Conformational analysis of peptide T and of its C‐pentapeptide fragment

Abstract

The synthetic peptide of sequence H‐Ala‐Ser‐Thr‐Thr‐Thr‐Asn‐Tyr‐Thr‐OH, termed peptide T, a competitor of the Human Immunodeficiency Virus in the binding to human T cells, and its C‐terminal pentapeptide fragment, were studied by ¹H‐nmr in DMSO solution to determine conformational preferences. The observation of nuclear Overhauser enhancements (NOEs) for both peptides, and unusual finding for small linear peptides, allowed complete sequence‐specific resonance assignments. Long‐range NOEs, ring‐current shifts, and the very small temperature coefficient of the Thr⁸ NH chemical shift suggest, for the zwitterionic form of peptide T, the presence in solution of a β‐turn involving Thr⁵, Asn⁶, Tyr⁷ and Thr⁸. This conformational feature is consistent with previous structure–activity relationship studies indicating the invariance of the same residues in several potent pentapeptide analogues. The studied pentapeptide fragment, although less structured, shows some tendency to fold even in a polar solvent such as DMSO. Preliminary chemotaxis data on some pentapeptide analogues are consistent with our structural model.