En route towards the peptide γ‐helix: X‐ray diffraction analyses and conformational energy calculations of Adm‐rich short peptides

We performed the solution‐phase synthesis of a set of model peptides, including homo‐oligomers, based on the 2‐aminoadamantane‐2‐carboxylic acid (Adm) residue, an extremely bulky, highly lipophilic, tricyclic, achiral, Cα‐tetrasubstituted α‐amino acid. In particular, for the difficult peptide coupling reaction between two Adm residues, we took advantage of the Meldal's α‐azidoacyl chloride approach. Most of the synthesized Adm peptides were characterized by single‐crystal X‐ray diffraction analyses. The results indicate a significant propensity for the Adm residue to adopt γ‐turn and γ‐turn‐like conformations. Interestingly, we found that a ‐CO‐(Adm)2‐NH‐ sequence is folded in the crystal state into a regular, incipient γ‐helix, at variance with the behavior of all of the homo‐dipeptides from Cα‐tetrasubstituted α‐amino acids already investigated, which tend to adopt either the β‐turn or the fully extended conformation. Our density functional theory conformational energy calculations on the terminally blocked homo‐peptides (n = 2–8) fully confirmed the crystal‐state data, strongly supporting the view that this rigid Cα‐tetrasubstituted α‐amino acid residue is largely the most effective building block for γ‐helix induction, although to a limited length (anti‐cooperative effect). Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

2‐Aminoadamantane‐2‐carboxylic acid (Adm) was p...

Source: Journal of Peptide Science - October 31, 2016 Category: Biochemistry Authors: Daniela Mazzier, Luigi Grassi, Alessandro Moretto, Carlos Alem án, Fernando Formaggio, Claudio Toniolo, Marco Crisma Tags: Special Issue Article Source Type: research