Amino equatorial effect of a six-membered ring amino acid on its peptide 310- and α-helices

TETRAHEDRON

卷:71

Article

Hirata, Takayuki¹  Ueda, Atsushi²  Oba, Makoto²  Doi, Mitsunobu³  Demizu, Yosuke⁴  Kurihara, Masaaki⁴  Nagano, Masanobu¹  Suemune, Hiroshi¹  Tanaka, Masakazu² 

[1] Kyushu Univ, Grad Sch Pharmaceut Sci, Fukuoka 8128582, Japan

[2] Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki 8528521, Japan

[3] Osaka Univ Pharmaceut Sci, Osaka 5691094, Japan

[4] Natl Inst Hlth Sci, Tokyo 1588501, Japan

关键词: Amino acids;    Chirality;    Conformation analysis;    Helical structures;    Peptides;   

DOI  :  10.1016/j.tet.2015.02.075

来源: Elsevier

【 摘 要 】

Two diastereomeric six-membered ring alpha,alpha-disubstituted alpha-amino acids (1R,3R)- and (1S,3R)-1-amino-3-methylcyclohexanecarboxylic acids (Ac(6)c(3M)); side-chain restricted leucine analogs, were stereoselectively synthesized from (3R)-3-methylcyclohexanone by a Bucherer-Bergs or Strecker reaction. Two series of homo-chiral homopeptides Cbz-[(1R,3R)- and (1S,3R)-Ac(6)c(3M)](n)-OMe, up to hexapeptides (n=6), were prepared, respectively, and the preferred conformations of cyclohexane rings of amino acid residues and the peptide-backbones were studied. In solution, these peptides formed helical structures, but the helical-screw control to one-handedness was not possible for the hexapeptide length. In the crystal state, all (1R,3R)-Ac(6)c(3M) residues formed cyclohexane chair form conformations with a 3-methyl substituent at equatorial orientation and an amino group at the axial position, whereas all (15,3R)-Ac(6)c(3M) residues assumed cyclohexane chair forms with the 3-methyl and amino groups at equatorial orientations. The preferred peptide-backbone structure of (1R,3R)-Ac(6)c(3M) hexapeptide had (P) and (M) 3(10)-helices, and that of (1S,3R)-Ac(6)c(3M) hexapeptide had (P) and (M) alpha-helices in the crystal state. (C) 2015 Elsevier Ltd. All rights reserved.

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