%0 Journal Article
%@ 0006291X
%A Bhadbhade, M.Mohan
%A Kishore, Raghuvansh
%D 2004
%F open:950
%I Elsevier Science
%J Biochemical and Biophysical Research Communications
%K β-Ala containing peptide; X-ray diffraction analysis; Non-superimposable stereogeometrical features; Folded–unfolded β-Ala conformation
%N 4
%P 1029-1036
%T An observation of non-superimposable stereogeometrical features in a non-chiral one-component β-Ala model peptide
%U http://crdd.osdd.net/open/950/
%V 316
%X This paper describes the chemical synthesis and crystal molecular conformation of a non-chiral β-Ala containing model peptide Boc-β-Ala-Acc5-OCH3. The analysis revealed the existence of two crystallographically independent molecules A and B, in the asymmetric unit. Unexpectedly, while the magnitudes of the backbone torsion angles in both molecules are remarkably similar, the signs of the corresponding torsion angles are reverse therefore, inclining us to suggest the existence of non-superimposable stereogeometrical features in a non-chiral one-component β-Ala model system. The critical μ torsion angle around CβH2–CαH2 bond of the β-Ala residue represents a typical gauche orientation i.e., μ=67.7° in A and μ=−61.2° in B, providing the molecule an overall crescent shaped topology. The observed conformation contrasts markedly to those determined for the correlated non-chiral model peptides: Boc-β-Ala-Acc6-OCH3 and Boc-β-Ala-Aib-OCH3 signifying the role of stereocontrolling elements since the stereochemically constrained Cα,α-disubstituted glycyl residues (e.g., Acc5, Acc6, and the prototype Aib) are known to strongly restrict the peptide backbone conformations in the 310/α-helical-regions (φ≈±60 ±20°, ψ≈±30 ±20°) of the Ramachandran map. Unpredictably, the preferred, φ,ψ torsion angles of the Acc5 residue fall outside the helical regions of the Ramachandran map and exhibit opposite-handed twists for A and B. The implications of the semi-extended conformation of the Acc5 residue in the construction of backbone-modified novel scaffolds and peptides of biological relevance are highlighted. Taken together, the results indicate that in short linear β-Ala containing peptides specific structural changes can be induced by selective substitution of non-coded linear- or cyclic symmetrically Cα,α-disubstituted glycines, reinstating the hypothesis that in addition to conformational restrictions, the chemical nature of the neighboring side-chain substituents and local environments collectively influences the stabilization of folding–unfolding behavior of the two methylene units of a β-Ala residue.
%Z Copyright of this article belongs to Elsevier Science.