Linear oligopeptides, 78. The effect of the insertion of the proline residue on the solution conformation of host peptides

Abstract

Abstract The conformational properties of three series of monodispersed, chemically and optically pure, PEG The following abbreviations have been used in the text: PEG, poly(ethylene glycol); ‐NHPEG, “amino‐PEG”; ‐NHPEG‐M, “amino‐PEG” ‐monomethyl ether; t ‐Boc, tert ‐butyloxycarbonyl; Z, benzyloxycarbonyl; Ala, alanine; Met, methionine; Gly, glycine; Glu, glutamic acid; Pro, proline; OBzl, benzyloxy; OEt, ethoxy; CD, circular dichroism; MeOH, methanol; TFE, 2,2,2‐trifluoroethanol; HFIP, 1,1,1,3,3,3‐hexafluoro‐2‐propanol. ‐bound linear host oligopeptides of the general formula \documentclass{article}\pagestyle{empty}\begin{document}$ t{\rm - Boc\rlap{--} (L - Met\rlap{--} )}_n {\rm NHPEG} $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ t{\rm - Boc\rlap{--} (L - X\rlap{--} )}_n {\rm NHPEG - M} $\end{document} [X = Ala, Glu(OBzl)] containing a single guest L ‐Pro residue at different positions in the main chain have been investigated in aqueous and alcoholic solutions as a function of concentration, temperature, and added salts using CD. The corresponding N‐deblocked peptides have also been examined. The incorporation of the L ‐Pro residue into a host petide chain blocks the extension of the α‐helical conformation at the level of the segment containing the guest residue at its N‐terminal end. The investigations reveal asymmetric helixnucleation properties of the L ‐Pro residue as predicted by theory. In β‐structure‐forming oligopeptides, the insertion of a L ‐Pro residue results in a significant destabilization of the ordered conformation. Thus, aggregation of peptide chains is less pronounced in these co‐oligopeptides.