Conformational effects on peptide aggregation in organic solvents: spectroscopic studies of two chemotactic tripeptide analogs

Abstract

The aggregation behavior of the chemotactic peptide analogs, Formyl-Met-Leu-Phe-OMe (1) and Formyl-Met-Aib-Phe-OMe (2), has been studied in chloroform and dimethylsulfoxide over the concentration range of 0.2-110 mM by ¹H-nmr spectroscopy. Both peptides associate in CDCl₃ at concentrations ≥ 2 mM, while there is no evidence for aggregation in (CD₃)₂SO. Analog 1 adopts an extended conformation in both solvents favoring association to form β-sheet structures. A folded, γ-turn conformation involving a 3 →1 hydrogen bond between Met CO and Phe NH is supported by ¹H-, ¹³C-nmr, and ir studies of analog 2. The influence of backbone conformation on the ease of peptide aggregation is demonstrated by ir studies in CHCl₃ and CD studies in dioxane.