondary bile acid named hyodeoxycholic acid (HDCA), have been found essential in the regulation of lipid homeostasis in mammals. Unfortunately, LXRα activates lipogenic enzymes causing accumulation of lipid in the liver. In addition to LXRs, HDCA has been also shown to function as ligand for GPBAR1, a G protein coupled receptor for secondary bile acids whose activation represents a promising approach to liver steatosis. In the present study, we report a library of HDCA derivatives endowed with modulatory activity on the two receptors. The lead optimization of HDCA moiety was rationally driven by the structural information on the binding site of the two targets and results from pharmacological characterization allowed the identification of hyodeoxycholane derivatives with selective agonistic activity toward LXRα and GPBAR1 and notably to the identification of the first example of potent dual LXRα/GPBAR1 agonists. The new chemical entities might hold utility in the treatment of dyslipidemic disorders.

Nicotinic Acid Adenine Dinucleotide Phosphate Analogs Substituted on the Nicotinic Acid and Adenine Ribosides. Effects on Receptor-Mediated Ca2+ release

PubMed Central

Trabbic, Christopher J.; Zhang, Fan; Walseth, Timothy F.; Slama, James T.

2015-01-01

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a Ca2+ releasing intracellular second messenger in both mammals and echinoderms. We report that large functionalized substituents introduced at the nicotinic acid 5-position are recognized by the sea urchin receptor, albeit with a 20–500 fold loss in agonist potency. 5-(3-Azidopropyl)-NAADP was shown to release Ca2+ with an EC50 of 31 µM and to compete with NAADP for receptor binding with an IC50 of 56 nM. Attachment of charged groups to the nicotinic acid of NAADP is associated with loss of activity, suggesting that the nicotinate riboside moiety is recognized as a neutral zwitterion. Substituents (Br- and N3-) can be introduced at the 8-adenosyl position of NAADP while preserving high potency and agonist efficacy and an NAADP derivative substituted at both the 5-position of the nicotinic acid and at the 8-adenosyl position was also recognized although the agonist potency was significantly reduced. PMID:25826221

1-(2-aminophenyl)-1H-1,2,3-triazole-4-carboxylic acid: activity against Gram-positive and Gram-negative pathogens including Vibrio cholerae

NASA Astrophysics Data System (ADS)

Maji, Krishnendu; Haldar, Debasish

2017-10-01

We report a new synthetic aromatic ε-amino acid containing a triazole moiety with antimicrobial potential against Gram-positive, Gram-negative and pathogenic bacteria including Vibrio cholerae. Structure-property relationship studies revealed that all the functional groups are essential to enhance the antimicrobial activity. The 1-(2-aminophenyl)-1H-1,2,3-triazole-4-carboxylic acid was synthesized by click chemistry. From X-ray crystallography, the amino acid adopts a kink-like structure where the phenyl and triazole rings are perpendicular to each other and the amine and acid groups maintain an angle of 60°. The agar diffusion test shows that the amino acid has significant antibacterial activity. The liquid culture test exhibits that the minimum inhibitory concentration (MIC) value for Bacillus subtilis and Vibrio cholerae is 59.5 µg ml-1. FE-SEM experiments were performed to study the morphological changes of bacterial shape after treatment with compound 1. The antimicrobial activity of the amino acid was further studied by DNA binding and degradation study, protein binding, dye-binding assay and morphological analysis. Moreover, the amino acid does not have any harmful effect on eukaryotes.

Production of 3-Oxo-2-(2'-pentenyl)-cyclopentane-1-octanoic Acid in the Fungus Aspergillus oryzae: A Step Towards Heterologous Production of Pyrethrins in Fungi.

PubMed

Mohamed, Maged E; Pahirulzaman, Khomaizon A K; Lazarus, Colin M

2016-03-01

Pyrethrins are natural insecticides, which accumulate to high concentrations in pyrethrum (Chrysanthemum cinerariaefolium) flowers. Synthetic pyrethroids are more stable, more efficacious and cheaper, but contemporary requirements for safe and environmentally friendly pesticides encourage a return to the use of natural pyrethrins, and this would be favoured by development of an efficient route to their production by microbial fermentation. The biosynthesis of pyrethrins involves ester linkage between an acid moiety (chrysanthemoyl or pyrethroyl, synthesised via the mevalonic acid pathway from glucose), and an alcohol (pyrethrolone). Pyrethrolone is generated from 3-oxo-2-(2'-pentenyl)-cyclopentane-1-octanoic acid, which originates from α-linolenic acid via the jasmonic acid biosynthetic cascade. The first four genes in this cascade, encoding lipoxygenase 2, allene-oxide synthase, allene-oxide cyclase 2 and 12-oxophytodienoic acid reductase 3, were amplified from an Arabidopsis thaliana cDNA library, cloned in a purpose-built fungal multigene expression vector and expressed in Aspergillus oryzae. HPLC-MS analysis of the transgenic fungus homogenate gave good evidence for the presence of 3-oxo-2-(2'-pentenyl)-cyclopentane-1-octanoic acid.

Investigation of the acid-base and electromigration properties of 5-azacytosine derivatives using capillary electrophoresis and density functional theory calculations.

PubMed

Geffertová, Denisa; Ali, Syed Tahir; Šolínová, Veronika; Krečmerová, Marcela; Holý, Antonín; Havlas, Zdeněk; Kašička, Václav

2017-01-06

Capillary electrophoresis (CE) and quantum mechanical density functional theory (DFT) were applied to the investigation of the acid-base and electromigration properties of important compounds: newly synthesized derivatives of 5-azacytosine - analogs of efficient antiviral drug cidofovir. These compounds exhibit a strong antiviral activity and they are considered as potential new antiviral agents. For their characterization and application, it is necessary to know their acid-base properties, particularly the acidity constants (pK a ) of their ionogenic groups (the basic N 3 atom of the triazine ring and the acidic phosphonic acid group in the alkyl chain). First, the mixed acidity constants (pK a mix ) of these ionogenic groups and the ionic mobilities of these compounds were determined by nonlinear regression analysis of the pH dependence of their effective electrophoretic mobilities. Effective mobilities were measured by CE in a series of background electrolytes in a wide pH range (2.0-10.5), at constant ionic strength (25mM) and constant temperature (25°C). Subsequently, the pK a mix values were recalculated to thermodynamic pK a values using the Debye-Hückel theory. The thermodynamic pK a value of the NH + moiety at the N 3 atom of the triazine ring was found to be in the range 2.82-3.30, whereas the pK a of the hydrogenphosphonate group reached values from 7.19 to 7.47, depending on the structure of the analyzed compounds. These experimentally determined pK a values were in good agreement with those calculated by quantum mechanical DFT. In addition, DFT calculations revealed that from the four nitrogen atoms in the 5-azacytosine moiety, the N 3 atom of the triazine ring is preferentially protonated. Effective charges of analyzed compounds ranged from zero or close-to-zero values at pH 2 to -2 elementary charges at pH≥9. Ionic mobilities were in the range (-16.7 to -19.1)×10 -9 m 2 V -1 s -1 for univalent anions and in the interval (-26.9 to -30.3)×10 -9 m 2 V -1 s -1 for divalent anions. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural and optical studies on selected web spinning spider silks

NASA Astrophysics Data System (ADS)

Karthikeyani, R.; Divya, A.; Mathavan, T.; Asath, R. Mohamed; Benial, A. Milton Franklin; Muthuchelian, K.

2017-01-01

This study investigates the structural and optical properties in the cribellate silk of the sheet web spider Stegodyphus sarasinorum Karsch (Eresidae) and the combined dragline, viscid silk of the orb-web spiders Argiope pulchella Thorell (Araneidae) and Nephila pilipes Fabricius (Nephilidae). X-ray diffraction (XRD), Fourier transform infra-red (FTIR), Ultraviolet-visible (UV-Vis) and fluorescence spectroscopic techniques were used to study these three spider silk species. X-ray diffraction data are consistent with the amorphous polymer network which is arising from the interaction of larger side chain amino acid contributions due to the poly-glycine rich sequences known to be present in the proteins of cribellate silk. The same amorphous polymer networks have been determined from the combined dragline and viscid silk of orb-web spiders. From FTIR spectra the results demonstrate that, cribellate silk of Stegodyphus sarasinorum, combined dragline viscid silk of Argiope pulchella and Nephila pilipes spider silks are showing protein peaks in the amide I, II and III regions. Further they proved that the functional groups present in the protein moieties are attributed to α-helical and side chain amino acid contributions. The optical properties of the obtained spider silks such as extinction coefficients, refractive index, real and imaginary dielectric constants and optical conductance were studied extensively from UV-Vis analysis. The important fluorescent amino acid tyrosine is present in the protein folding was investigated by using fluorescence spectroscopy. This research would explore the protein moieties present in the spider silks which were found to be associated with α-helix and side chain amino acid contributions than with β-sheet secondary structure and also the optical relationship between the three different spider silks are investigated. Successful spectroscopic knowledge of the internal protein structure and optical properties of the spider silks could permit industrial production of silk-based fibres with unique properties under benign conditions.

Characterization of αX I-Domain Binding to Receptors for Advanced Glycation End Products (RAGE).

PubMed

Buyannemekh, Dolgorsuren; Nham, Sang-Uk

2017-05-31

The β2 integrins are cell surface transmembrane proteins regulating leukocyte functions, such as adhesion and migration. Two members of β2 integrin, αMβ2 and αXβ2, share the leukocyte distribution profile and integrin αXβ2 is involved in antigen presentation in dendritic cells and transendothelial migration of monocytes and macrophages to atherosclerotic lesions. Receptor for advanced glycation end products (RAGE), a member of cell adhesion molecules, plays an important role in chronic inflammation and atherosclerosis. Although RAGE and αXβ2 play an important role in inflammatory response and the pathogenesis of atherosclerosis, the nature of their interaction and structure involved in the binding remain poorly defined. In this study, using I-domain as a ligand binding motif of αXβ2, we characterize the binding nature and the interacting moieties of αX I-domain and RAGE. Their binding requires divalent cations (Mg 2+ and Mn 2+ ) and shows an affinity on the sub-micro molar level: the dissociation constant of αX I-domains binding to RAGE being 0.49 μM. Furthermore, the αX I-domains recognize the V-domain, but not the C1 and C2-domains of RAGE. The acidic amino acid substitutions on the ligand binding site of αX I-domain significantly reduce the I-domain binding activity to soluble RAGE and the alanine substitutions of basic amino acids on the flat surface of the V-domain prevent the V-domain binding to αX I-domain. In conclusion, the main mechanism of αX I-domain binding to RAGE is a charge interaction, in which the acidic moieties of αX I-domains, including E244, and D249, recognize the basic residues on the RAGE V-domain encompassing K39, K43, K44, R104, and K107.

Hydroquinone-Mediated Redox Cycling of Iron and Concomitant Oxidation of Hydroquinone in Oxic Waters under Acidic Conditions: Comparison with Iron-Natural Organic Matter Interactions.

PubMed

Jiang, Chao; Garg, Shikha; Waite, T David

2015-12-15

Interactions of 1,4-hydroquinone with soluble iron species over a pH range of 3-5 in the air-saturated and partially deoxygenated solution are examined here. Our results show that 1,4-hydroquinone reduces Fe(III) in acidic conditions, generating semiquinone radicals (Q(•-)) that can oxidize Fe(II) back to Fe(III). The oxidation rate of Fe(II) by Q(•-)increases with increase in pH due to the speciation change of Q(•-) with its deprotonated form (Q(•-)) oxidizing Fe(II) more rapidly than the protonated form (HQ(•)). Although the oxygenation of Fe(II) is negligible at pH < 5, O2 still plays an important role in iron redox transformation by rapidly oxidizing Q(•-) to form benzoquinone (Q). A kinetic model is developed to describe the transformation of quinone and iron under all experimental conditions. The results obtained here are compared with those obtained in our previous studies of iron-Suwannee River fulvic acid (SRFA) interactions in acidic solutions and support the hypothesis that hydroquinone moieties can reduce Fe(III) in natural waters. However, the semiquinone radicals generated in pure hydroquinone solution are rapidly oxidized by dioxygen, while the semiquinone radicals generated in SRFA solution are resistant to oxidation by dioxygen, with the result that steady-state semiquinone concentrations in SRFA solutions are 2-3 orders of magnitude greater than in solutions of 1,4-hydroquinone. As a result, semiquinone moieties in SRFA play a much more important role in iron redox transformations than is the case in solutions of simple quinones such as 1,4-hydroquinone. This difference in the steady-state concentration of semiquinone species has a dramatic effect on the cycling of iron between the +II and +III oxidation states, with iron turnover frequencies in solutions containing SRFA being 10-20 times higher than those observed in solutions of 1,4-hydroquinone.

Distinct moieties underlie biphasic H+ gating of connexin43 channels, producing a pH optimum for intercellular communication

PubMed Central

Garciarena, Carolina D.; Malik, Akif; Swietach, Pawel; Moreno, Alonso P.; Vaughan-Jones, Richard D.

2018-01-01

Most mammalian cells can intercommunicate via connexin-assembled, gap-junctional channels. To regulate signal transmission, connexin (Cx) channel permeability must respond dynamically to physiological and pathophysiological stimuli. One key stimulus is intracellular pH (pHi), which is modulated by a tissue’s metabolic and perfusion status. Our understanding of the molecular mechanism of H+ gating of Cx43 channels—the major isoform in the heart and brain—is incomplete. To interrogate the effects of acidic and alkaline pHi on Cx43 channels, we combined voltage-clamp electrophysiology with pHi imaging and photolytic H+ uncaging, performed over a range of pHi values. We demonstrate that Cx43 channels expressed in HeLa or N2a cell pairs are gated biphasically by pHi via a process that consists of activation by H+ ions at alkaline pHi and inhibition at more acidic pHi. For Cx43 channel–mediated solute/ion transmission, the ensemble of these effects produces a pHi optimum, near resting pHi. By using Cx43 mutants, we demonstrate that alkaline gating involves cysteine residues of the C terminus and is independent of motifs previously implicated in acidic gating. Thus, we present a molecular mechanism by which cytoplasmic acid–base chemistry fine tunes intercellular communication and establishes conditions for the optimal transmission of solutes and signals in tissues, such as the heart and brain.—Garciarena, C. D., Malik, A., Swietach, P., Moreno, A. P., Vaughan-Jones, R. D. Distinct moieties underlie biphasic H+ gating of connexin43 channels, producing a pH optimum for intercellular communication. PMID:29183963

Benzene-1,3-dicarboxylic acid 2,5-dimethylpyrrole derivatives as multiple inhibitors of bacterial Mur ligases (MurC-MurF).

PubMed

Perdih, Andrej; Hrast, Martina; Barreteau, Hélène; Gobec, Stanislav; Wolber, Gerhard; Solmajer, Tom

2014-08-01

Enzymes catalyzing the biosynthesis of bacterial peptidoglycan represent traditionally a collection of highly selective targets for novel antibacterial drug design. Four members of the bacterial Mur ligase family-MurC, MurD, MurE and MurF-are involved in the intracellular steps of peptidoglycan biosynthesis, catalyzing the synthesis of the peptide moiety of the Park's nucleotide. In our previous virtual screening campaign, a chemical class of benzene-1,3-dicarboxylic acid 2,5-dimethylpyrrole derivatives exhibiting dual MurD/MurE inhibition properties was discovered. In the present study we further investigated this class of compounds by performing inhibition assays on all four Mur ligases (MurC-MurF). Furthermore, molecular dynamics (MD) simulation studies of one of the initially discovered compound 1 were performed to explore its geometry as well as its energetic behavior based on the Linear Interaction Energy (LIE) method. Further in silico virtual screening (VS) experiments based on the parent active compound 1 were conducted to optimize the discovered series. Selected hits were assayed against all Escherichia coli MurC-MurF enzymes in biochemical inhibition assays and molecules 10-14 containing benzene-1,3-dicarboxylic acid 2,5-dimethylpyrrole coupled with five member-ring rhodanine moiety were found to be multiple inhibitors of the whole MurC-MurF cascade of bacterial enzymes in the micromolar range. Steady-state kinetics studies suggested this class to act as competitive inhibitors of the MurD enzyme towards d-Glu. These compounds represent novel valuable starting point in the development of novel antibacterial agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of the Binding Moiety Mediating the Interaction between Monocarboxylate Transporters and Carbonic Anhydrase II*

PubMed Central

Noor, Sina Ibne; Dietz, Steffen; Heidtmann, Hella; Boone, Christopher D.; McKenna, Robert; Deitmer, Joachim W.; Becker, Holger M.

2015-01-01

Proton-coupled monocarboxylate transporters (MCTs) mediate the exchange of high energy metabolites like lactate between different cells and tissues. We have reported previously that carbonic anhydrase II augments transport activity of MCT1 and MCT4 by a noncatalytic mechanism, while leaving transport activity of MCT2 unaltered. In the present study, we combined electrophysiological measurements in Xenopus oocytes and pulldown experiments to analyze the direct interaction between carbonic anhydrase II (CAII) and MCT1, MCT2, and MCT4, respectively. Transport activity of MCT2-WT, which lacks a putative CAII-binding site, is not augmented by CAII. However, introduction of a CAII-binding site into the C terminus of MCT2 resulted in CAII-mediated facilitation of MCT2 transport activity. Interestingly, introduction of three glutamic acid residues alone was not sufficient to establish a direct interaction between MCT2 and CAII, but the cluster had to be arranged in a fashion that allowed access to the binding moiety in CAII. We further demonstrate that functional interaction between MCT4 and CAII requires direct binding of the enzyme to the acidic cluster 431EEE in the C terminus of MCT4 in a similar fashion as previously shown for binding of CAII to the cluster 489EEE in the C terminus of MCT1. In CAII, binding to MCT1 and MCT4 is mediated by a histidine residue at position 64. Taken together, our results suggest that facilitation of MCT transport activity by CAII requires direct binding between histidine 64 in CAII and a cluster of glutamic acid residues in the C terminus of the transporter that has to be positioned in surroundings that allow access to CAII. PMID:25561737

A novel dextran hydrogel linking trans-ferulic acid for the stabilization and transdermal delivery of vitamin E.

PubMed

Cassano, Roberta; Trombino, Sonia; Muzzalupo, Rita; Tavano, Lorena; Picci, Nevio

2009-05-01

Long-term exposure of the skin to UV light causes degenerative effects, which can be minimized by using antioxidant formulations. The major challenge in this regard is that a significant amount of antioxidant should reach at the site for effective photoprotection. However, barrier properties of the skin limit their use. In the present study, vitamin E (alpha-tocopherol) was loaded into a dextran hydrogel containing ferulic moieties, covalently linked, to improve its topical delivery, and also to increase its relative poor stability, which is due to direct exposure to UV light. Methacrylic groups were first introduced onto the dextran polymer backbones, then the obtained methacrylated dextran was copolymerized with aminoethyl methacrylate, and subsequently esterificated with trans-ferulic acid. The new biopolymer was characterized by Fourier transform infrared spectroscopy. The values of content of phenolic groups were determined. Its ability in inhibiting lipid peroxidation in rat liver microsomal membranes induced in vitro by a source of free radicals, that is tert-butyl hydroperoxide, was studied. Hydrogel was also characterized for swelling behaviour, vitamin E loading efficiency, release, and deposition on the rabbit skin. Additionally, vitamin E deposition was compared through hydrogels, respectively, containing and not containing trans-ferulic acid. The results showed that ferulate hydrogel was a more effective carrier in protecting vitamin E from photodegradation than hydrogel without antioxidant moieties. Then antioxidant hydrogel could be of potential use for cosmetic and pharmaceutical purposes as carrier of vitamin E that is an antioxidant that reduces erythema, photoaging, photocarcinogenesis, edema, and skin hypersensitivity associated with exposure to ultraviolet B (UVB) radiation, because of its protective effects.

The position of rumenic acid on triacylglycerols alters its bioavailability in rats.

PubMed

Chardigny, J M; Masson, E; Sergiel, J P; Darbois, M; Loreau, O; Noël, J P; Sébédio, J-L

2003-12-01

The metabolic fate of rumenic acid (9cis,11trans-octadecenoic acid) related to its position on the glycerol moiety has not yet been studied. In the present work, synthetic triacylglycerols (TAG) esterified with oleic and rumenic acids were prepared. Rats were force-fed synthetic dioleyl monorumenyl glycerol with (14)C labeled rumenic acid in the internal (sn-2) or in the external position (sn-1 or sn-3). Rats were then placed in metabolic cages for 16 h. At the end of the experiment, the radioactivity in tissues, carcass and expired CO(2) was measured. Rumenic acid that was esterified at the external positions on the TAG was better absorbed and oxidized to a greater extent than when esterified at the internal position. The fatty acid from the 2-TAG form was also better incorporated into the rat carcass. In the liver, rumenic acid appeared mainly in TAG (50%) and to a lesser extent in phospholipids (33%) whatever its dietary form. Moreover, analyses of lipids from Camembert cheese and butter revealed that rumenic acid was located mainly on the sn-1 or sn-3 positions (74%). Taken together, these data suggest that rumenic acid from dairy fat may be well absorbed and used extensively for energy production.

3'-End labeling of nucleic acids by a polymerase ribozyme.

PubMed

Samanta, Biswajit; Horning, David P; Joyce, Gerald F

2018-06-13

A polymerase ribozyme can be used to label the 3' end of RNA or DNA molecules by incorporating a variety of functionalized nucleotide analogs. Guided by a complementary template, the ribozyme adds a single nucleotide that may contain a fluorophore, biotin, azide or alkyne moiety, thus enabling the detection and/or capture of selectively labeled materials. Employing a variety of commercially available nucleotide analogs, efficient labeling was demonstrated for model RNAs and DNAs, human microRNAs and natural tRNA.

Domino approach to 2-aroyltrimethoxyindoles as novel heterocyclic combretastatin A4 analogues.

PubMed

Arthuis, Martin; Pontikis, Renée; Chabot, Guy G; Quentin, Lionel; Scherman, Daniel; Florent, Jean-Claude

2011-01-01

Two series of 2-aroyltrimethoxyindoles were designed to investigate the effects of the replacement of the trimethoxyphenyl ring of phenstatin with a trimethoxyindole moiety. These compounds were efficiently prepared through a domino palladium-catalyzed sequence from 2-gem-dibromovinylanilines substituted by three methoxy groups and arylboronic acids under carbon monoxide atmosphere. These novel heterocyclic combretastatin A4 analogues were evaluated for their cell growth inhibitory properties and their ability to inhibit the tubulin polymerization. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Structure of the choline-binding domain of Spr1274 in Streptococcus pneumoniae.

PubMed

Zhang, Zhenyi; Li, Wenzhe; Frolet, Cecile; Bao, Rui; di Guilmi, Anne Marie; Vernet, Thierry; Chen, Yuxing

2009-08-01

Spr1274 is a putative choline-binding protein that is bound to the cell wall of Streptococcus pneumoniae through noncovalent interactions with the choline moieties of teichoic and lipoteichoic acids. Its function is still unknown. The crystal structure of the choline-binding domain of Spr1274 (residues 44-129) was solved at 2.38 A resolution with three molecules in the asymmetric unit. It may provide a structural basis for functional analysis of choline-binding proteins.

Simple assembly of polysubstituted pyrazoles and isoxazoles via ring closure-ring opening domino reaction of 3-acyl-4,5-dihydrofurans with hydrazines and hydroxylamine.

PubMed

Chagarovskiy, Alexey O; Budynina, Ekaterina M; Ivanova, Olga A; Rybakov, Victor B; Trushkov, Igor V; Melnikov, Mikhail Ya

2016-03-14

A convenient general approach to 2-(pyrazol-4-yl)- and 2-(isoxazol-4-yl)ethanols based on the Brønsted acid-initiated reaction of 3-acyl-4,5-dihydrofurans with hydrazines or hydroxylamine was developed. Further transformation of the alcohol moiety in 2-(pyrazolyl)ethanols affording 2-(pyrazolyl)ethylamine as potent bioactive compounds as well as pyrazole-substituted derivatives of antitumor alkaloid crispine A was elaborated.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park Y. S.; Kale, T.; Wu, Q.

A series of diketopyrrolopyrrole(DPP)-based small molecules have been synthesized by palladium-catalyzed coupling reactions. Electron-donating moieties (benzothiophene, benzoselenophene, and benzotellurophene) are bridged by an electron-withdrawing DPP unit to generate donor-acceptor-donor (D-A-D) type molecules. We observe red-shifts in absorption spectra of these compounds by varying heteroatoms from sulfur to tellurium. In bulk heterojunction solar cells with [6,6]phenyl-C61-butyric acid methyl ester (PC61BM) as acceptor, we obtain power conversion efficiencies of 2.4% (benzothiophene), 4.1% (benzoselenophene), and 3.0% (benzotellurophene), respectively.

DNA sensing by a Eu-binding peptide containing a proflavine unit.

PubMed

Ancel, Laetitia; Gateau, Christelle; Lebrun, Colette; Delangle, Pascale

2013-01-18

Synthesis of a lanthanide-binding peptide (LBP) for the detection of double-stranded DNA is presented. A proflavine moiety was introduced into a high affinity LBP involving two unnatural chelating amino acids in the Ln ion coordination. The Eu(3+)-LBP complex is demonstrated to bind to ct-DNA and to sensitize Eu luminescence. The DNA binding process is effectively detected via the Eu-centered luminescence thanks to the intimate coupling between the LBP scaffold and DNA intercalating unit.

Action of nucleotide phosphotransferase of Escherichia coli on nicotinamide riboside and nicotinamide mononucleotide.

PubMed Central

Brunngraber, E F; Chargaff, E

1977-01-01

The action of the nucleotide phosphotransferase of Escherichia coli on nicotinamide riboside and on its 5'-phosphate results in the addition of one phosphate moiety to each of the substrates. Although the proof is not conclusive, it is likely that the phosphate group is transferred to the 3'-hydroxyl of the ribose. This is in contrast to the behavior of the enzyme toward NAD in which only the adenylic acid portion is phosphorylated enzymically. PMID:144913

Anilinomethylrhodamines: pH sensitive probes with tunable photophysical properties by substituent effect.

PubMed

Best, Quinn A; Liu, Chuangjun; van Hoveln, Paul D; McCarroll, Matthew E; Scott, Colleen N

2013-10-18

A series of pH dependent rhodamine analogues possessing an anilino-methyl moiety was developed and shown to exhibit a unique photophysical response to pH. These anilinomethylrhodamines (AnMR) maintain a colorless, nonfluorescent spirocyclic structure at high pH. The spirocyclic structures open in mildly acidic conditions and are weakly fluorescent; however, at very low pH, the fluorescence is greatly enhanced. The equilibrium constants of these processes show a linear response to substituent effects, which was demonstrated by the Hammett equation.

Isotope-labeling studies on the formation pathway of acrolein during heat processing of oils.

PubMed

Ewert, Alice; Granvogl, Michael; Schieberle, Peter

2014-08-20

Acrolein (2-propenal) is classified as a foodborne toxicant and was shown to be present in significant amounts in heated edible oils. Up to now, its formation was mainly suggested to be from the glycerol part of triacylglycerides, although a clear influence of the unsaturation of the fatty acid moiety was also obvious in previous studies. To unequivocally clarify the role of the glycerol and the fatty acid parts in acrolein formation, two series of labeled triacylglycerides were synthesized: [(13)C(3)]-triacylglycerides of stearic, oleic, linoleic, and linolenic acid and [(13)C(54)]-triacylglycerides with labeled stearic, oleic, and linoleic acid, but with unlabeled glycerol. Heating of each of the seven intermediates singly in silicon oil and measurement of the formed amounts of labeled and unlabeled acrolein clearly proved the fatty acid backbone as the key precursor structure. Enzymatically synthesized pure linoleic acid and linolenic acid hydroperoxides were shown to be the key intermediates in acrolein formation, thus allowing the discussion of a radical-induced reaction pathway leading to the formation of the aldehyde. Surprisingly, although several oils contained high amounts of acrolein after heating, deep-fried foods themselves, such as donuts or French fries, were low in the aldehyde.

Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways.

PubMed

Kerwin, Bruce A

2008-08-01

Polysorbates 20 and 80 (Tween 20 and Tween 80) are used in the formulation of biotherapeutic products for both preventing surface adsorption and as stabilizers against protein aggregation. The polysorbates are amphipathic, nonionic surfactants composed of fatty acid esters of polyoxyethylene sorbitan being polyoxyethylene sorbitan monolaurate for polysorbate 20 and polyoxyethylene sorbitan monooleate for polysorbate 80. The polysorbates used in the formulation of biopharmaceuticals are mixtures of different fatty acid esters with the monolaurate fraction of polysorbate 20 making up only 40-60% of the mixture and the monooleate fraction of polysorbate 80 making up >58% of the mixture. The polysorbates undergo autooxidation, cleavage at the ethylene oxide subunits and hydrolysis of the fatty acid ester bond. Autooxidation results in hydroperoxide formation, side-chain cleavage and eventually formation of short chain acids such as formic acid all of which could influence the stability of a biopharmaceutical product. Oxidation of the fatty acid moiety while well described in the literature has not been specifically investigated for polysorbate. This review focuses on the chemical structure of the polysorbates, factors influencing micelle formation and factors and excipients influencing stability and degradation of the polyoxyethylene and fatty acid ester linkages.

Lac-L-TTA, a novel lactose-based amino acid-sugar conjugate for anti-metastatic applications.

PubMed

Roviello, Giovanni N; Iannitti, Roberta; Palumbo, Rosanna; Simonyan, Hayarpi; Vicidomini, Caterina; Roviello, Valentina

2017-08-01

Here we describe the synthesis, chromatographic purification, MS and NMR characterization of a new lactosyl-derivative, i.e. a lactosyl thiophenyl-substituted triazolyl-thione L-alanine (Lac-L-TTA). This amino acid-sugar conjugate was prepared by solution synthesis in analogy to the natural fructosyl-amino acids. Furthermore, we investigated the inhibition of PC-3 prostate cancer cell colony formation by this lactose derivative in comparison with the less polar fructose-based derivative, Fru-L-TTA. This let us to compare the properties of the artificial derivative, object of the present work, with the monosaccharide-based counterpart and to obtain a preliminary information on the influence of polarity on such biological activity. A significantly higher anticancer effect of Lac-L-TTA with respect to the fructose analogue emerged from our study suggesting that the anti-metastatic potential of fructosyl-amino acids can be enhanced by increasing the polarity of the compounds, for example by introducing disaccharide moieties in place of fructose.

Naturally Occurring Cinnamic Acid Sugar Ester Derivatives.

PubMed

Tian, Yuxin; Liu, Weirui; Lu, Yi; Wang, Yan; Chen, Xiaoyi; Bai, Shaojuan; Zhao, Yicheng; He, Ting; Lao, Fengxue; Shang, Yinghui; Guo, Yu; She, Gaimei

2016-10-24

Cinnamic acid sugar ester derivatives (CASEDs) are a class of natural product with one or several phenylacrylic moieties linked with the non-anomeric carbon of a glycosyl skeleton part through ester bonds. Their notable anti-depressant and brains protective activities have made them a topic of great interest over the past several decades. In particular the compound 3',6-disinapoylsucrose, the index component of Yuanzhi (a well-known Traditional Chinese Medicine or TCM), presents antidepressant effects at a molecular level, and has become a hotspot of research on new lead drug compounds. Several other similar cinnamic acid sugar ester derivatives are reported in traditional medicine as compounds to calm the nerves and display anti-depression and neuroprotective activity. Interestingly, more than one third of CASEDs are distributed in the family Polygalaceae . This overview discusses the isolation of cinnamic acid sugar ester derivatives from plants, together with a systematic discussion of their distribution, chemical structures and properties and pharmacological activities, with the hope of providing references for natural product researchers and draw attention to these interesting compounds.

Imidazoline phosphonic acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redmore, D.

1972-07-04

Nitrogen-heterocyclic phosphonic acids and derivatives are characterized by aminomethyl (or substituted methyl) phosphonic acids or derivatives thereof bonded directly or indirectly, i.e., through a N-side chain to the nitrogen atom in the heterocyclic ring, for example those containing in the molecule at least one of the following units: ..pi..Equation/sup -/ where represents a heterocyclic ring having a nitrogen atom on the ring; -R'N- represents an amino- terminated side chain attached directly to the ring nitrogen (which side chain may or may not be present); and ..pi..Equation/sup -/ represents a methyl (or substituted methyl) phosphonic acid group where M is hydrogen,more » an alcohol or a salt moiety, and X and Y are hydrogen or a substituted group such as alkyl, aryl, etc., of which one or 2 units may be present depending on the available nitrogen bonded by hydrogens, and to uses for these compounds, for example, as scale inhibitors, corrosion inhibitors, etc. (5 claims)« less

Precursor ion scan driven fast untargeted screening and semi-determination of caffeoylquinic acid derivatives in Cynara scolymus L.

PubMed

Shen, Qing; Lu, Yanbin; Dai, Zhiyuan; Cheung, Hon-Yeung

2015-01-01

A precursor ion scan (PIS) technique based strategy was developed for rapid screening and semi-determination of caffeoylquinic acid derivatives (CADs) in artichoke (Cynara scolymus L.) using ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry. 1,5-Dicaffeoylquinic acid and 5-caffeoylquinic acid were used for studying the fragmentation behaviour of two classes of CADs, setting m/z 191 as a diagnostic moiety. When it was applied to artichoke sample, ten CADs were detected and elucidated in a single PIS run. Furthermore, method validation was implemented including: specificity (no interference), linearity (≥0.9993), limit of detection (LOD<0.12 ng mL(-1)) and limit of quantification (LOQ<0.25 ng mL(-1)), precision (RSD≤3.6), recovery (91.4-95.9%) and stability (at least 12 h). This approach was proven to be a powerful, selective and sensitive tool for rapid screening and semi-determination of untargeted components in natural products. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biotransformation of fluorophenyl pyridine carboxylic acids by the model fungus Cunninghamella elegans.

PubMed

Palmer-Brown, William; Dunne, Brian; Ortin, Yannick; Fox, Mark A; Sandford, Graham; Murphy, Cormac D

2017-09-01

1. Fluorine plays a key role in the design of new drugs and recent FDA approvals included two fluorinated drugs, tedizolid phosphate and vorapaxar, both of which contain the fluorophenyl pyridyl moiety. 2. To investigate the likely phase-I (oxidative) metabolic fate of this group, various fluorinated phenyl pyridine carboxylic acids were incubated with the fungus Cunninghamella elegans, which is an established model of mammalian drug metabolism. 3.  19 F NMR spectroscopy established the degree of biotransformation, which varied depending on the position of fluorine substitution, and gas chromatography-mass spectrometry (GC-MS) identified alcohols and hydroxylated carboxylic acids as metabolites. The hydroxylated metabolites were further structurally characterised by nuclear magnetic resonance spectroscopy (NMR), which demonstrated that hydroxylation occurred on the 4' position; fluorine in that position blocked the hydroxylation. 4. The fluorophenyl pyridine carboxylic acids were not biotransformed by rat liver microsomes and this was a consequence of inhibitory action, and thus, the fungal model was crucial in obtaining metabolites to establish the mechanism of catabolism.

PQQ: Biosynthetic studies in Methylobacterium AM1 and Hyphomicrobium X using specific TC labeling and NMR. [Pyrroloquinoline quinones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Houck, D.R.; Hanners, J.L.; Unkefer, C.J.

Using TC labeling and NMR spectroscopy we have determined biosynthetic precursors of pyrroloquinoline quinone (PQQ) in two closely related serine-type methylotrophs, Methylobacterium AM1 and Hyphomicrobium X. Analysis of the TC-labeling data revealed that PQQ is constructed from two amino acids: the portion containing N-6, C-7,8,9 and the two carboxylic acid groups, C-7' and 9', is derived-intact-from glutamate. The remaining portion is derived from tyrosine; the phenol side chain provides the six carbons of the ring containing the orthoquinone, whereas internal cyclization of the amino acid backbone forms the pyrrole-2-carboxylic acid moiety. This is analogous to the cyclization of dopaquinone tomore » form dopachrome. Dopaquinone is a product of the oxidation of tyrosine (via dopa) in reactions catalyzed by monophenol monooxygenase (EC 1.14.18.1). Starting with tyrosine and glutamate, we will discuss possible biosynthetic routes to PQQ. 29 refs., 4 figs., 2 tabs.« less

Two enzyme immunoassays to screen for 2,4-dichlorophenoxyacetic acid in water.

PubMed

Fleeker, J

1987-01-01

Two solid-phase enzyme immunoassays were developed to measure 2,4-dichlorophenoxyacetic acid (2,4-D), using 2 sets of structurally distinct immunogens and enzyme ligands. The 2,4-D analog, 2-methyl-4-chlorophenoxyacetic acid (MCPA), gave a similar response with both methods, whereas other phenoxy herbicides cross-reacted differently. In method A, the aromatic moiety of 2,4-D was distal from the carrier protein and labeled enzyme, whereas in method B, the acetic acid portion of the herbicide was distal. The use of both methods to screen for this herbicide in ground water and municipal and river water reduced the number of false-positive responses. Water sources having a low background response could be monitored with either method alone. When a concentration step, with disposable C18 extraction columns, was used, the limit of sensitivity was 5 micrograms/L. Method A was the more sensitive of the 2 methods with a limit of detection of 10 micrograms/L without the concentration step.

Mitochondrial biotransformation of ω-(phenoxy)alkanoic acids, 3-(phenoxy)acrylic acids, and ω-(1-methyl-1H-imidazol-2-ylthio)alkanoic acids: A prodrug strategy for targeting cytoprotective antioxidants to mitochondria

PubMed Central

Roser, Kurt S.; Brookes, Paul S.; Wojtovich, Andrew P.; Olson, Leif P.; Shojaie, Jalil; Parton, Richard L.; Anders, M. W.

2010-01-01

Mitochondrial reactive oxygen species (ROS) generation and the attendant mitochondrial dysfunction are implicated in a range of disease states. The objective of the present studies was to test the hypothesis that the mitochondrial β-oxidation pathway could be exploited to deliver and biotransform the prodrugs ω-(phenoxy)alkanoic acids, 3-(phenoxy)acrylic acids, and ω-(1-methyl-1H-imidazol-2-ylthio)alkanoic acids to the corresponding phenolic antioxidants or methimazole. 3 -and 5-(Phenoxy)alkanoic acids and methyl-substituted analogs were biotransformed to phenols; rates of biotransformation decreased markedly with methyl-group substitution on the phenoxy moiety. 2,6-Dimethylphenol formation from the analogs 3-([2,6-dimethylphenoxy]methylthio)propanoic acid and 3-(2,6-dimethylphenoxy)acrylic acid was greater than that observed with ω-(2,6-dimethylphenoxy)alkanoic acids. 3- and 5-(1-Methyl-1H-imidazol-2-ylthio)alkanoic acids were rapidly biotransformed to the antioxidant methimazole and conferred significant cytoprotection against hypoxia-reoxygenation injury in isolated cardiomyocytes. Both 3-(2,6-dimethylphenoxy)propanoic acid and 3-(2,6-dimethylphenoxy)acrylic acid also afforded cytoprotection against hypoxia-reoxygenation injury in isolated cardiomyocytes. These results demonstrate that mitochondrial β-oxidation is a potentially useful delivery system for targeting antioxidants to mitochondria. PMID:20129794

Multifunctional PEG-carboxylate copolymer coated superparamagnetic iron oxide nanoparticles for biomedical application

NASA Astrophysics Data System (ADS)

Illés, Erzsébet; Szekeres, Márta; Tóth, Ildikó Y.; Szabó, Ákos; Iván, Béla; Turcu, Rodica; Vékás, Ladislau; Zupkó, István; Jaics, György; Tombácz, Etelka

2018-04-01

Biocompatible magnetite nanoparticles (MNPs) were prepared by post-coating the magnetic nanocores with a synthetic polymer designed specifically to shield the particles from non-specific interaction with cells. Poly(ethylene glycol) methyl ether methacrylate (PEGMA) macromonomers and acrylic acid (AA) small molecular monomers were chemically coupled by quasi-living atom transfer radical polymerization (ATRP) to a comb-like copolymer, P(PEGMA-co-AA) designated here as P(PEGMA-AA). The polymer contains pendant carboxylate moieties near the backbone and PEG side chains. It is able to bind spontaneously to MNPs; stabilize the particles electrostatically via the carboxylate moieties and sterically via the PEG moieties; provide high protein repellency via the structured PEG layer; and anchor bioactive proteins via peptide bond formation with the free carboxylate groups. The presence of the P(PEGMA-AA) coating was verified in XPS experiments. The electrosteric (i.e., combined electrostatic and steric) stabilization is efficient down to pH 4 (at 10 mM ionic strength). Static magnetization and AC susceptibility measurements showed that the P(PEGMA-AA)@MNPs are superparamagnetic with a saturation magnetization value of 55 emu/g and that both single core nanoparticles and multicore structures are present in the samples. The multicore components make our product well suited for magnetic hyperthermia applications (SAR values up to 17.44 W/g). In vitro biocompatibility, cell internalization, and magnetic hyperthermia studies demonstrate the excellent theranostic potential of our product.

A ruthenium dimer complex with a flexible linker slowly threads between DNA bases in two distinct steps.

PubMed

Bahira, Meriem; McCauley, Micah J; Almaqwashi, Ali A; Lincoln, Per; Westerlund, Fredrik; Rouzina, Ioulia; Williams, Mark C

2015-10-15

Several multi-component DNA intercalating small molecules have been designed around ruthenium-based intercalating monomers to optimize DNA binding properties for therapeutic use. Here we probe the DNA binding ligand [μ-C4(cpdppz)2(phen)4Ru2](4+), which consists of two Ru(phen)2dppz(2+) moieties joined by a flexible linker. To quantify ligand binding, double-stranded DNA is stretched with optical tweezers and exposed to ligand under constant applied force. In contrast to other bis-intercalators, we find that ligand association is described by a two-step process, which consists of fast bimolecular intercalation of the first dppz moiety followed by ∼10-fold slower intercalation of the second dppz moiety. The second step is rate-limited by the requirement for a DNA-ligand conformational change that allows the flexible linker to pass through the DNA duplex. Based on our measured force-dependent binding rates and ligand-induced DNA elongation measurements, we are able to map out the energy landscape and structural dynamics for both ligand binding steps. In addition, we find that at zero force the overall binding process involves fast association (∼10 s), slow dissociation (∼300 s), and very high affinity (Kd ∼10 nM). The methodology developed in this work will be useful for studying the mechanism of DNA binding by other multi-step intercalating ligands and proteins. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Incorporation of a Doubly Functionalized Synthetic Amino Acid into Proteins for Creating Chemical and Light-Induced Conjugates.

PubMed

Yamaguchi, Atsushi; Matsuda, Takayoshi; Ohtake, Kazumasa; Yanagisawa, Tatsuo; Yokoyama, Shigeyuki; Fujiwara, Yoshihisa; Watanabe, Takayoshi; Hohsaka, Takahiro; Sakamoto, Kensaku

2016-01-20

Z-Lysine (ZLys) is a lysine derivative with a benzyloxycarbonyl group linked to the ε-nitrogen. It has been genetically encoded with the UAG stop codon, using the pair of an engineered variant of pyrrolysyl-tRNA synthetase (PylRS) and tRNA(Pyl). In the present study, we designed a novel Z-lysine derivative (AmAzZLys), which is doubly functionalized with amino and azido substituents at the meta positions of the benzyl moiety, and demonstrated its applicability for creating protein conjugates. AmAzZLys was incorporated into proteins in Escherichia coli, by using the ZLys-specific PylRS variant. AmAzZLys was then site-specifically incorporated into a camelid single-domain antibody specific to the epidermal growth factor receptor (EGFR). A one-pot reaction demonstrated that the phenyl amine and azide were efficiently linked to the 5 kDa polyethylene glycol and a fluorescent probe, respectively, through specific bio-orthogonal chemistry. The antibody was then tested for the ability to form a photo-cross-link between its phenylazide moiety and the antigen, while the amino group on the same ring was used for chemical labeling. When incorporated at a selected position in the antibody and exposed to 365 nm light, AmAzZLys formed a covalent bond with the EGFR ectodomain, with the phenylamine moiety labeled fluorescently prior to the reaction. The present results illuminated the versatility of the ZLys scaffold, which can accommodate multiple reactive groups useful for protein conjugation.

Molecular characterization of co-transcribed genes from Streptomyces tendae Tü901 involved in the biosynthesis of the peptidyl moiety of the peptidyl nucleoside antibiotic nikkomycin.

PubMed

Bruntner, C; Lauer, B; Schwarz, W; Möhrle, V; Bormann, C

1999-08-01

Six genes (nikA, nikB, nikD, nikE, nikF, and nikG) from Streptomyces tendae Tü901 were identified by sequencing the region surrounding the nikC gene, which encodes L-lysine 2-aminotransferase, previously shown to catalyze the initial reaction in the biosynthesis of hydroxypyridylhomothreonine, the peptidyl moiety of the peptidyl nucleoside antibiotic nikkomycin. These genes, together with the nikC gene, span a DNA region of 7.87 kb and are transcribed as a polycistronic mRNA in a growth-phase dependent manner. The sequences of the deduced proteins NikA and NikB exhibit significant similarity to those of acetaldehyde dehydrogenases and 4-hydroxy-2-oxovalerate aldolases, respectively, which are involved in meta-cleavage degradation of aromatic hydrocarbons. The predicted NikD gene product shows sequence similarity to monomeric sarcosine oxidases, and the deduced NikE protein belongs to the superfamily of adenylate-forming enzymes. The nikF gene and the nikG gene encode a cytochrome P450 monooxygenase and a ferredoxin, respectively. Disruption of any of the genes nikA, nikB, nikD, nikE and nikF by insertion of a kanamycin resistance cassette abolished formation of the biologically active nikkomycins I, J, X, and Z. The nikA, nikB, nikD, and nikE mutants accumulated the nucleoside moieties nikkomycins Cx and Cz. In the nikD and nikE mutants nikkomycin production (nikkomycins I, J, X, Z) could be restored by feeding with picolinic acid and hydroxypyridylhomothreonine, respectively. The nikF mutant exclusively produced novel derivatives, nikkomycins Lx and Lz, which contain pyridylhomothreonine as the peptidyl moiety. Our results indicate that the nikA, nikB, nikD, nikE, nikF, and nikG genes, in addition to nikC, function in the biosynthetic pathway leading to hydroxypyridylhomothreonine, the putative activities of each of their products are discussed.

The 4-pyridylmethyl ester as a protecting group for glutamic and aspartic acids: 'flipping' peptide charge states for characterization by positive ion mode ESI-MS.

PubMed

Garapati, Sriramya; Burns, Colin S

2014-03-01

Use of the 4-pyridylmethyl ester group for side-chain protection of glutamic acid residues in solid-phase peptide synthesis enables switching of the charge state of a peptide from negative to positive, thus making detection by positive ion mode ESI-MS possible. The pyridylmethyl ester moiety is readily removed from peptides in high yield by hydrogenation. Combining the 4-pyridylmethyl ester protecting group with benzyl ester protection reduces the number of the former needed to produce a net positive charge and allows for purification by RP HPLC. This protecting group is useful in the synthesis of highly acidic peptide sequences, which are often beset by problems with purification by standard RP HPLC and characterization by ESI-MS. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

Phosphatidylglycerol Synthesis in Spinach Chloroplasts: Characterization of the Newly Synthesized Molecule

PubMed Central

Sparace, Salvatore A.; Mudd, J. Brian

1982-01-01

Intact chloroplasts from spinach (Spinacia oleracea L., hybrid 424) readily incorporate [14C]glycerol-3-phosphate and [14C]acetate into diacylglycerol, monoacylglycerol, diacylglycrol, free fatty acids (only when acetate is the precursor), phosphatidic acid, phosphatidylcholine, and most notably phosphatidylglycerol. The fraction of phosphatidylglycerol synthesized is greatly increased by the presence of manganese chloride in the reaction mixture. Glycerol-3-phosphate-labeled phosphatidylglycerol is equally labeled in the two glycerol moieties of the molecule. Acetate-labeled phosphatidylglycerol is equally labeled in both acyl groups. Position one contains primarily oleate, linoleate and small amounts of palmitate. Position two contains primarily palmitate. No radioactive trans-Δ3-hexadecenoate was detected. The labeling patterns indicate that the radioactive phosphatidylglycerol is the product of de novo chloroplast lipid biosynthesis and furthermore, phosphatidylglycerol may be a substrate for fatty acid desaturation. Images Fig. 1 PMID:16662664