title: Chirality and template-mediated induction of helical preferences in achiral β-peptides.
abstract: This study describes chirality- or template-mediated helical induction in achiral β-peptides for the first time. A strategy of end capping β-peptides derived from β-hGly (the smallest achiral β-amino acid) with a chiral β-amino acid that possesses a carbohydrate side chain (β-Caa; C-linked carbo β-amino acid) or a small, robust helical template derived from β-Caas, was adopted to investigate folding propensity. A single chiral (R)-β-Caa residue at the C- or N-terminus in these oligomers led to a preponderance of right-handed 12/10-helical folds, which was reiterated more strongly in peptides capped at both the C- and N-terminus. Likewise, the presence of a template (a 12/10-helical trimer) at both the C- and N-terminus resulted in a very robust helix. The propagation of the helical fold and its sustenance was found in a homo-oligomeric sequence with as many as seven β-hGly residues. In both cases, the induction of helicity was stronger from the N terminus, whereas an anchor at the C terminus resulted in reduced helical propensity. Although these oligomers have been theoretically predicted to favor a 12/10-mixed helix in apolar solvents, this study provides the first experimental evidence for their existence. Diastereotopicity was found in both the methylene groups of the β-hGly moieties due to chirality. Additionally, the β-hGly units have shown split behavior in the conformational space to accommodate the 12/10-helix. Thus, end capping to assist chiralty- or template-mediated helical induction and stabilization in achiral β-peptides is a very attractive strategy.
authors.affiliation: Organic and Biomolecular Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. esmvee@iict.res.in
authors.forename: Gangavaram V M
authors.initials: GV
authors.lastname: Sharma
authors.forename: Srinivas Reddy
authors.initials: SR
authors.lastname: Kodeti
authors.forename: Samit K
authors.initials: SK
authors.lastname: Dutta
authors.forename: Subash
authors.initials: S
authors.lastname: Velaparthi
authors.forename: Kongari
authors.initials: K
authors.lastname: Narsimulu
authors.forename: Gonuguntla
authors.initials: G
authors.lastname: Anjaiah
authors.forename: Shaik
authors.initials: S
authors.lastname: Jeelani Basha
authors.forename: Ajit C
authors.initials: AC
authors.lastname: Kunwar
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D010455:Peptides; D005998:Glycine