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

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 m M by 1 H‐nmr spectroscopy. Both peptides associate in CDCl 3 at concentrations ≥ 2 m M , while there is no evidence for aggregation in (CD 3 ) 2 SO. 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 1 H‐, 13 C‐nmr, and ir studies of analog 2 . The influence of backbone conformation on the ease of peptide aggregation is demonstrated by ir studies in CHCl 3 and CD studies in dioxane.