New Helical Folds in α-Peptides with Alternating Chirality

• Published in: Chemistry : a European journal 2014-09, Vol.20 (36), p.11428-11438
• Main Authors: Sharma, Gangavaram V. M., Venkateshwarlu, Gajulapati, Reddy, Pothula Purushotham, Kunwar, Ajit C.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Capping; Chirality; Helical; helical induction; helical structures; Helices; hybrid structures; Models, Molecular; Molecular Sequence Data; NMR spectroscopy; Nuclear Magnetic Resonance, Biomolecular; Peptides; Peptides - chemistry; Protein Structure, Secondary; Stereoisomerism; Strategy; Strings
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201403164

In α‐peptides, the 8/10 helix is theoretically predicted to be energetically unstable and has not been experimentally observed so far. Based on our earlier studies on ‘helical induction’ and ‘hybrid helices’, we have adopted the ‘end‐capping’ strategy to induce the 8/10 helix in α‐peptides by using short α/β‐peptides. Thus, α‐peptides containing a regular string of α‐amino acids with alternating chirality were end capped by α/β‐peptides with 11/9‐helical motifs at the termini. Extensive NMR spectroscopy studies of these peptides revealed the presence of a hitherto unknown 8/10‐helical pattern; the H‐bonds in the shorter pseudorings were rather weak. The approach of using short helical motifs to induce new mixed helices in α‐peptides could provide avenues for more versatile design strategies. A new twist: α‐Peptides containing a regular string of α‐amino acids with alternating chirality were end capped by α/β‐peptides with 11/9‐helical motifs at the termini. Extensive NMR spectroscopy studies of these peptides revealed the presence of a hitherto unknown 8/10‐helical pattern in this hybrid helix (see figure); the H‐bonds in the shorter pseudorings were rather weak. The addition of helix‐stabilizing influences may enhance the propensity and stability of these uncommon folding patterns in oligomers of α‐amino acids.