A Study of Chain-Length Effect on Helical Screw Sense in Peptides Having an N-Terminal L-Leu Residue

Abstract

In order to clarify which helical screw sense is dominated depending on chain-length of peptides when an L-residue is introduced into the N-terminal position of achiral helical segments, we prepared three kinds of peptides I—III: Boc–L-Leu–(Aib-ΔPhe)n–Aib–OMe (n=2—4) I—III (Boc, t-butoxycarbonyl; Aib, α-aminoisobutyric acid; ΔPhe, Z-dehydrophenylalanine; OMe, methoxy). Here the segment –(Aib–ΔPhe)n–Aib–OMe was used for an achiral backbone composed of two “enantiomeric” (left-/right-handed) helices. Peptides I—III were found to form a 310-type helical conformation in chloroform, from the position of amide I band in FT-IR spectra and solvent accessibility of NH resonances in 1H NMR measurement. CD spectra of peptides I—III showed exciton couplets around 280 nm with a positive peak at longer wavelengths in chloroform, acetonitrile, methanol, and tetrahydrofuran. The sign of exciton couplets indicates that the main-chains prefer a left-handed screw sense. Consequently, an N-terminal L-Leu residue induces a left-handed screw sense preferentially, irrespective of chain lengths for achiral helical segments (5—9 residues).This result could be supported by conformational energy calculation on acetyl–L-Leu–(Aib–ΔPhe)4–Aib–OMe, in which a left-handed helical conformation was predominant. Also, in the lowest-energy left-handed helix, an N-terminal L-Leu residue takes an irregular conformation that deviates from a left-handed 310-/α-helical region in conformational space of (φ, ψ).