Glycopeptide Derivatives Research Articles

Synthesis of Normuramic Acid Carba Analog and Its Glycopeptide Derivative Resistant to β-Elimination Splitting of the Side Chain

Carba analogs of normuramic acid, i.e., 3-(benzyl 2-acetamido-2,3-dideoxy-4,6-O-isopropylidene-α-D-glucopyranosid-3-yl)propanoic acid derivatives (nitrile or esters) 3a-3c were prepared by addition of radicals generated from benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-3-O-[(methylsulfanyl)thiocarbonyl]- (2a) or -3-O-(phenoxythiocarbonyl)-α-D-glucopyranoside (2b) with Bu3SnH to acrylonitrile or acryl esters. Alkaline hydrolysis of ethyl ester 3c afforded 3-(benzyl 2-acetamido-2,3-dideoxy-4,6-O-isopropylidene-α-D-glucopyranosid-3-yl)propanoic acid (5). Coupling of acid 5 with L-2-aminobutanoyl-D-isoglutamine benzyl ester trifluoroacetate and subsequent deprotection of the intermediate 6 furnished N-[3-(2-acetamido-2,3-dideoxy-α-D-glucopyranosid-3-yl)propanoyl]-L-2-aminobutanoyl-D-isoglutamine (7).

ChemInform Abstract: Glycopeptide Resistance in Multiple Antibiotic‐Resistant Gram‐Positive Bacteria: A Current Challenge for Novel Semi‐Synthetic Glycopeptide Derivatives

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Section Review Anti-infectives: New approaches to the treatment of vancomycin-resistant bacterial infections

Commercially available glycopeptides Vancomycin (V) and Teicoplanin (T) are drugs of choice for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (CNS), which are resistant to beta-lactams and almost all other first-line antibiotics. They are extensively used in the treatment of severe infections caused by multi-resistant Gram-positive pathogens including enterococci. Enterococcal infections have become a dramatic clinical problem since few antibacterial agents are efficacious against these refractory organisms and increasing resistance is rapidly eliminating the current options. The recent emergence and spread of resistance also to glycopeptides in VanA enterococci poses a serious threat for the future. Some strains of methicillin-resistant CNS have reduced susceptibility to T and occasionally to V. Currently, a major concern is the possibility already demonstrated at laboratory level, that high glycopeptide resistance could be transferred from enterococci to staphylococci. It follows that there is an urgent need for new more potent glycopeptides which combine improved activity against methicillin-resistant staphylococci with excellent activity against highly glycopeptide-resistant enterococci (GRE), or alternative drugs effective against these multi-resistant bacteria. This article describes the most recent findings and results achieved in this field with new glycopeptide derivatives and novel approaches based on modifications of the natural glycopeptide-core structure. Other promising investigational drugs potentially useful for overcoming the serious therapeutic problem of glycopeptide-resistant bacterial infections are also reviewed.

Synthesis of glycopeptide derivatives of Peptide T on a solid phase using an allylic linkage

Glycopeptides are receiving more and more interest as model compounds for biological and medicinal research. Here we report on a methodology for the synthesis of these complex molecules on a solid phase. Using allylic anchoring groups we are able to construct, detach and isolate the glycopeptides in high yield without affecting any temporary protecting group or moiety of the conjugate. The strategy and the experimental data of two syntheses of glycosylated Peptide T, a partial sequence of gp 120 of HIV-1, are described in detail.

Topography of binding sites of animal lectins: ligands’ view

Abstract

Synthesis of a branched glycopeptide derivative containing terminal d-mannose 6-phosphate residues

A branched glycopeptide derivative incorporating two d-mannose 6-phosphate residues was prepared by coupling 6-aminohexyl 6- O-[bis(2,2,2-trichloroethoxy)phosphinyl]-α- d-mannopyranoside with N-acetyl- l-tyrosyl- l-aspart-oyldi- l-alanine followed by reductive deprotection of the phosphate group.

Synthesis of glycopeptide derivatives of glycyrrhizinic acid and their immunomodulatory properties

Synthesis of glycopeptide derivatives of glycyrrhizinic acid and their immunomodulatory properties

Identification of fluorescent glycopeptide derivatives by two consecutive high pressure liquid chromatographic procedures.

Reversed phase high pressure liquid chromatography (HPLC) was used to separate individual components of the complex glycopeptide antibiotic teicoplanin in microgram quantities with gradient elution. Each of eight different fractions was then subjected to a specific and highly sensitive HPLC method, which has been developed for the determination of teicoplanin concentrations in biological specimens. This analytical procedure includes precolumn derivatization with fluorescamine and isocratic elution. The fluorescent teicoplanin derivatives were identified by comparing their retention times in both HPLC procedures. Derivatization resulted in increased hydrophobicity and improved chromatographic separation, but the order of elution of the different compounds was not changed. The antimicrobial activity of the individual underivatized fractions correlated with their respective contents of total teicoplanin A2, whereas the pseudo-aglycone A3 appeared less active. Similar techniques have the potential to be applied to other complex glycopeptide antibiotics.

Comparative study of the carbohydrate chain of ovalbumin from various avian species by high pressure liquid chromatography

1. 1. 5-dimethylaminonaphthalene-1-sulfonyl derivatives of asparaginyl glycopeptides (DNS-GPs) from avian ovalbumins were analysed by C-18 reverse-phase high pressure liquid chromatography (HPLC). 2. 2. DNS-GPs from seven chicken subspecies were separated into 13 common peaks, named C1, C2, . . . C3, and an additional peak, C0 in some preparations. 3. 3. Peaks C0 through C3 corresponded to a series of the DNS-GPs bearing (Man)8-5 (GlcNAc)2 respectively. 4. 4. DNS-GP from quail ovalbumin was separated into 2 major peaks (Qt and Q2) and one minor peak (Q3), DNS-GP from goose ovalbumin was separated into 14 peaks, G1 through G14, and DNS-GP from turkey ovalbumin was separated into two major peaks (T1 and T2). 5. 5. We found that all or some of the peaks from other avian species co-eluted with corresponding peaks, [Cx (x = 0 to 13)] derived from chicken ovalbumin. 6. 6. These were as follows: Q1, [C0]; Q2, [C1]; Q3, [C2]; T1, [C3]; T2, [C4]; G5, [C6]; G8, [C8]; G10, [C10]; G12, [C11]; G13, [C12]; G14, [C13].

Teratocarcinoma stem cells have a cell surface carbohydrate-binding component implicated in cell-cell adhesion

Teratocarcinoma stem cells maintained in the undifferentiated state express a carbohydrate-binding component that recognizes oligomannosyl residues. This cell surface molecule is detected by a rosette assay in which the stem cells form rosettes with glutaraldehyde-fixed trypsinized rabbit erythrocytes. Addition of simple sugars to the assay mixture has little effect, but rosette formation is inhibited by a series of mannose-rich glycoproteins (yeast invertase, yeast mannans and horseradish peroxidase). Periodate oxidation eliminates the inhibitory activity of invertase whereas pronase digestion has little effect, indicating that carbohydrate moieties are essential for inhibition. Invertase and its glycopeptide derivatives also inhibit the reaggregation of dispersed stem cells and promote the dissociation of preformed aggregates. These results suggest that intercellular adhesion of teratocarcinoma stem cells may be the consequence of the interaction of a lectin-like component detected in the rosette assay with a complementary oligosaccharide receptor on adjacent cells.

Synthesis of glycopeptide derivatives containing the 2-acetamido- N-( L-aspart-4-oyl)-2-deoxy-β- D-glucopyranosylamine linkage and having the amino acid sequences 32–34, 33–35,33–37, and 33–38 of bovine ribonuclease

The synthesis is described of the glycotripeptide derivatives 2-acetamido-3,4,6-tri- O-acetyl- N-[ N-(benzyloxycarbonyl)- L--seryl- L-nitroarginyl- L-aspart-4-oyl]-2-deoxy-β- D-glucopyranosylamine, 2-acetamido-3,4,6-tri- O-acetyl- N-[ N-(benzyloxycarbonyl)- L-seryl- L-nitroarginyl- L-aspart-1-oyl-(1- p-nitrobenzyl ester)-4-oyl]-2-deoxy-β- D-glucopyranosylamine, and 2-acetamido-3,4,6-tri- O-acetyl- N-[ N-(benzyloxycarbonyl)- L-nitroarginyl- L-aspart-1-oyl-( L-leucine methyl ester)-4-oyl]-2-deoxy-β- D-glucopyranosylamine, and of the glycopentapeptide and glycohexapeptide derivatives 2-acetamido-3,4,6-tri- O-acetyl- N-[ N-(benzyloxycarbonyl)- L-nitroarginyl- L-aspart-1-oyl-( L-leucyl- L-threonyl-threonyl- N ε-tosyl- L-lysine-( p-nitrobenzyl ester)-4-oyl]-2-deoxy-β- D-glycopyranosylamine and 2-acetamido-3,4,6-tri- O-acetyl- N-[ N-(benzyloxycarbonyl)- L-nitroarginyl- L-aspart-1-oyl-( L-leucyl- L-threonyl- N ε-tosyl- L-lysyl- L-aspartic 1,4-di- p-nitrobenzyl ester)-4-oyl]-2-deoxy-β- D-glucopyranosylamine.

Immunological investigations of penicillium—II. Primary binding of glycopeptides and glycopeptide derivatives to specific antibodies

Immunological investigations of penicillium—II. Primary binding of glycopeptides and glycopeptide derivatives to specific antibodies

Immunological investigations of penicillium—II. Primary binding of glycopeptides and glycopeptide derivatives to specific antibodies

An exocellular glycopeptide from Penicillium charlesii has been shown previously to contain a high mol. wt polysaccharide and several oligosaccharides attached to the peptide through seryl and threonyl residues. Guinea pigs immunized with the glycopeptide conjugated to bovine gamma globulin, produced nonprecipitating antibodies to the polysaccharide portion of the glycopeptide. However, a technique was developed for measuring the primary binding of the glycopeptide by the guinea pig antibodies. It was found that the antigen-antibody complex could be precipitated by 40% ammonium sulfate, whereas negligible quantities of the glycopeptide alone or glycopeptide incubated with normal guinea pig sera were precipitated under these conditions. Equations predicting the influence of the ratio of a weighted dissociation constant representing the various antigen-antibody complexes/antibody concentrations, β/[ Ab t] , on antigen binding and the influence of this ratio on inhibition of antigen binding by hapten were derived. The data obtained with the fungal glycopeptide as an antigen were interpreted in terms of this model. The experiments showed that antibodies in the guinea pig sera were directed toward the polysaccharide portion of the glycopeptide, and not toward the peptide portion or the oligosaccharides. Furthermore, a glycopeptide deficient in galactofuranosyl and phosphorus moieties from a uridine diphosphate galactose 4-epimerase negative mutant of P. charlesii competed with wild type glycopeptide for antibody. It appeared that mannopyranosyl residues associated with an, as yet unidentified, acid labile material were the major immunodeterminant groups of the glycopeptide which bound to guinea pig sera. In contrast to its behavior in guinea pig antisera, the polysaccharide portion of the glycopeptide did not compete with the glycopeptide for antibodies in rabbit antisera. In addition the peptide portion of the glycopeptide did not compete with the glycopeptide in the rabbit antisera. Further, dilute acid treatment of the glycopeptide did not destroy its ability to bind to rabbit antibodies. These data suggest that the oligosaccharides attached to the peptide serve as the antigenic determinats which bind to rabbit antibodies.

Some further studies on the synthesis of glycopeptide derivatives: 2-acetamido-2-deoxy-beta-D-glucopyranosylamine derivatives.

1. The isolation, characterization and properties of two by-products in the preparation of 2-acetamido-3,4,6-tri-O- acetyl-2-deoxy-beta-d-glucopyranosylamine are described. They are bis(2-acetamido-2-deoxy-d-glucopyranosyl)amines. 2. An independent synthesis of the bis-glycopyranosylamines is reported and conditions are given for their preparation in high yield. 3. Further improvements are given for the synthesis of 2-acetamido-1-N-(beta-l- aspartyl)-2-deoxy-beta-d-glucopyranosylamine and the alpha-l-aspartyl isomer. 4. The synthesis of 2-acetamido-1-N-acetyl-2-deoxy-beta-d-glucopyranosylamine is described.