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The Structural Characterization of Folded Peptides Containing the Conformationally Constrained β ‐Amino Acid Residue β 2,2 Ac 6 c
Author(s) -
Basuroy Krishnayan,
Karuppiah Vasantham,
Shamala Narayanaswamy,
Balaram Padmanabhan
Publication year - 2012
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201200537
Subject(s) - chemistry , intramolecular force , stereochemistry , dipeptide , tetrapeptide , pentapeptide repeat , tripeptide , crystal structure , steric effects , hydrogen bond , amino acid , crystallography , peptide , molecule , biochemistry , organic chemistry
Backbone alkylation has been shown to result in a dramatic reduction in the conformational space that is sterically accessible to α ‐amino acid residues in peptides. By extension, the presence of geminal dialkyl substituents at backbone atoms also restricts available conformational space for β and γ residues. Five peptides containing the achiral β 2,2 ‐disubstituted β‐ amino acid residue, 1‐(aminomethyl)cyclohexanecarboxylic acid ( β 2,2 Ac 6 c), have been structurally characterized in crystals by X‐ray diffraction. The tripeptide Boc‐Aib‐ β 2,2 Ac 6 c‐Aib‐OMe ( 1 ) adopts a novel fold stabilized by two intramolecular H‐bonds (C 11 and C 9 ) of opposite directionality. The tetrapeptide Boc‐[Aib‐ β 2,2 Ac 6 c] 2 ‐OMe ( 2 ) and pentapeptide Boc‐[Aib‐ β 2,2 Ac 6 c] 2 ‐Aib‐OMe ( 3 ) form short stretches of a hybrid αβ C 11 helix stabilized by two and three intramolecular H‐bonds, respectively. The structure of the dipeptide Boc‐Aib‐ β 2,2 Ac 6 c‐OMe ( 5 ) does not reveal any intramolecular H‐bond. The aggregation pattern in the crystal provides an example of an extended conformation of the β 2,2 Ac 6 c residue, forming a ‘polar sheet’ like H‐bond. The protected derivative Ac‐ β 2,2 Ac 6 c‐NHMe ( 4 ) adopts a locally folded gauche conformation about the C β C α bonds ( θ =−55.7°). Of the seven examples of β 2,2 Ac 6 c residues reported here, six adopt gauche conformations, a feature which promotes local folding when incorporated into peptides. A comparison between the conformational properties of β 2,2 Ac 6 c and β 3,3 Ac 6 c residues, in peptides, is presented. Backbone torsional parameters of H‐bonded αβ / βα turns are derived from the structures presented in this study and earlier reports.