title: Aib-rich peptides containing lactam-bridged side chains as models of the 3(10)-helix.
abstract: Aib-rich side chain lactam-bridged oligomers with n =1, 2, 3, were designed and synthesized as putative models of the 3(10)-helix. These peptides were conformationally characterized in aqueous solution containing SDS micelles by CD, NMR, and computer simulations. The lactam bridge between the side chains of L-Glu and L-Lys in (i) and (i+3) positions was introduced in order to enhance the conformational preference toward the right-handed 3(10)-helix. The NMR results clearly indicate that there is an increase of 3(10)-helix formation upon chain elongation. In the dimer and trimer (n = 2 and n = 3, respectively, in the structure reported above) the observed NOE connectivities are compatible with the 3(10)-helical arrangement, confirmed by the temperature coefficients of the amide proton resonances which suggest the presence of a hydrogen-bonded structure. The phi and psi dihedral angles of the structures obtained by molecular dynamics calculations are also compatible with the 3(10)-helix. Identification of the hydrogen-bond pattern indicate that C=O(i)- - -HN(i+3) hydrogen bonds, typical of the 3(10)-helical conformation, are highly probable in all low-energy structures. The CD spectra of these Aib-rich lactam-bridged oligopeptides, obtained in the same solvent system used for NMR experiments, provide important insight into the spectroscopic characteristics of the 3(10)-helix.
authors.affiliation: University of Padova, Department of Organic Chemistry, Biopolymer Research Center, C.N.R, Via Marzolo 1, 35131 Padua, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Schievano
authors.forename: A
authors.initials: A
authors.lastname: Bisello
authors.forename: M
authors.initials: M
authors.lastname: Chorev
authors.forename: A
authors.initials: A
authors.lastname: Bisol
authors.forename: S
authors.initials: S
authors.lastname: Mammi
authors.forename: E
authors.initials: E
authors.lastname: Peggion
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D002942:Circular Dichroism; D007769:Lactams / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012996:Solutions / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D007769:Lactams; D010455:Peptides; D012996:Solutions