Peptide T revisited: Conformational mimicry of epitopes of anti-HIV proteins

Peptide T (ASTITNYT), a fragment corresponding to residues 185- 192 of gp12 0, the coat protein of HIV, is endowed with several biological properties I n vitro, notably inhibition of the binding of both isolated gp120 and HI-1 to the CD4 receptor, and chemotactic activity. Based on previous nuclear ma gnetic resonance (NMR) studies performed in our laboratory, which were cons istent with a regular conformation of the C-terminal pentapeptide, and SAR studies showing that the C-terminal pentapeptide retains most of the biolog ical properties, we designed eight hexapeptides containing in the central p art either the TNYT or the TTNY sequence, and charged residues (D/E/R) at t he two ends. Conformational analysis based on NMR and torsion angle dynamic s showed that all peptides assume folded conformations, albeit with differe nt geometries and stabilities. In particular, peptides carrying an acidic r esidue at the N-terminus and a basic residue at the C-terminus are characte rized by stable helical structures and retain full chemotactic activity. Th e solution conformation of peptide ETNYTR displays strong structural simila rity to the region 19-26 of both bovine pancreatic and bovine seminal ribon uclease, which are endowed with anti-HIV activity. Moreover, the frequent o ccurrence, in many viral proteins, of TNYT and TTNY, the two core sequences employed in the design of the hexapeptides studied in the present work, hi nts that the sequence of the C-terminal pentapeptide TTNYT is probably repr esentative of a widespread viral recognition motif. Copyright (C) 2001 Euro pean Peptide Society and John Wiley Br Sons, Ltd.