CHEMICAL GLYCOSYLATION OF PEPTIDE T AT NATURAL AND ARTIFICIAL GLYCOSYLATION SITES STABILIZES OR REARRANGES THE DOMINANT REVERSE TURN STRUCTURE

Peptide T (H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH), a fragment of HIV gp120, has been reported to inhibit binding of the virus to the CD4 receptor. The peptide assumes a β-turn secondary structure, and stabilization of the conformation may increase the biological activity. We synthesized the octapeptide and its C-terminal pentapeptide fragment, unmodified and glycosylated, when monosaccharides were walked through the molecules. Incorporation of the sugar into the longer peptide resulted in the stabilization of the type I (III) β-turn, as indicated by circular dichroism measurements. While N-terminal glycosylation of the shorter peptide also stabilized the type I (III) β-turn, the circular dichroism spectra revealed slightly different type II β-turn structures when the carbohydrate moiety was incorporated into mid-chain or C-terminal positions. Modification of biologically active reverse-turn structures by glycosylation offers a viable alternative to the peptide mimetics approach in drug design. © 1992.