The solid-state conformation of [Nle12]alpha-factor, the Saccharomyces cerevisiae tridecapeptide mating pheromone (WHWLQLKPGQPNleY), was investigated by 13C,15N rotational-echo double resonance (REDOR) nuclear magnetic resonance spectroscopy (NMR). Previous high-resolution NMR studies of [Nle12]alpha-factor in solution revealed a transient Type II beta-turn spanning residues 7-10 of the peptide. To investigate this region of [Nle12]alpha-factor in the solid state, a series of four selectively 13C,15N-enriched tridecapeptides were synthesized by solid-phase methods. Carbon-nitrogen distances between the labeled sites in lyophilized samples of [Nle12]alpha-factor were accurately measured by REDOR NMR. Experimentally determined distances were compared with those from calculated models for Type I and Type II beta-turns and for an extended chain. The measured distances indicate that, in a lyophilized powder, the central region of the [Nle12]alpha-factor is not in an extended conformation. The experimental data was most consistent with distances obtained from a distorted Type I beta-turn model.
The structural features of model N R -acetyl carboxyl-amide cyclic tetrapeptides with the sequence Xxx-Pro-Gly-Zzz where Xxx ) Lys, Orn, Dab, and Dpr; Zzz ) Glu and Asp (Dab, R, γ-diaminobutyric acid; Dpr, R,β-diaminopropionic acid) were studied to examine the influence of side chain lactamization on the stereochemical freedom of the backbone residues in i to i + 3 systems. Some of these cyclic peptides separate into distinct isomers at room temperature as evidenced by HPLC and NMR. Detailed analyses were carried out using 2D NMR and molecular modeling to unravel the structures of major conformers assumed by the cyclic peptides. Interproton distances obtained from ROESY spectra, amide proton temperature coefficients, backbone dihedral angles deduced from homonuclear coupling constants, and modeling studies (constrained annealing search, minimization, and dynamics simulations using the AMBER force field) suggest that in DMSO-d 6 solution these cyclic peptides adopt a variety of conformations that can be related to type II β-turns and γ-turns, but never to type I β-turns. The peptide backbone conformation, in this closely related series of cyclic peptides, is a function of the composition of the side chain but not the ring size.
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