title: The side-chain hydroxy groups of a cyclic α,α-disubstituted α-amino acid promote oligopeptide 310 -helix packing in the crystalline state.
abstract: 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)-Ac5 c(dOMOM) ], or side-chain hydroxy groups, (3S,4S)-1-amino-(3,4-dihydroxy)cyclopentanecarboxylic acid [(S, S)-Ac5 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)-Ac5 c(dOMOM) ]-(Aib)4 -OEt (1), Cbz-[(S, S)-Ac5 c(dOH) ]-(Aib)4 -OEt (2), Cbz-(Aib)4 -[(S, S)-Ac5 c(dOMOM) ]-OMe (3), and Cbz-(Aib)4 -[(S, S)-Ac5 c(dOH) ]-OMe (4). We then analyzed the peptides' structures in the crystalline state. The four peptides all folded into 310 -helical structures; 1 formed a left-handed (M) 310 -helix, 2 formed a mixture of right-handed (P) and (M) 310 -helices, 3 formed a mixture of (P) and (M) 310 -helices, and 4 formed a (P) 310 -helix, respectively. In packing mode, the molecules of peptides 1 and 3, which both possessed an Ac5 c(dOMOM) residue, were connected by intermolecular hydrogen bonds along the peptide backbone (NH···O type). On the other hand, the packing of peptides 2 and 4, which both contained an Ac5 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 Ac5 c(dOH) (OH···O type). © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 757-768, 2016.
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, Tokyo, 158-8501, Japan. demizu@nihs.go.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Demizu
authors.affiliation: Osaka University of Pharmaceutical Sciences, Osaka, 569-1094, Japan.
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Doi
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, Tokyo, 158-8501, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, Tokyo, 158-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Misawa
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-Machi, Nagasaki, 852-8521, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Oba
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, Tokyo, 158-8501, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kurihara
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suemune
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-Machi, Nagasaki, 852-8521, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D009842:Oligopeptides
keywords: X-ray diffraction; helical structure; peptide; α,α-disubstituted amino acid