Chemical glycosylation of peptide T at natural and artificial glycosylation sites stabilizes or rearranges the dominant reverse turn structure

• Published in: Biochemical and biophysical research communications Vol. 184; no. 2; p. 1125
• Main Authors: Urge, L, Gorbics, L, Otvos, Jr, L
• Format: Journal Article
• Language: English
• Published: United States 30-04-1992
• Subjects: Amino Acid Sequence; Circular Dichroism; Glycopeptides - chemical synthesis; Glycopeptides - chemistry; Glycosylation; Molecular Sequence Data; Peptide T - chemical synthesis; Peptide T - chemistry; Protein Conformation; Spectrophotometry, Ultraviolet; Structure-Activity Relationship
• ISSN: 0006-291X
• DOI: 10.1016/0006-291X(92)90709-T

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 beta-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) beta-turn, as indicated by circular dichroism measurements. While N-terminal glycosylation of the shorter peptide also stabilized the type I (III) beta-turn, the circular dichroism spectra revealed slightly different type II beta-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.