G-Glycopeptides

Classes of antibiotics L P-lactam, T tetracycline, M macrolide, S sulphonamide, Ap amphenicol, A aminoglycosides, G glycopeptides, Q quinolone... 

Nowadays, antibiotics are primarily classified according to the mechanism of their action, with similarity of chemical structure as a secondary factor. Penicillin and its derivatives inhibit the formation of bacterial cell walls (Fig. 3.38). Cephalosporins have the same active mechanism. Other compounds are taken up into bacterial DNA to form unstable molecules (quinolones, metronidazole) or inhibit peptide synthesis (tetracychnes, aminoglycosides, macrolides). Some antibiotics (e.g. glycopeptides) exert a complex effect. 

Cassini G. Glycopeptides Antibiotic discovery and mechanism of action. Bushell ME, Grafe U, eds. Bioactive Metabolites from Microorganisms, VoL 27. Amsterdam Elsevier, 1980 221-235. 

Huang J, Habraken G, Audouin F, Heise A (2010) Hydrolytically stable bioactive synthetic glycopeptide homo- and copolymers by combination of NCA polymerization and click reaction. Macromolecules 43 6050-6057... 

Rohrer, J. S., Cooper, G. A., and Townsend, R. R., Identification, quantification, and characterization of glycopeptides in reversed-phase HPLC separations of glycoprotein proteolytic digests, Anal. Biodiem., 212, 7, 1993. 

The N-linked pentasaccharide core Man3(GlcNAc)2 glycopeptide bearing the extracellular MMP inducer sequence 517 (emmprin 34—58) has been successfully linked to G(l) PAMAM aminodendrimer by thioester activation (Fig. 63). The resulting octameric 30 kDa construct was obtained in low yield, but was purified by preparative electrophoresis and fully characterized by MALDI-TOF mass spectrometry. The multivalent architecture was built to evaluate the requirement of emmprin multimerization for inducing MMP expression.384... 

Harding, C.V., Kihlberg, J., Elofsson, M., Magnusson, G., and Unanue, E.R. (1993) Glycopeptides bind MHC molecules and elicit specific T cell responses. J. Immunol. 151, 2419-2425. 

Dalbavancin Glycopeptide 2007 2008 2009 SSSIs caused by G+ bacteria including MRSA... 

Carboxylic acid-terminated organosilanes were used in the early studies on chemically bonded glycopeptides to immobilize vancomycin and thiostrepton via then-amino groups, leading to the formation of stable amide bonds between antibiotics and modified silica [7]. In a typical reaction, 4 g of dry silica gel is slurried on 50 mL of dry toluene. Two grams of [l-(carbomethoxy)ethyl]methyldichlorosilane or [2-(carbomethoxy)ethyl]trichlorosilane is dissolved in 15 mL of dry toluene contained in a dropping flask. The organosilane solution is added dropwise over 30 min... 

NaCNBH3 (10 mM) in phosphate buffer (pH = 3). The slurry is sonicated for 1 h, centrifuged, and the cyanoborohydride solution eliminated. The modified silica is washed with water and methanol, and then dried. This chemistry of binding provided for vancomycin a substantial bonding density of 120 p,mol/g (0.40 p,mol/m ) [70] (see Table 2.2). Surface coverage data for ristocetin A [75] and glycopeptide MDL 63,246 [43,44] were not provided by the authors. 

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