Chirality and Template-Mediated Induction of Helical Preferences in Achiral [beta]-Peptides

• Published in: Chemistry : a European journal 2012-12, Vol.18 (50), p.16046
• Main Authors: Sharma, Gangavaram V. M, Kodeti, Srinivas Reddy, Dutta, Samit K, Velaparthi, Subash, Narsimulu, Kongari, Anjaiah, Gonuguntla, Basha, Shaik Jeelani, Kunwar, Ajit C
• Format: Article
• Language: English
• Subjects: Amino acids; Beta; Chemistry; Peptides; Proteins
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201201892

This study describes chirality- or template-mediated helical induction in achiral [beta]-peptides for the first time. A strategy of end capping [beta]-peptides derived from [beta]-hGly (the smallest achiral [beta]-amino acid) with a chiral [beta]-amino acid that possesses a carbohydrate side chain ([beta]-Caa; C-linked carbo [beta]-amino acid) or a small, robust helical template derived from [beta]-Caas, was adopted to investigate folding propensity. A single chiral (R)-[beta]-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 [beta]-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 [beta]-hGly moieties due to chirality. Additionally, the [beta]-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 [beta]-peptides is a very attractive strategy. [PUBLICATION ABSTRACT]