C-glycopeptide

Fig. 1.—Mass Fragmentograms of Partially Methylated Alditol Acetates Obtained from Rat-brain Glycopeptides. [(A) Fraction A glycopeptides, (B) fraction B glycopep-tides, and (C) fraction C glycopeptides. Peak 1, 2,3,4-tri-O-methylfucitol peak 2,...

The replacement of the anomeric oxygen by a CF2 has been considered to obtain hydrolytically stable difluoro-C-glycosides, difluoro-C-disaccharides and difluoro-C-glycopeptides. These compounds have been synthesized [65-68], but their use as inhibitors does not seem to have been biologically validated. 

Naturally occurring C-glycopeptides have recently been discovered. A C-linked a-mannose, where the mannopyranosyl Cl atom is directly linked to the C2 atom in a Trp indole ring, has been identified in humans 435 38 and in nonhuman organisms)525 Stereo-controlled synthesis of a-C-mannosyltryptophan has been reported)439,440,526,527 ... 

Anomeric Glycosyl Dianions as Intermediates in the Synthesis of C-Glycopeptides... 

Synthesis of C-Glycopeptides by Radical Addition of Glycosyl Bromide to a... 

H. Kessler, V. Wittmann, M. Kock, and M. Kottenhahn, Synthesis of C-glycopeptides via radical addition of glycosyl bromides to dehydroalanine derivatives, Angew. Chem. Int. Ed. Engl. 3/ 902 (1992). 

Wang LX, Tang M, Suzuki T, Kitajima K, Inoue Y, Inoue S, Fan JQ, Lee YC. Combined chemical and enzymatic synthesis of a C-glycopeptide and its inhibitory activity toward glycoamidases. J. Am. Chem. Soc. 1997 119 11137-11146. 

The full capacity of the lipase-mediated technique for C-terminal deprotection is demonstrated in the synthesis of complex C>-glycopeptides, which are sensitive to both acids and bases, The key starting material, serine glycoside heptyl ester 11, is selectively depro-tected at the C-terminus by lipase obtained from the fungus Mucor javanicus (Scheme 22). The free carboxylic acid derivative 12 is coupled with an N-terminally protected glyco-dipeptide 13 to generate the tripeptide 14. 

The C-glycopeptide was assayed for inhibition against several glycoamidases of bacterial, plant, and animal origin. The assay results indicated that the C-glycopeptide was capable of inhibiting the entire range of enzymes tested. As such, mechanistic studies of further enzymatic activity are possible with constructs of a similar nature. 

Scheme 20 C-Glycopeptide mimic of a MUCl antigen linked to TTox.

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