Screw sense preference of non-polar L-amino acid residues second from the N-terminal position

Abstract

To understand the positional effects of a single chiral residue on the helical screw sense of an achiral segment, we adopted five kinds of peptides Boc-Aib-X*-(Aib-Δ^ZPhe)₂-Aib-OMe (Boc, t-butoxycarbonyl; Aib, α-aminoisobutyric acid; Δ^ZPhe, (Z)-dehydrophenylalanine; OMe, methoxy), wherein the X* residue is an L-residue of leucine (Leu), alanine (Ala), valine (Val), phenylalanine (Phe), or 1-naphthylalanine (Nap). Here the segment -(Aib-Δ^ZPhe)₂-Aib-OMe was employed as an achiral backbone for generating two “enantiomeric” (left-handed/right-handed) helices. All of the peptides are folded into a 3₁₀-type helical conformation in chloroform, as evidenced by FT-IR and ¹H NMR techniques. A CD analysis of these peptides indicates that they adopt both left-handed and right-handed helices, and that the prevailing screw sense as well as the screw sense bias depend on the type of solvent. Thus, the L-residue located at the position second from the N-terminus plays a unique role for energetically permitting both helices. These peptides also undergo a solvent-induced interconversion between both helices. The rank order of the penultimate L-residues for inducing a right-handed screw sense is Val > Leu ∼ Ala > Phe > Nap, of which the reverse order represents the tendency to promote a left-handed screw sense. The prevailing screw sense induced by the penultimate L-residue is also discussed on the basis of conformational energy calculations. In conclusion, we here have been able to express experimentally a unique screw sense preference of these non-polar L-amino acids.