Premium
A helical arrangement of β‐substituents of dehydropeptides: Synthesis and conformational study of sequential nona‐ and dodecapeptides possessing ( Z )‐β‐(1‐naphthyl)dehydroalanine residues
Author(s) -
Inai Yoshihito,
Hirabayashi Tadamichi
Publication year - 2001
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/1097-0282(20011015)59:5<356::aid-bip1033>3.0.co;2-1
Subject(s) - chemistry , crystallography , stereochemistry , helix (gastropod) , two dimensional nuclear magnetic resonance spectroscopy , nuclear overhauser effect , dehydroalanine , pseudorotation , proton nmr , peptide , side chain , nuclear magnetic resonance spectroscopy , molecule , biochemistry , organic chemistry , snail , ecology , biology , polymer
Sequential nona‐ and dodecapeptides possessing three and four ( Z )‐β ‐(1‐naphthyl)dehydroalanine (Δ Z Nap) residues, Boc–( L ‐Ala–Δ Z Nap– L ‐Leu) n –OCH 3 ( n = 3 and 4; Boc = t ‐butoxycarbonyl), were synthesized to design a rigid 3 10 ‐helical backbone for a regular arrangement of functional groups using dehydropeptides. Their solution conformations were investigated by NMR and CD analyses, and theoretical energy calculations. Both peptides were found to adopt a 3 10 ‐helical conformation in CDCl 3 from their nuclear Overhauser effect spectroscopy (NOESY) spectra, which showed intense cross peaks for N i H–N i +1 H proton pairs, but no cross peaks for C α i H–N i +4 H pairs. The predominance of a 3 10 ‐helix was also supported by solvent accessibility of NH resonances. CD spectra of both peptides in tetrahydrofuran showed strong exciton couplets at around 228 nm assignable to naphthyl side chains, which are regularly arranged along a right‐handed helical backbone. Chain‐length effects on conformational preference in sequential peptide –(Ala–Δ Z Nap–Leu) n – were discussed based on spectroscopic analysis, energy minimization, and molecular dynamics simulations. Consequently, the repeating number n ≥ 3 forms predominantly a right‐handed 3 10 ‐helical conformation. The energy calculation also revealed that the midpoint naphthyl groups of peptide n = 4 are highly restricted to one stable orientation. In conclusion, β‐substituted α,β‐dehydroalanine is expected to be a unique tool for designing a rigid molecular frame of 3 10 ‐helix along which β‐functional groups are regularly arranged in a specific manner. © 2001 John Wiley & Sons, Inc. Biopolymers 59: 356–369, 2001