Left-Handed Helical Preference in an Achiral Peptide Chain is Induced by an L-Amino Acid in an N-Terminal Type II β-Turn

摘要

Oligomers of the achiral quaternary α-amino acid Aib (2-aminoisobutyric acid) adopt helical conformations known as 3_(10) helices, in which each monomer is hydrogen-bonded to the monomer three positions further along the chain [1]. Without any stereochemical bias, these Aib homopeptides display no preference for left-(M) or right-handed (P) helicity and undergo fast conformational inversion (k ~ 10~(-3) s). Such dynamic equilibrium may be biased m tavour or either the right-or left-handed screw sense by capping the peptide N-terminus with a chiral residue. Our group has published a simple NMR method to report on the degree of the helical ratio obtained (h.r.) [2]. In the case of peptides 1 and 2 (Figure 1), the screw-sense induced in the helix depends not only on the configuration of the chiral N-terminal residue but also on whether it was tertiary (as in proteinogenic amino acid L-Val) or quaternary (L-a-methylvaline [L-(aMe)Val]) [3]. L-Val induces left-handed helicity in an oligo-Aib helix, while L-(aMe)Val induces right-handed helicity. This behaviour is in contrast with the right-handed screw sense preference for natural peptide helices made of C~a-trisubstituted L-amino acids.