ISOMERIZATION OF THE XAA-PRO PEPTIDE-BOND INDUCED BY IONIC INTERACTIONS OF ARGININE

Inclusion of Arg or Pro residues in proteins and peptides has been pro ved to play an essential role in biochemical functions through ionic i nteractions, conformational transitions, and formation of turns as wel l. In this study we present the conformational properties of the Ac-Ar g-Ala-Pro (1), Ac-Arg-Ala-Pro-NH2 (2), Ac-Arg-Pro-Asp-NH2 (3), and Ac- Arg-Pro-Asp (4) tripeptides peptides, using H-1-nmr spectroscopy and m olecular dynamics. These peptides were, modeled with the aim of studyi ng the role of the Arg-guanidinium to carboxylate ionic interactions o n the Xaa-Pro peptide bond isomerization. It was found with I and 4 th at arginine preferentially interacts with the C-terminal carboxylate g roup, even though the beta-carboxylate is also accessible. This tenden cy of the Arg moiety was found to induce the cis disposition of the Al a-Pro peptide bond in I, It was also confirmed that the Arg ... Asp si de chain-side chain ionic interactions in 3 plays a key role in backbo ne folding and structural stabilization through a type I beta-turn. Th e nmr pattern for 3 showed a remarkable similarity with that for vario us Arg-Tyr-Asp containing peptides, a sequence that is crucial for the adhesion properties of the Leishmania gp63 glycoprotein. (C) 1996 Joh n Wiley & Sons, Inc.