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 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.
Urge
L
L
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Gorbics
L
L
Otvos
L
L
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D006031:Glycosylation; D008969:Molecular Sequence Data; D015717:Peptide T / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D006020:Glycopeptides; D015717:Peptide T