Terminal effect of chiral residue on helical screw sense in achiral peptides

Abstract

To understand the terminal effect of chiral residue for determining a helical screw sense, we adopted five kinds of peptides I–V containing N- and/or C-terminal chiral Leu residue(s): Boc–L-Leu–(Aib–ΔPhe)2–Aib–OMe (I), Boc–(Aib–ΔPhe)2–L-Leu–OMe (II), Boc–L-Leu–(Aib–ΔPhe)2–L-Leu–OMe (III), Boc–D-Leu–(Aib–ΔPhe)2–L-Leu–OMe (IV), and Boc–D-Leu–(Aib–ΔPhe)2–Aib–OMe (V). The segment –(Aib–ΔPhe)2– was used for a backbone composed of two “enantiomeric” (left-/right-handed) helices. Actually, this could be confirmed by 1H-nmr [nuclear Overhauser effect (NOE) and solvent accessibility of NH resonances] and CD spectroscopy on Boc–(Aib–ΔPhe)2–Aib–OMe, which took a left-/right-handed 310-helix. Peptides I–V were also found to take 310-type helical conformations in CDCl3, from difference NOE measurement and solvent accessibility of NH resonances. Chloroform, acetonitrile, methanol, and tetrahydrofuran were used for CD measurement. The CD spectra of peptides I–III in all solvents showed marked exciton couplets with a positive peak at longer wavelengths, indicating that their main chains prefer a left-handed screw sense over a right-handed one. Peptide V in all solvents showed exciton couplets with a negative peak at longer wavelengths, indicating it prefers a right-handed screw sense. Peptide IV in chloroform showed a nonsplit type CD pattern having only a small negative signal around 280 nm, meaning that left- and right-handed helices should exist with almost the same content. In the other solvents, peptide IV showed exciton couplets with a negative peak at longer wavelengths, corresponding to a right-handed screw sense. From conformational energy calculation and the above 1H-nmr studies, an N- or C-terminal L-Leu residue in the lowest energy left-handed 310-helical conformation was found to take an irregular conformation that deviates from a left-handed helix. The positional effect of the L-residue on helical screw sense was discussed based on CD data of peptides I–V and of Boc–(L-Leu–ΔPhe)n–L-Leu–OMe (n = 2 and 3). © 1999 John Wiley & Sons, Inc. Biopoly 49: 551–564, 1999