SYNTHESIS OF AN N-LINKED GLYCOPEPTIDE FROM VITAMIN-K-DEPENDENT PROTEIN-S

A novel asparagine building block having an N-linked chitobiose moiety protected with acid-labile TBDMS groups has been prepared. The buildi ng block was used in Fmoc solid-phase synthesis of a glycopeptide frag ment corresponding to residues 447-460 of protein S which has a potent ial N-glycosylation site at Asn(458). The TBDMS groups of the chitobio se moiety were removed during cleavage of the glycopeptide from the so lid phase, thus simplifying synthesis as compared to when using acetyl protection for the carbohydrate, Protein S is an anticoagulant which may be inactivated by complexation by C4b binding protein (C4BP). The protein S 447-460 glycopeptide was found to be a more efficient inhibi tor of complex formation than the non-glycosylated parent peptide, ind icating that protein S may carry an N-linked glycan at Asn(458). (C) 1 998 Elsevier Science Ltd. AII rights reserved.