NMR study of the peptide present in the principal neutralizing determinant (PND) of HIV-1 envelope glycoprotein gp120

Abstract

The peptide sequence Gly–Pro–Gly–Arg–Ala–Phe (GPGRAF) is present in many principal neutralizing determinants (PND) of the human immunodeficiency virus type-1 (HIV-1). It has been shown that peptides from the PND sequence contain a significant β turn in the conserved Gly–Pro–Gly–Arg sequence. In order to find out whether or not the smaller subunits also contain this turn, we have studied the NMR of a hexapeptide [GPGPRAF, peptide (I)], a heptapeptide Gly–Pro–Gly–Arg–Ala–Phe–Cys [GPGRAFC, peptide (II)] and a dodecapeptide [GPGRAFGPGRAF, peptide (III)], retaining the side chain protecting groups. Although the majority of conformations for these peptides are disordered, there is a considerable propensity of structures with β turn in the GPGR sequence. While peptide (I) and peptide (III) seem to have both type I and type II β turn conformations, peptide (II) shows a propensity of only type II β turn. The nascent structures obtained in these peptides may get stabilized as the receptor binding conformation in the presence of the receptors, thus playing a significant role in vaccine development against HIV.