Amphiphilic α-helical structure in water stabilized by dioctadecyl chain

Abstract

The peptides H-(Leu-Aib-Lys-Aib-Aib-Lys-Aib)₃-X [X = OMe, P21OMe; X =-Ala-N(C₁₈H₃₇)₂, P21D], have been synthesized as models for biologically active peptides having long alkyl chains, and the effect of the alkyl chain on the peptide conformation has been studied. CD measurements revealed that the α-helix content of P21D in water was higher than in P21OMe, while their conformations were nearly the same in methanol. Guanidine hydrochloride (GdnHCl), which is a denaturant of proteins, increased the helix content of P21D, but decreased the helix content of P21OMe. The stabilization of the helical structure of P21D at high concentrations of GdnHCl is ascribed to a reduction in the electrostatic repulsion between the ammonium groups of P21D at high ionic strength. It is notable that in water the major fraction of P21D exists as a monomer, but the number of P21D molecules involved in higher aggregates is significant, as revealed by dynamic light scattering measurement. A short-chain peptide, H-Leu-Aib-Lys-Aib-Aib-Lys-Aib-AlaN(C₁₈H₃₇)₂, formed much larger aggregates in water than P21D. It probably formed micelles without taking on a helical conformation. Therefore, the connection of two long alkyl chains at the C terminal of a longchain amphiphilic helical peptide is a suitable method for stabilizing the helix conformation without being accompanied by severe aggregation.