Interactions of cyclic hexapeptide cyclo(Pro-Sar-Sar) 2 with small molecules

Abstract

N.m.r. and c.d. spectroscopy have been used to study the interactions of cyclic hexapeptide cyclo(Pro-Sar-Sar) 2 with metal ions and ammonium ions. Cyclo(Pro-Sar-Sar) 2 was found to form complexes with Li +, K −, Ba 2+ and Cu 2+, accompanying the conformational change into a single conformer, and the conformation of cyclo(Pro-Sar-Sar) 2 in the Li +-complex was different from that in the Cu 2+-complex. These findings indicate conformational flexibility of cyclo(Pro-Sar-Sar) 2. The equilibrium constant for the complexation with Li + was 2.3 × 10 2l mol −1, and cyclo(Pro-Sar-Sar) 2 adopted an asymmetric conformation in the complex. The addition of α-amino acid ester hydrochloride also caused the conformational change of cyclo(Pro-Sar-Sar) 2), but in this case it did not converge into a single conformation. This type of interaction was strengthened with aromatic α-amino acid ester hydrochloride due to the aromatic-amide interactions. Finally, the rates of exchange between unbound α-amino acid ester hydrochlorides and those complexed with cyclo(Pro-Sar-Sar) 2 were found to be different, according to the nature of α-amino acid.