Chiral interaction in peptide molecules: Effects of chiral peptide species on helix‐sense induction in an N‐terminal‐free achiral peptide

Noncovalent chiral domino effect (NCDE) has been proposed as terminal‐specific interaction upon a 3 10 ‐helical peptide chain, of which the helix sense is manipulated by an external chiral stimulus (mainly amino acid derivatives) operating on the N‐terminus (Inai, Y., et al. J Am Chem Soc 2000, 122, 11731–11732; ibid. , 2002, 124, 2466–2473; ibid. , 2003, 125, 8151–8162). We have investigated here a helix‐sense induction in an optically inactive N‐terminal‐free nonapeptide ( 1 ) through the screening of several peptide species that differ in chiral sequence, chain length, and C‐terminal group. Helix‐sense induction in peptide 1 depends largely on both the C‐terminal chirality and carboxyl group in the external peptide, in which N‐carbonyl‐blocked amino acids, “monopeptide acids,” should be the minimum requirement for effective induction. N‐Protected mono‐ to tetrapeptides of L ‐Leu residue commonly induce a right‐handed helix. NMR study and theoretical computation reveal that the N‐terminal segment of peptide 1 binds the N‐protected dipeptide molecule through multipoint coordination to induce a right‐handed helix preferentially. The present findings not only will improve our understanding of the chiral roles in peptide or protein helical termini, but also might demonstrate potential applications to chirality‐responsive materials based on peptide helical fragments. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 471–481, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com