title: En route towards the peptide γ-helix: X-ray diffraction analyses and conformational energy calculations of Adm-rich short peptides.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Padova, 35131, Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mazzier
authors.affiliation: Department of Chemistry, University of Padova, 35131, Padova, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Grassi
authors.affiliation: Department of Chemistry, University of Padova, 35131, Padova, Italy.|Institute of Biomolecular Chemistry, Padova Unit, CNR, 35131, Padova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretto
authors.affiliation: Departament d'Enginyeria Quimica, ETSEIB, Universitat Politècnica de Catalunya, 08028, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Alemán
authors.affiliation: Department of Chemistry, University of Padova, 35131, Padova, Italy.|Institute of Biomolecular Chemistry, Padova Unit, CNR, 35131, Padova, Italy.
authors.forename: Fernando
authors.initials: F
authors.lastname: Formaggio
authors.affiliation: Department of Chemistry, University of Padova, 35131, Padova, Italy.|Institute of Biomolecular Chemistry, Padova Unit, CNR, 35131, Padova, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Toniolo
authors.affiliation: Institute of Biomolecular Chemistry, Padova Unit, CNR, 35131, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Crisma
mesh_terms: D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D011789:Quantum Theory; D012996:Solutions
chemical_list: D010455:Peptides; D012996:Solutions
keywords: Adm peptides; X-ray diffraction; conformational energy calculations; γ-helix; γ-turns