title: Unusual folding propensity of an unsubstituted β,γ-hybrid model peptide: importance of the C-H⋅⋅⋅O intramolecular hydrogen bond.
abstract: The single-crystal X-ray diffraction analysis of a β,γ-hybrid model peptide Boc-β-Ala-γ-Abu-NH2 revealed the existence of four crystallographically independent molecules (A, B, C and D conformers) in the asymmetric unit. The analysis revealed that unusual β-turn-like folded structures predominate, wherein the conformational space of non-proteinogenic β-Ala and γ-Abu residues are restricted to gauche-gauche-skew and skew-gauche-trans-skew orientations, respectively. Interestingly, the U-shaped conformers are seemingly stabilised by an effective unconventional C-H⋅⋅⋅O intramolecular hydrogen bond, encompassing a non-covalent 14-membered ring-motif. Taking into account the signs of torsion angles, these conformers could be grouped into two distinct categories, A/B and C/D, establishing the incidence of non-superimposable stereogeometrical features across a non-chiral one-component peptide model system, that is, "mirror-image-like" relationships. The natural occurrence of β-Ala and γ-Abu entities in various pharmacologically important molecules, coupled with their biocompatibilities, highlight how the non-functionalised β,γ-hybrid segment may offer unique advantages for introducing and/or manipulating a wide spectrum of biologically relevant hydrogen bonded secondary structural mimics in short synthetic peptides.
authors.affiliation: Department of Chemistry, Panjab University, Sector 14, Chandigarh-160 014, India.
authors.forename: Paloth
authors.initials: P
authors.lastname: Venugopalan
authors.forename: Raghuvansh
authors.initials: R
authors.lastname: Kishore
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: C585399:Boc-beta-Ala-gamma-Abu-NH2; D009842:Oligopeptides
keywords: X-ray diffraction; hydrogen bonds; peptides; peptidomimetics; unsubstituted hybrid peptides