Aib-rich side chain lactam-bridged oligomers Ac-(Glu-Aib-Aib-Lys)n-Ala-OH, with n=1, 2, 3, were designed and synthesized as putative models of the 310-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 310-helix. The NMR results clearly indicate that there is an increase of 310-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 310-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 310-helix. Identification of the hydrogen-bond pattern indicate that CdO(i)- - -HN(i+3) hydrogen bonds, typical of the 310-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 310-helix.

Aib-Rich Peptides Containing Lactam-Bridged Side-Chains as Models of the 3/10 Helix

SCHIEVANO, ELISABETTA;MAMMI, STEFANO;PEGGION, EVARISTO
2001

Abstract

Aib-rich side chain lactam-bridged oligomers Ac-(Glu-Aib-Aib-Lys)n-Ala-OH, with n=1, 2, 3, were designed and synthesized as putative models of the 310-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 310-helix. The NMR results clearly indicate that there is an increase of 310-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 310-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 310-helix. Identification of the hydrogen-bond pattern indicate that CdO(i)- - -HN(i+3) hydrogen bonds, typical of the 310-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 310-helix.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/2467712
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