title: The 2.0₅-helix in hetero-oligopeptides entirely composed of C(α,α)-disubstituted glycines with both side chains longer than methyls.
abstract: The existence of the very uncommon, but potentially quite interesting, multiple, consecutive fully-extended conformation (2.0₅-helix) has been already clearly demonstrated in homo-oligopeptides based on quaternary α-amino acids with both side chains longer than methyls, but not cyclized on the α-carbon atom. To extend the scope of this research, in this work we investigated the occurrence of this flat 3D-structure in hetero-oligopeptides, each composed of two or three different residues of that class. The synthesis of a terminally protected peptide series to the tetrapeptide level was carried out by solution methods. The resulting oligomers were chemically and conformationally characterized. The data obtained point to an overwhelming population of the fully-extended conformation in CDCl3. However, a solvent-driven switch to a predominant 3₁₀-helical structure was seen in CD3CN. A delicate, local balance between these two conformations is confirmed to occur in the crystalline state. Molecular dynamics simulations in CHCl3 on a hetero-tetrapeptide converged to the fully-extended conformation even starting from the 3₁₀-helical structure.
authors.affiliation: Department of Chemistry, ICB, Padova Unit, CNR, University of Padova, 35131, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Crisma
authors.forename: Cristina
authors.initials: C
authors.lastname: Peggion
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretto
authors.forename: Raja
authors.initials: R
authors.lastname: Banerjee
authors.forename: Subhrangshu
authors.initials: S
authors.lastname: Supakar
authors.forename: Fernando
authors.initials: F
authors.lastname: Formaggio
authors.forename: Claudio
authors.initials: C
authors.lastname: Toniolo
mesh_terms: D018360:Crystallography, X-Ray; D005998:Glycine / Q000737:chemistry*; D006860:Hydrogen Bonding; D008745:Methylation; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors
chemical_list: D009842:Oligopeptides; D012996:Solutions; D005998:Glycine
keywords: Cα-tetrasubstituted α-amino acids; IR absorption; NMR; X-ray diffraction; molecular dynamics simulations; peptide conformation