|
| ||
|
|
||
Acid Moiety (acid + moiety)
Kinds of Acid Moiety Selected AbstractsSynthesis and Proinflammatory Properties of Muramyl Tripeptides Containing Lysine and Diaminopimelic Acid MoietiesCHEMBIOCHEM, Issue 11 2005Abhijit Roychowdhury Dr. Abstract The unusual amino acid diaminopimelic acid (DAP) was prepared by cross metathesis of appropriately protected vinyl glycine and allyl glycine derivatives. Catalytic hydrogenation of the cross-coupling product resulted in reduction of the double bond and the removal of protecting groups. The resulting compounds were appropriately protected for the polymer-supported and solution-phase synthesis of muramyl tripeptides 2 and 3, which differ in the amidation of the ,-carboxylic acids of the isoglutamine and DAP moieties. Muramyl dipeptide (1, MDP), the DAP-containing muramyl tripeptide 3, and the lysine-containing muramyl tripeptides 4 and 5 induced TNF-, gene expression without TNF-, protein production in a human monocytic cell line. The observed block in translation could be removed by co-incubation with LPS, resulting in an apparent synergistic effect. Compound 2 did not induce TNF-, gene expression, neither did it exhibit a synergistic effect with LPS; this indicates that amidation of the ,-carboxylic acids of the isoglutamine and DAP moieties results in a loss of biological activity. It is proposed that amidation of ,-carboxylic acids is a strategy that may be used by pathogens to avoid detection by the innate immune system. Furthermore, the pattern recognition receptors Nod1 and Nod2 have been implicated in the possible induction of a synergistic effect of muropeptides with LPS. [source] Template Synthesis of Peptidomimetics Composed of Aspartic Acid Moiety by Ugi Four-Component Condensation Reaction.CHEMINFORM, Issue 49 2005Xin Zhang Abstract For Abstract see ChemInform Abstract in Full Text. [source] Lipophilic methotrexate conjugates with glucose-lipoamino acid moieties: Synthesis and in vitro antitumor activityDRUG DEVELOPMENT RESEARCH, Issue 3 2001Rosario Pignatello Abstract To obtain methotrexate (MTX) derivatives with a balanced hydrolipophilic character, we synthesized a series of conjugates in which the drug was linked to lipoamino acid (LAA)-glucose residues (LAAG-MTX). These conjugates displayed increased solubility in polar media compared with the corresponding LAA-MTX conjugates previously described. In vitro biological testing of LAAG-MTX indicated that the introduction of the sugar moiety decreased the biological activity of these MTX conjugates. The tetradecyl derivative 6b, however, was effective in inhibiting the dihydrofolate reductase activity in vitro and showed an inhibitory effect on human lymphoblastoid cell growth. Drug Dev. Res. 52:454,461, 2001. © 2001 Wiley-Liss, Inc. [source] Synthesis, and Helix or Hairpin-Turn Secondary Structures of ,Mixed' ,/, -Peptides Consisting of Residues with Proteinogenic Side Chains and of 2-Amino-2-methylpropanoic Acid (Aib)HELVETICA CHIMICA ACTA, Issue 9 2006Dieter Seebach Abstract Twelve peptides, 1,12, have been synthesized, which consist of alternating sequences of , - and , -amino acid residues carrying either proteinogenic side chains or geminal dimethyl groups (Aib). Two peptides, 13 and 14, containing 2-methyl-3-aminobutanoic acid residues or a ,random mix' of ,-, ,2 -, and ,3 -amino acid moieties were also prepared. The new compounds were fully characterized by CD (Figs.,1 and 2), and 1H- and 13C-NMR spectroscopy, and high-resolution mass spectrometry (HR-MS). In two cases, 3 and 14, we discovered novel types of turn structures with nine- and ten-membered H-bonded rings forming the actual turns. In two other cases, 8 and 11, we found 14/15 -helices, which had been previously disclosed in mixed ,/, -peptides containing unusual , -amino acids with non-proteinogenic side chains. The helices are formed by peptides containing the amino acid moiety Aib in every other position, and their backbones are primarily not held together by H-bonds, but by the intrinsic conformations of the containing amino acid building blocks. The structures offer new possibilities of mimicking peptide,protein and protein,protein interactions (PPI). [source] A Polymersome Nanoreactor with Controllable Permeability Induced by Stimuli-Responsive Block CopolymersADVANCED MATERIALS, Issue 27 2009Kyoung Taek Kim A method to generate and control the permeability of polymersome membranes using mixtures of amphiphilic and stimuli-responsive boronic acid-containing block copolymers is reported. The latter block copolymers form phase-separated domains in the polymersomes, which can be dissolved by increasing the pH of the medium or by introducing sugar molecules that covalently bind to the boronic acid moieties. [source] Enlarging the library of poly-(L -lysine citramide) polyelectrolytic drug carriersJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 20 2001Anne-Claude Couffin-Hoarau Abstract Poly-(L -lysine citramide) is a degradable drug carrier of the polyelectrolyte type that is composed of citric acid and L -lysine building blocks. In a previous work, poly-(L -lysine citramide) was synthesized by the interfacial polycondensation of ,-hydroxy acid protected citryl dichloride with COOH-protected lysine diamine. Because of head-to-head and head-to-tail and tail-to-tail linkages in the chains as well as various side reactions such as deprotection of the ,-hydroxy acid moieties and intramolecular imide ring formation, a very large family of degradable polyelectrolyte copolymers was obtained. All the members of this family hydrolytically degrade to the same end products. In this study, another route was explored based on the polycondensation of ,-hydroxy acid protected citric acid pentafluorophenyl diesters, namely, citrobenzal dipentafluorophenyl and citrochloral dipentafluorophenyl with N - N,-trimethylsilylated COOH-protected L -lysine. The resulting polymers were characterized by IR, NMR, and size exclusion chromatographic analyses. The resulting chain structures and repeat units were identified from these characterizations and are discussed as compared with characteristics exhibited by analogous polymers resulting from interfacial polycondensation. Differences observed at the intermediate stage involving protected polymers were largely erased during the final deprotection stage because of imide formation during final hydrolysis under the selected conditions. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3475,3484, 2001 [source] Efficacy of various pyrethroid structures against a highly metabolically resistant isogenic strain of Helicoverpa armigera (Lepidoptera: Noctuidae) from ChinaPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 10 2007Jianguo Tan Abstract BACKGROUND: Resistance to pyrethroids and other types of insecticides in Helicoverpa armigera (Hübner) has been documented in many countries. The isolation of specific resistance mechanisms in isogenic strains is an optimal approach to investigate cross-resistance pattern, and to validate resistance breaking pyrethroids. In this study an isogenic metabolic resistance CMR strain was successfully isolated from a field pyrethroid-resistant population of H. armigera. With this strain, cross-resistance among 19 pyrethroid insecticides with varying chemical structures was analysed. RESULTS: Resistance to pyrethroids in the CMR strain was likely to be due to enhanced oxidative metabolism. The most significant cross-resistance in the CMR strain was between pyrethroids such as fenvalerate, tau-fluvalinate and flumethrin characterised by having both phenoxybenzyl and aromatic acid moieties. Substitution of the phenoxybenzyl group with a polyfluorobenzyl group, as in tefluthrin, benfluthrin and transfluthrin, overcame most of this resistance. CONCLUSION: The findings in this study support the assertion that it is possible to find pyrethroids that are active against resistant populations. Such pyrethroids could be considered as possible partners or resistance breaking pyrethroids in a pyrethroid resistance management programme for H. armigera in China and in other Asian countries where the oxidative metabolism resistance is a dominant mechanism. Copyright © 2007 Society of Chemical Industry [source] NMR and UPLC-qTOF-MS/MS characterisation of novel phenylethanol derivatives of phenylpropanoid glucosides from the leaves of strawberry (Fragaria × ananassa cv. Jonsok)PHYTOCHEMICAL ANALYSIS, Issue 5 2009Kati Hanhineva Abstract Introduction Strawberry (Fragaria × ananassa) is rich in polyphenols, particularly anthocyanins, flavonols, condensed tannins and ellagic tannins. In addition to the fruits, the leaves of strawberry also contain a wide range of phenolic compound classes, but have not been investigated to the same extent as the fruit. Objective To characterise a metabolite group present in the leaves of strawberry, that was not amenable for identification based on earlier information available in the literature. Methodology Methanolic extracts of strawberry leaves were analysed by UPLC-qTOF-MS/MS and iterative quantum mechanical NMR spectral analysis. Results The structures of phenylethanol derivatives of phenylpropanoid glucosides Eutigoside A ( F4) and its two isomeric forms 2-(4-hydroxyphenyl)ethyl-[6- O -(Z)-coumaroyl]- ,- d -glucopyranoside ( F6) and 4-(2-hydroxyethyl)phenyl-[6- O -(e)-coumaroyl]- ,- d -glucopyranoside ( F1) were resolved by NMR and UPLC-qTOF-MS/MS. In addition, two other derivatives of phenylpropanoid glucosides similar to Eutigoside A but possessing different phenolic acid moieties, namely Grayanoside A ( F5) and 2-(4-hydroxyphenyl)ethyl-[6- O -(e)-caffeoyl]- ,- d -glucopyranoside ( F14), were similarly identified. Also, accurate characteristic coupling constants for the subunits are reported and their usefulness in structural analysis is highlighted. Conclusion Chemical analysis of the leaves of strawberry (Fragaria × ananassa cv. Jonsok) resulted in the identification of a compound class, phenylethanol derivatives of phenylpropanoid glycosides, not previously found in strawberry. Copyright © 2009 John Wiley & Sons, Ltd. [source] Methylation of acidic moieties in poly(methyl methacrylate-co-methacrylic acid) copolymers for end-group characterization by tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 14 2010Rémi Giordanengo The complete structural characterization of a copolymer composed of methacrylic acid (MAA) and methyl methacrylate (MMA) units was achieved using tandem mass spectrometry. In a first step, collision-induced dissociation (CID) of sodiated MAA-MMA co-oligomers allowed us to determine the co-monomeric composition, the random nature of the copolymer and the sum of the end-group masses. However, dissociation reactions of MAA-based molecules mainly involve the acidic pendant groups, precluding individual characterization of the end groups. Therefore, methylation of all the acrylic acid moieties was performed to transform the MAA-MMA copolymer into a PMMA homopolymer, for which CID mainly proceeds via backbone cleavages. Using trimethylsilyldiazomethane as a derivatization agent, this methylation reaction was shown to be complete without affecting the end groups. Using fragmentation rules established for PMMA polymers together with accurate mass measurements of the product ions and knowledge of reagents used for the studied copolymer synthesis, a structure could be proposed for both end groups and it was found to be consistent with signals obtained in nuclear magnetic resonance spectra. Copyright © 2010 John Wiley & Sons, Ltd. [source] Hexane-1,6-diaminium chloride [hydrogen bis(chloroacetate)]ACTA CRYSTALLOGRAPHICA SECTION C, Issue 11 2009Agnieszka Paul In the structure of the title compound, C6H18N22+·H(C2H2ClO2)2,·Cl,, the hexane-1,6-diaminium dication is disordered over two sets of positions, with almost equal occupancies. Both alternative positions of the dication are in the fully extended conformation, situated on an inversion centre at (, , ). Two chloroacetic acid moieties, related by another centre of symmetry at (, , ), are connected by a very short symmetrical O...H...O hydrogen bond [O...O = 2.452,(2),Å], with the H atom at the centre of inversion. These two fragments thus effectively form the hydrogen bis(chloroacetate) monoanion, and the overall charge is balanced by an additional chloride anion which resides on a twofold axis. The ions form a layer structure, with alternating layers of dications and anions running along the [101] direction, linked via hydrogen bonds. There are two N,H...O interactions and two N,H...Cl, interactions. [source] Defining the glycophenotype of squamous epithelia using plant and mammalian lectins.APMIS, Issue 12 20023-linked N-acetylneuraminic acid in squamous epithelia, Differentiation-dependent expression of, carcinomas, its differential effect on binding of the endogenous lectins galectins- A thorough characterization of the properties of squamous epithelial cells is necessary in order to improve our understanding of the functional aspects of normal development and malignant aberrations. Up to now, studies have focused almost exclusively on monitoring distinct protein markers. With our growing awareness of the coding function of glycan chains of cellular glycoconjugates and their interaction with receptors (lectins) in situ, defining the glycophenotype of these cells has become an important issue. Whereas the commonly applied plant lectins are tools used to map the presence and localization of biochemically defined saccharide epitopes, the introduction of endogenous (mammalian) lectins to this analysis enables us to take the step from monitoring the presence of glycan to understanding the functional implications by revealing ligand properties of the detected epitope for tissue lectin. Thus, in this study we investigated a distinct aspect of glycosylation using plant and mammalian lectins, i.e. the linkage type of sialylation. We first mapped the expression profile of the type of sialylation (,2,3- or ,2,6-linked) by plant lectins. Based on the hypothesis that this factor regulates accessibility of ligands for endogenous lectins we introduced two labeled galectins to this study. Galectin-3 (but not galectin-1) binding was related to cell differentiation in normal adult and developing epithelia, cultured epidermal cells, and carcinomas derived from these epithelia. The presented data suggest that ,2,6-linked N-acetyl- D -neuraminic acid moieties could serve to mask galectin-3-reactive glycoepitopes. As a consequence, monitoring of the linkage type of sialic acid in glycans by plant lectins therefore has implications for the extent of glycan reactivity with endogenous lectins, pointing to a potential function of changes in sialylation type beyond these cell and lectin systems. [source] Biosynthesis of fatty acid amide elicitors of plant volatiles by insect herbivores ,ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 2 2005James H. Tumlinson Larvae of several species of Lepidoptera produce fatty acid amide elicitors that induce the plants on which they feed to synthesize and release volatile organic compounds. The volatiles released by the plants act as cues that aid in host location by natural enemies of the herbivorous larvae. The elicitors are synthesized in the larvae by enzymes embedded in the membranes of the crop and anterior midgut tissues. The fatty acid precursors of the elicitors are obtained from the plants on which the caterpillars feed, while the amino acid moieties appear to be obtained from pools within the insects. The fatty acid amide elicitors are rapidly hydrolyzed in the midgut and hindgut by enzymes in the gut lumen. The role of these fatty acid amides in caterpillar metabolism is not yet understood. Arch. Insect Biochem. Physiol. 58:54,68, 2005. © 2005 Wiley-Liss, Inc. [source] The Proteolytic Stability of ,Designed' , -Peptides Containing , -Peptide-Bond Mimics and of Mixed ,,, -Peptides: Application to the Construction of MHC-Binding PeptidesCHEMISTRY & BIODIVERSITY, Issue 5 2005David Whereas , -peptides are rapidly degraded in vivo and in vitro by a multitude of peptidases, substrates constructed entirely of or incorporating homologated , -amino acid (i.e., , -amino acid) units exhibit a superior stability profile. Efforts made so far to proteolytically hydrolyze a ,, peptide bond have not proved fruitful; a study aimed at breaching this proteolytic stability is discussed here. A series of such bonds have been designed with side-chain groups similar in relative positions (constitution) and three-dimensional arrangements (configuration) as found about , -peptidic amide bonds. Increasing the prospect for degradation would permit the tuning of , -peptide stability; here, however, no cleavage was observed (1, 2, 4,6, Table,1). Peptides comprised of , - and , -amino acids (mixed ,,, -peptides, 8,11) are expected to benefit from both recognition by a natural receptor and a high level of proteolytic stability, ideal characteristics of pharmacologically active compounds. ,3 -Peptides containing , -amino acid moieties at the N-terminus are degraded, albeit slowly, by several peptidases. Of particular interest is the ability of pronase to cleave an ,, peptide bond, namely that of ,Ala,3hAla. Significantly, successful hydrolysis is independent of the configuration of the , -amino acid. Some of the ,,, -peptides discussed here are being investigated for their binding affinities to class I MHC proteins. The computer-programming steps required to prepare ,,, -peptides on an automated peptide synthesizer are presented. [source] The World of , - and , -Peptides Comprised of Homologated Proteinogenic Amino Acids and Other ComponentsCHEMISTRY & BIODIVERSITY, Issue 8 2004Dieter Seebach The origins of our nearly ten-year research program of chemical and biological investigations into peptides based on homologated proteinogenic amino acids are described. The road from the biopolymer poly[ethyl (R)-3-hydroxybutanoate] to the , -peptides was primarily a step from organic synthesis methodology (the preparation of enantiomerically pure compounds (EPCs)) to supramolecular chemistry (higher-order structures maintained through non-covalent interactions). The performing of biochemical and biological tests on the , - and , -peptides, which differ from natural peptides/proteins by a single or two additional CH2 groups per amino acid, then led into bioorganic chemistry and medicinal chemistry. The individual chapters of this review article begin with descriptions of work on , -amino acids, , -peptides, and polymers (Nylon-3) that dates back to the 1960s, even to the times of Emil Fischer, but did not yield insights into structures or biological properties. The numerous, often highly physiologically active, or even toxic, natural products containing ,- and ,-amino acid moieties are then presented. Chapters on the preparation of homologated amino acids with proteinogenic side chains, their coupling to provide the corresponding peptides, both in solution (including thioligation) and on the solid phase, their isolation by preparative HPLC, and their characterization by mass spectrometry (HR-MS and MS sequencing) follow. After that, their structures, predominantly determined by NMR spectroscopy in methanolic solution, are described: helices, pleated sheets, and turns, together with stack-, crankshaft-, paddlewheel-, and staircase-like patterns. The presence of the additional CC bonds in the backbones of the new peptides did not give rise to a chaotic increase in their secondary structures as many protein specialists might have expected: while there are indeed more structure types than are observed in the , -peptide realm , three different helices (10/12 -, 12 -, and 14 -helix) if we include oligomers of trans -2-aminocyclopentanecarboxylic acid, for example , the structures are already observable with chains made up of only four components, and, having now undergone a learning process, we are able to construct them by design. The structures of the shorter , -peptides can also be reliably determined by molecular-dynamics calculations (in solution; GROMOS program package). Unlike in the case of the natural helices, these compounds' folding into secondary structures is not cooperative. In , - and , -peptides, it is possible to introduce heteroatom substituents (such as halogen or OH) onto the backbones or to incorporate heteroatoms (NH, O) directly into the chain, and, thanks to this, it has been possible to study effects unobservable in the world of the , -peptides. Tests with proteolytic enzymes of all types (from mammals, microorganisms, yeasts) and in vivo examination (mice, rats, insects, plants) showed , - and , -peptides to be completely stable towards proteolysis and, as demonstrated for two , -peptides, extraordinarily stable towards metabolism, even when bearing functionalized side chains (such as those of Thr, Tyr, Trp, Lys, or Arg). The , -peptides so far examined also normally display no or only very weak cytotoxic, antiproliferative, antimicrobial, hemolytic, immunogenic, or inflammatory properties either in cell cultures or in vivo. Even biological degradation by microbial colonies of the types found in sewage-treatment plants or in soil is very slow. That there are indeed interactions of ,- and ,-peptides with biological systems, however, can be seen in the following findings: i) organ-specific distribution takes place after intravenous (i.v.) administration in rats, ii) transport through the intestines of rodents has been observed, iii) , -peptides with positively charged side chains (Arg and Lys) settle on cell surfaces, are able to enter into mammalian cells (fibroplasts, keratinocytes, HeLa cells), and migrate into their cell nuclei (and nucleoli), and iv) in one case, it has already been established that a , -peptide derivative can up- and down-regulate gene expression rates. Besides these less sharply definable interactions, it has also been possible to construct , - and , -peptide agonists of naturally occurring peptide hormones, MHC-binding , -peptides, or amphipathic , -peptide inhibitors of membrane-bound proteins in a controlled fashion. Examples include somatostatin mimics and the suppression of cholesterol transport through the intestinal brush-border membrane (by the SR-BI-protein). The results so far obtained from investigations into peptides made up of homologues of the proteinogenic amino acids also represent a contribution to deepening of our knowledge of the natural peptides/proteins, while potential for biomedicinal application of this new class of substances has also been suggested. [source] Asymmetry Induction by Cooperative Intermolecular Hydrogen Bonds in Surface-Anchored Layers of Achiral Molecules,CHEMPHYSCHEM, Issue 10 2006Alexandre Dmitriev Dr. Abstract The mesoscale induction of two-dimensional supramolecular chirality (formation of 2D organic domains with a single handedness) was achieved by self-assembly of 1,2,4-benzenetricarboxylic (trimellitic) acid on a Cu(100) surface at elevated temperatures. The combination of spectroscopic [X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS)], real-space-probe [scanning tunneling microscopy (STM)], and computational [density functional theory (DFT)] methods allows a comprehensive characterization of the obtained organic adlayers, where details of molecular adsorption geometry, intermolecular coupling, and surface chemical bonding are elucidated. The trimellitic acid species, comprising three functional carboxylic groups, form distinct stable mirror-symmetric hydrogen-bonded domains. The chiral ordering is associated with conformational restriction in the domains: molecules anchor to the substrate with an ortho carboxylate group, providing two para carboxylic acid moieties for collective lateral interweaving through H bonding, which induces a specific tilt of the molecular plane. The ease of molecular symmetry switching in domain formation makes homochiral-signature propagation solely limited by the terrace width. The molecular layer modifies the morphology of the underlying copper substrate and induces ,m-sized strictly homochiral terraces. [source] Inorganic Drug-Delivery Nanovehicle Conjugated with Cancer-Cell-Specific LigandADVANCED FUNCTIONAL MATERIALS, Issue 10 2009Jae-Min Oh Abstract The surface of layered double hydroxide nanoparticles, a potential drug-delivery nanovehicle, is modified with the cancer-cell-specific ligand, folic acid. The surface modification is successfully accomplished through step-by-step coupling reactions with aminopropyltriethoxysilane and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide. In order to evaluate the cancer-cell targeting effect of folic-acid-grafted layered double hydroxide utilizing fluorescence-related assay, both layered double hydroxide with and without folic acid moiety are labeled with fluorescein 5,-isothiocyanate. The uptake of layered double hydroxide and folic acid conjugated into KB and A549 cells is visualized using fluorescence microscopy and measured by flow cytometry. Both chemical and biological assay results demonstrate that the folic acid molecules are indeed conjugated to the surface of layered double hydroxide and thus the selectivity of nanovehicles to cancer cells overexpressing folate receptors increases. In this study, it is suggested that layered double hydroxide nanoparticles can be used as drug-delivery carriers with a targeting function due to the chemical conjugation with specific ligand. [source] Synthesis of the Antibiotic (R)-Reutericyclin via Dieckmann CondensationHELVETICA CHIMICA ACTA, Issue 11 2005Roswitha Böhme (R)-Reutericyclin ((R)- 1), a bactericidal, amphiphilic natural product with a trisubstituted tetramic acid moiety, was prepared in four steps from D -leucine in an overall yield of 24%. The chiral heterocyclic portion of 1 was synthesized by Dieckmann cyclization of ethyl N -(acetoacetyl)leucinate (7), and the resulting pyrrole derivative 8 was N -acylated with (E)-dec-2-enoyl chloride in the presence of BuLi at ,,70° (Scheme,2). This new procedure is straightforward and allows the synthesis of both antipodes of reutericyclin in an enantiomeric excess (ee) of ca. 80%. [source] Practical [14C]-synthesis of molecules containing an acetic acid moiety: application to [14C]-labeled DP1 antagonistsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 1 2007Carl Berthelette Abstract Efficient carbon-14 labeling of four potent and selective DP1 antagonists is reported. The synthetic sequence began with ,-hydroxylation, reduction of an ester, followed by oxidative diol cleavage and aldehyde reduction. The resulting alcohol 4 was converted to a mesylate then nucleophilic substitution with [14C]-sodium cyanide was performed to yield a nitrile, which upon basic hydrolysis provided the carbon-14 labeled acid 1. Compound 2 was obtained from the same alcohol intermediate 4 and two diastereomeric compounds 6 and 7 were easily prepared from compound 2. Carbon-14 synthesis of compounds 1, 2, 6 and 7 were achieved in good yields, high radiochemical purity (>99%) and with high specific activity (45 mCi/mmol). Copyright © 2006 John Wiley & Sons, Ltd. [source] Semi-empirical studies of substituent effects on the ionization of bicyclooctane carboxylic acids and quinuclidinesJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 2 2003Helena Diez y Riega Abstract Semiempirical AM1 calculations were performed for a representative series of 4-substituted bicyclooctane carboxylic acids and quinuclidines. It was found that the Hammett constant, ,I, and the Swain and Lupton field constant, F, correlate linearly with the differences in the heat of formation of isodesmic reactions. These constants also correlate with the charges on the acid moiety of the bicyclooctane acids and their anions, and with the hydrogen net charge on the protonated quinuclidines. For all cases, the NO2 was the poorest correlated substituent. Copyright © 2003 John Wiley & Sons, Ltd. [source] Synthesis and characterization of the PEG-based nonionic surfactants endowed with carboxylic acid moiety at the hydrophobic terminalJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 24 2008Hiroshi Morikawa As a new class of stimulus-responsive surfactants, a series of ,-methyl-,-alkyl PEGs endowed with a carboxylic acid moiety at the hydrophobic terminal was successfully synthesized with 56,97% yields. They were characterized by IR, NMR spectroscopic and MALDI-TOF MS analyses. It is suggested by DLS measurement that the collapse of the micelle-like aggregation occurred under basic condition. This synthetic procedure would be applicable to surfactants with sufficient hydrophilic and lipophilic balances, allowing precise control of pH-responsive micellar systems. [source] Synthesis of Poly(ester-anhydrides) Based on Different Polyester PrecursorsMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 7 2004Harri Korhonen Abstract Summary: Poly(ester-anhydrides) were synthesised from poly(L -lactide), poly(D,L -lactide), and poly(, -caprolactone) prepolymers prepared by ring-opening polymerisation of cyclic esters in the presence of 1,4-butanediol or ricinoleic acid as co-initiator. The hydroxyl group end functionality of the prepolymers was converted to carboxylic acid functionality by reaction with succinic anhydride, and the polyester precursors were coupled by melt polycondensation to give poly(ester-anhydrides). 1,4-Butanediol was used as co-initiator to study the properties of poly(ester-anhydrides) prepared from different monomers, whereas ricinoleic acid was used as co-initiator to introduce a hydrophobic fatty acid moiety to the polyester precursor. In hydrolysis tests, the poly(ester-anhydrides) showed a two-stage degradation comprising a rapid hydrolysis of anhydride linkages within three days, followed by the slower hydrolysis of the remaining polyester oligomer. Weight loss of the poly(ester-anhydrides) depended most importantly on molecular weight and thermal properties of the polyester precursors; thus, poly(ester-anhydrides) prepared from low molecular weight prepolymers having thermal transitions below 37,°C showed very fast weight loss. [source] Brush-Like Amphoteric Poly[isobutylene- alt -(maleic acid)- graft -oligoethyleneamine)]/DNA Complexes for Efficient Gene TransfectionMACROMOLECULAR RAPID COMMUNICATIONS, Issue 13 2010Majad Khan Abstract Synthetic gene delivery vectors, especially cationic polymers have attracted enormous attention in recent decades because of their ease of manufacture, targettability, and scaling up. However, certain issues such as high cytotoxicity and low transfection efficiency problems have hampered the advance of nonviral gene delivery. In this study, we designed and synthesized brush-like amphoteric poly[isobutylene- alt -(maleic acid)- graft -oligoethyleneamine] capable of mediating highly efficient gene transfection. The polymers are composed of multiple pendant oligoethyleneimine molecules with alternating carboxylic acid moiety grafted onto poly[isobutylene- alt -(maleic anhydride)]. The polymer formed from pentaethylenehexamine {i.e., poly[isobutylene- alt -(maleic acid)- graft -pentaethylenehexamine)]} was able to condense DNA efficiently into nanoparticles of size around 200,nm with positive zeta potential of about 28,30,mV despite its amphoteric nature. Luciferase expression level and percentage of GFP expressing cells induced by this polymer was higher than those mediated with polyethyleneimine (branched, 25,kDa) by at least one order of magnitude at their optimal N/P ratios on HEK293, HepG2, and 4T1 cells. In vitro cytotoxicity testing revealed that the polymer/DNA complexes were less cytotoxic than those of PEI, and the viability of the cells after being incubated with the polymer/DNA complexes at the optimal N/P ratios was higher than 85%. This polymer can be a promising gene delivery carrier for gene therapy. [source] Effect of UVA or UVB Irradiation on Cutaneous Lipids in Films or in SolutionPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2010Chloé Merle The barrier function of the skin is largely due to the stratum corneum which is essentially composed of lipids. Different external factors, such as UV irradiation, affect this skin layer and are responsible for a destabilization of the supramolecular organization of its constituted lipids. In this work, mass spectrometry and infrared spectroscopy are combined to study the correlation between the formation of oxidative compounds by UV irradiation and the lipid organization. Experiments were carried out on unsaturated lipids in film or solution form, exposed to UVA or UVB irradiation. UV exposure leads to the formation of oxygenated entities in the case of lipids with an unsaturated fatty acid moiety, resulting in a decrease in their packing which is greater when the lipids are in solution. The packing decrease is even greater following UVB irradiation. [source] Identification of heat-induced degradation products from purified betanin, phyllocactin and hylocerenin by high-performance liquid chromatography/electrospray ionization mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2005Kirsten M. Herbach Betanin, phyllocactin (malonylbetanin) and hylocerenin (3-hydroxy-3-methylglutarylbetanin) were isolated from purple pitaya (Hylocereus polyrhizus [Weber] Britton & Rose) juice, and their degradation products generated by heating at 85°C were subsequently monitored by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. Thermal degradation of phyllocactin and hylocerenin in purified solution excluding the alleged protective effects by the juice matrix is reported for the first time. Betanin was predominantly degraded by hydrolytic cleavage, while decarboxylation and dehydrogenation were of minor relevance. In contrast, hylocerenin showed a strong tendency to decarboxylation and dehydrogenation, hydrolytic cleavage of the aldimine bond occurring secondarily. Phyllocactin degradation was most complex because of additional decarboxylation of the malonic acid moiety as well as generation and subsequent degradation of betanin due to phyllocactin demalonylation. Upon prolonged heating, all betacyanins under observation formed degradation products characterized by an additional double bond at C2C3. Hydrolytic cleavage of the aldimine bond of phyllocactin and hylocerenin yielded previously unknown acylated cyclo -dopa derivatives traceable by positive ionization, while application of ESI(,) facilitated the detection of a glycosylated aminopropanal derivative and dopamine, which have never been described before as betanin degradation products. Copyright © 2005 John Wiley & Sons, Ltd. [source] Collision-induced dissociation of glycero phospholipids using electrospray ion-trap mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2001Åsmund Larsen Characterisation of phospholipids was achieved using collision-induced dissociation (CID) with an ion-trap mass spectrometer. The product ions were compared with those obtained with a triple quadrupole mass spectrometer. In the negative ion mode the product ions were mainly sn -1 and sn -2 lyso-phospholipids with neutral loss of ketene in combination with neutral loss of the polar head group. Less abundant product ions were sn -1 and sn -2 carboxylate anions. CID using a triple quadrupole mass spectrometer, however, gave primarily the sn -1 and sn -2 carboxylate anions together with lyso-phosphatidic acid with neutral loss of water. For the ion trap a charge-remote-type mechanism is proposed for formation of the lyso-phospholipid product ions by loss of ,-hydrogen on the fatty acid moiety, electron rearrangement and neutral loss of ketene. A second mechanism involves nucleophilic attack of the phosphate oxygen on the sn -1 and sn -2 glycerol backbone to form carboxylate anions with neutral loss of cyclo lyso-phospholipids. CID (MS3 and MS4) of the lyso-phospholipids using the ion-trap gave the same carboxylate anions as those obtained with a triple quadrupole instrument where multiple collisions in the collision cell are expected to occur. The data demonstrate that phospholipid species determination can be performed by using LC/MSn with an ion-trap mass spectrometer with detection of the lyso-phospholipid anions. The ion-trap showed no loss in sensitivity in full scan MSn compared to multiple reaction monitoring data acquisition. In combination with on-line liquid chromatography this feature makes the ion-trap useful in the scanning modes for rapid screening of low concentrations of phospholipid species in biological samples as recently described (Uran S, Larsen,Å, Jacobsen PB, Skotland T. J. Chromatogr. B 2001; 758: 265). Copyright © 2001 John Wiley & Sons, Ltd. [source] Synthesis and Cytotoxic Activity of Novel Amidine Analogues of Bis(2-chloroethyl)amineARCHIV DER PHARMAZIE, Issue 8 2009Krzysztof Bielawski Abstract Novel nitrogen mustard agents 7,12 involving 4-(N,N -bis(2-chloroethyl)aminophenyl)propylamine linked to a 5-(4- N -alkylamidinophenyl)-2-furancarboxylic acid moiety by the formation of an amide bond have been synthesized, characterized, and evaluated for their in-vitro cytotoxic activity against MDA-MB-231 and MCF-7 human breast cancer cells. Evaluation of the cytotoxicity of 7,12 employing a MTT assay and inhibition of [3H]thymidine incorporation into DNA demonstrated that these compounds exhibit remarkable cytotoxic effects in comparison with 4-[bis(2-chloroethyl)amino]benzenebutanoic acid. Compounds 7 and 9, which possess a cationic amidine and 4,5-dihydro-1H -imidazol function moiety are approximately ten times more potent than 4-[bis(2-chloroethyl)amino]benzenebutanoic acid. The new compounds were evaluated as DNA topoisomerase II inhibitors. The cytotoxicity of the compounds 7,12 correlates with their DNA-binding affinities and their relative potency as topoisomerase II inhibitors. [source] The crystallographic structure of the aldose reductase,IDD552 complex shows direct proton donation from tyrosine 48ACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2004Federico Ruiz The X-ray crystal structure of human aldose reductase (ALR2) in complex with the inhibitor IDD552 was determined using crystals obtained from two crystallization conditions with different pH values (pH 5 and 8). In both structures the charged carboxylic head of the inhibitor binds to the active site, making hydrogen-bond interactions with His110 and Tyr48 and electrostatic interactions with NADP+. There is an important difference between the two structures: the observation of a double conformation of the carboxylic acid moiety of the inhibitor at pH 8, with one water molecule interacting with the main configuration. This is the first time that a water molecule has been observed deep inside the ALR2 active site. Furthermore, in the configuration with the lower occupancy factor the difference electron-density map shows a clear peak (2.5,) for the H atom in the hydrogen bond between the inhibitor's carboxylic acid and the Tyr48 side-chain O atom. The position of this peak implies that this H atom is shared between both O atoms, indicating possible direct proton transfer from this residue to the inhibitor. This fact agrees with the model of the catalytic mechanism, in which the proton is donated by the Tyr48 hydroxyl to the substrate. These observations are useful both in drug design and in understanding the ALR2 mechanism. [source] Fragmentation study of iridoid glycosides and phenylpropanoid glycosides in Radix Scrophulariae by rapid resolution liquid chromatography with diode-array detection and electrospray ionization time-of-flight mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 8 2010Qian Wu Abstract Rapid resolution liquid chromatography (RRLC) coupled with diode array detection (DAD) and electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS) method was applied to the mass spectral study of a series of naturally occurring iridoid glycosides and phenylpropanoid glycosides in Radix Scrophulariae, which provides higher speed and increased sensitivity without loss of resolution. With dynamic adjustment as the key role of the fragmentor voltage and confirmed with authentic standards, valuable structural information regarding the nature of both the glycoside skeletons was thus obtained. Most compositions were found to possess organic acid moiety such as cinnamoyl, caffeoyl and ferulyol. Besides extensive fragmentation of the carbohydrate moiety, losses of the hydroxyl and glucose residue units showed in the spectra, permitting the exploration of the skeleton and the identity of substituents in the molecule. Ten major iridoid glycosides and 10 phenylpropanoid glycosides were identified or tentatively characterized based on their retention times, UV and TOF MS data. The major fragmentation pathways of PGs in Radix Scrophulariae obtained through the MS data was schemed systematically for the first time, which provides a reference for other PGs derivatives. Copyright © 2009 John Wiley & Sons, Ltd. [source] Indispensable structure of solution additives to prevent inactivation of lysozyme for heating and refoldingBIOTECHNOLOGY PROGRESS, Issue 5 2009Tsuneyoshi Matsuoka Abstract This article investigates solution additives that prevent misfolding of lysozyme from heating treatment and during refolding processes. Comparison of heat treatment of native lysozyme and oxidative refolding from the reduced and denatured state of lysozyme in the presence of 44 different additives revealed an indispensable chemical structure for the additives to be effective against heat-induced misfolding and for refolding. The additives effective against heat treatment of native lysozyme possessed a main chain of the amino acid moiety. Amino acids that have esterificated and amidated carboxy groups prevented heat-induced misfoldings more effectively than amino acids themselves. On the other hand, the additives effective against oxidative refolding possessed a guanidium or ureido group. The former additives prevented hydrophobic interaction between the main chains of the unfolded polypeptide, while the latter additives increased the solubility of the aromatic and aliphatic side-chains. These data also support the fact that arginine (Arg) and Arg derivatives are versatile additives for both misfolding processes. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] 3,- Enolpyruvyl-UMP, a Novel and Unexpected Metabolite in Nikkomycin BiosynthesisCHEMBIOCHEM, Issue 11 2005Cristian Ginj Dipl.-Chem. An unexpected turn. NikO, the putative enolpyruvyl transferase involved in the formation of the aminohexuronic acid moiety of nikkomycins catalyzes the formation of 3,- enolpyruvyl-UMP from UMP (see scheme). This finding contradicts the current model for the biosynthesis of aminohexuronic acid. [source] | |||||||||||||||||||||||||||||||