The Structural Characterization of Folded Peptides Containing the Conformationally Constrained beta-Amino Acid Residue beta(2,2)Ac(6)c


Autoria(s): Basuroy, Krishnayan; Karuppiah, Vasantham; Shamala, Narayanaswamy; Balaram, Padmanabhan
Data(s)

2012

Resumo

Backbone alkylation has been shown to result in a dramatic reduction in the conformational space that is sterically accessible to a-amino acid residues in peptides. By extension, the presence of geminal dialkyl substituents at backbone atoms also restricts available conformational space for beta and ? residues. Five peptides containing the achiral beta 2,2-disubstituted beta-amino acid residue, 1-(aminomethyl)cyclohexanecarboxylic acid (beta 2,2Ac6c), have been structurally characterized in crystals by X-ray diffraction. The tripeptide Boc-Aib-beta 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-beta 2,2Ac6c]2-OMe (2) and pentapeptide Boc-Aib-beta 2,2Ac6c]2-Aib-OMe (3) form short stretches of a hybrid a beta C11 helix stabilized by two and three intramolecular H-bonds, respectively. The structure of the dipeptide Boc-Aib-beta 2,2Ac6c-OMe (5) does not reveal any intramolecular H-bond. The aggregation pattern in the crystal provides an example of an extended conformation of the beta 2,2Ac6c residue, forming a polar sheet like H-bond. The protected derivative Ac-beta 2,2Ac6c-NHMe (4) adopts a locally folded gauche conformation about the C beta?Ca bonds (?=-55.7 degrees). Of the seven examples of beta 2,2Ac6c residues reported here, six adopt gauche conformations, a feature which promotes local folding when incorporated into peptides. A comparison between the conformational properties of beta 2,2Ac6c and beta 3,3Ac6c residues, in peptides, is presented. Backbone torsional parameters of H-bonded a beta/beta a turns are derived from the structures presented in this study and earlier reports.

Formato

application/pdf

Identificador

http://eprints.iisc.ernet.in/45674/1/hel_chi_act_95-12_2589_2012.pdf

Basuroy, Krishnayan and Karuppiah, Vasantham and Shamala, Narayanaswamy and Balaram, Padmanabhan (2012) The Structural Characterization of Folded Peptides Containing the Conformationally Constrained beta-Amino Acid Residue beta(2,2)Ac(6)c. In: HELVETICA CHIMICA ACTA, 95 (12). pp. 2589-2603.

Publicador

WILEY-V C H VERLAG GMBH

Relação

http://dx.doi.org/10.1002/hlca.201200537

http://eprints.iisc.ernet.in/45674/

Palavras-Chave #Molecular Biophysics Unit #Physics
Tipo

Journal Article

PeerReviewed