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The side‐chain hydroxy groups of a cyclic α,α‐disubstituted α‐amino acid promote oligopeptide 3 10 ‐helix packing in the crystalline state
Author(s) -
Demizu Yosuke,
Doi Mitsunobu,
Yamashita Hiroko,
Misawa Takashi,
Oba Makoto,
Kurihara Masaaki,
Suemune Hiroshi,
Tanaka Masakazu
Publication year - 2016
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.22881
Subject(s) - chemistry , tetrapeptide , hydrogen bond , side chain , stereochemistry , helix (gastropod) , residue (chemistry) , oligopeptide , peptide , amino acid , intermolecular force , crystallography , molecule , organic chemistry , biochemistry , ecology , snail , biology , polymer
A single chiral cyclic α,α‐disubstituted amino acid with side‐chain methoxymethyl (MOM) protecting groups, (3S,4S)−1‐amino‐(3,4‐dimethoxymethoxy)cyclopentanecarboxylic acid [(S, S)‐Ac 5 c dOMOM ], or side‐chain hydroxy groups, (3S,4S)−1‐amino‐(3,4‐dihydroxy)cyclopentanecarboxylic acid [(S, S)‐Ac 5 c dOH ], was attached to the N‐terminal or C‐terminal position of α‐aminoisobutyric acid (Aib) tetrapeptide segments; i.e., we designed and synthesized four pentapeptides, Cbz‐[(S, S)‐Ac 5 c dOMOM ]‐(Aib) 4 ‐OEt ( 1 ), Cbz‐[(S, S)‐Ac 5 c dOH ]‐(Aib) 4 ‐OEt ( 2 ), Cbz‐(Aib) 4 ‐[(S, S)‐Ac 5 c dOMOM ]‐OMe ( 3 ), and Cbz‐(Aib) 4 ‐[(S, S)‐Ac 5 c dOH ]‐OMe ( 4 ). We then analyzed the peptides’ structures in the crystalline state. The four peptides all folded into 3 10 ‐helical structures; 1 formed a left‐handed (M) 3 10 ‐helix, 2 formed a mixture of right‐handed (P) and (M) 3 10 ‐helices, 3 formed a mixture of (P) and (M) 3 10 ‐helices, and 4 formed a (P) 3 10 ‐helix, respectively. In packing mode, the molecules of peptides 1 and 3 , which both possessed an Ac 5 c dOMOM residue, were connected by intermolecular hydrogen bonds along the peptide backbone (NH···O type). On the other hand, the packing of peptides 2 and 4 , which both contained an Ac 5 c dOH residue, was based on intermolecular hydrogen bonds derived from both the peptide backbone and the side‐chain hydroxy groups of the amino acid Ac 5 c dOH (OH···O type). © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 757–768, 2016.