title: Exploring the consequences of a representative "disallowed" conformation of Aib on a 3₁₀-helical fold.
abstract: The structural effects of a representative "disallowed" conformation of Aib on the 3(10)-helical fold of an octapeptidomimetic are explored. The 1D ((1)H, (13)C) & 2D NMR, FT-IR and CD data reveal that the octapeptide 1, adopts a 3(10)-helical conformation in solution, as it does in its crystal structure. The C-terminal methyl carboxylate (CO2Me) of 1 was modified into an 1,3-oxazine (Oxa) functional group in the peptidomimetic 2. This modification results in the stabilization of the backbone of the C-terminal Aib (Aib*-Oxa) of 2, in a conformation (ϕ, ψ = 180, 0) that is natively disallowed to Aib. Consequent to the presence of this natively disallowed conformation, the 3(10)-helical fold is not disrupted in the body of the peptidomimetic 2. But the structural distortions that do occur in 2 are primarily in residues in the immediate vicinity of the natively disallowed conformation, rather than in the whole peptide body. Non-native electronic effects resulting from modifications in backbone functional groups can be at the origin of stabilizing residues in natively disallowed conformations.
authors.affiliation: Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560012, Karnataka, India.
authors.forename: Shama
authors.initials: S
authors.lastname: Tumminakatti
authors.forename: Damodara N
authors.initials: DN
authors.lastname: Reddy
authors.forename: Erode N
authors.initials: EN
authors.lastname: Prabhakaran
mesh_terms: D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012996:Solutions / Q000737:chemistry
chemical_list: D010455:Peptides; D012996:Solutions
keywords: 310-helix; Aib rich peptides; disallowed conformations; electronic effects; oxazines; peptides; solution structure