Joachim März

Synthesis of 2-acetamido-2-deoxyglucosylasparagine glyco-tripeptides and -pentapeptides by selective C- and N-terminal elongation of the peptide chain

The synthesis of protected 2-acetamido-2-deoxyglucosylasparagine glycopeptides, using the allyl ester as the C-terminal protecting group, their deprotection, and some possible applications of these glycopeptides for the synthesis of modified silica gels and the construction of liposomes are described. The selective carboxyl deblocking is achieved under neutral conditions by rhodium(I)-catalyzed isomerization of the allyl group followed by hydrolysis of the resulting propenyl ester. The tert-butoxycarbonyl group can be cleaved selectively in the presence of the allyl ester with hydrogen chloride in ether. The allyl ester and the acetates can be removed simultaneously with ammonia in methanol. This method opens up a preparative route to glycopeptide model structures of biological interest.

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

Abstract 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.

SYNTHETIC TUMOR-ASSOCIATED GLYCOPEPTIDE ANTIGENS

Glycopeptides with TN antigen (GalNAc)Ser/Thr and T-antigen structures (beta Gall-3GalNAc)Ser/Thr, described as tumor-associated antigens, were synthesized and coupled to bovine serum albumin. Alternatively, synthetic methods for the construction of beta-anomeric analogues of the TN and T-antigen glycopeptides were developed, aiming at antigenic structures having a varied stereochemistry of the linkage between the carbohydrate and the peptide moiety. As a further type of potential tumor-associated antigen, fucosyl-chitobiose asparagine glycopeptides were synthesized, deprotected, and coupled to bovine serum albumin. The chemical methods developed now make the complex sensitive glycoprotein partial structures accessible in analytically pure form and in preparative amounts.