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A 3 10 ‐helical pentapeptide in water: Interplay of α,α‐disubstituted amino acids and the central residue on structure formation
Author(s) -
Wang Jia,
McElheny Dan,
Fu Yanwen,
Li Guangyu,
Kim Joohyun,
Zhou Zhe,
Wu Ling,
Keiderling Timothy A.,
Hammer Robert P.
Publication year - 2009
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21258
Subject(s) - chemistry , pentapeptide repeat , peptide , amino acid , stereochemistry , side chain , folding (dsp implementation) , steric effects , hydrogen bond , residue (chemistry) , aqueous solution , norvaline , nuclear magnetic resonance spectroscopy , imino acid , crystallography , molecule , proline , organic chemistry , polymer , valine , biochemistry , electrical engineering , engineering
C α,α ‐disubstituted amino acids (ααAAs) are widely used to conformationally constrain peptides. A series of pentapeptides containing dipropylglycine (Dpg) at alternating positions and their α‐amino acid counterpart L ‐norvaline (Nva) analogues were synthesized to fully investigate the impact of Dpg on peptide backbone structure in aqueous solution. CD, VCD, and NMR spectral analysis suggest that Dpg containing peptides adopt more ordered structures relative to their Nva containing analogues. The central residues (Ala, Thr, Tyr, Val) and the charged side‐chains of Glu and Lys play important roles in the degree of peptide folding. Hydrophobic and branched residues (Val, Tyr) at the central position of the peptide produce greater folding as judged by CD and NMR. Variation of the chemical shift with temperature (Δδ/Δ T NH) of Ac‐Glu‐Dpg‐Tyr‐Dpg‐Lys‐NH 2 suggests a series of i → i + 3 hydrogen bonds between the N‐terminal acetyl carbonyl and the Tyr 3 NH, and the Glu 1 carbonyl and the Dpg 4 NH. The solution conformation of Ac‐Glu‐Dpg‐Tyr‐Dpg‐Lys‐NH 2 calculated from NMR‐derived constraints shows a 3 10 ‐helical structure (two repetitive type‐III β‐turns) at residues 1‐4, which is supported by 2D NMR, CD, and VCD spectra. Analysis of NMR‐derived models of these peptides suggest that there is a strong hydrophobic interaction of the pro‐ S propyl side chain of Dpg 2 and the Tyr 3 side‐chain that may be a strong stabilizing force of the peptide folding in water. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 452–464, 2009. 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