1420477-43-5Relevant articles and documents
The structural characterization of folded peptides containing the conformationally constrained β-amino acid residue β 2,2Ac6c
Basuroy, Krishnayan,Karuppiah, Vasantham,Shamala, Narayanaswamy,Balaram, Padmanabhan
, p. 2589 - 2603 (2013/03/13)
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 β2,2- disubstituted β-amino acid residue, 1-(aminomethyl)cyclohexanecarboxylic acid (β2,2Ac6c), have been structurally characterized in crystals by X-ray diffraction. The tripeptide Boc-Aib-β 2,2Ac6c-Aib-OMe (1) adopts a novel fold stabilized by two intramolecular H-bonds (C11 and C9) of opposite directionality. The tetrapeptide Boc-[Aib-β2,2Ac 6c]2-OMe (2) and pentapeptide Boc-[Aib-β 2,2Ac6c]2-Aib-OMe (3) form short stretches of a hybrid αβ C11 helix stabilized by two and three intramolecular H-bonds, respectively. The structure of the dipeptide Boc-Aib-β2,2Ac6c-OMe (5) does not reveal any intramolecular H-bond. The aggregation pattern in the crystal provides an example of an extended conformation of the β2,2Ac6c residue, forming a 'polar sheet' like H-bond. The protected derivative Ac-β2,2Ac6c-NHMe (4) adopts a locally folded gauche conformation about the Cβi?￡?C α bonds (θ=-55.7°). Of the seven examples of β2,2Ac6c residues reported here, six adopt gauche conformations, a feature which promotes local folding when incorporated into peptides. A comparison between the conformational properties of β2,2Ac6c and β3,3Ac6c 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. Copyright
