Conformational study of cyclo[Gln-Trp-Phe-Gly-Leu-Met] as NK-2 antagonist by NMR and molecular dynamics.

Cyclo[Gln-Trp-Phe-Gly-Leu-Met] (1) is a selective peptide antagonist of NK-2 receptors. The conformational analysis of this peptide was conducted using nuclear magnetic resonance (NMR) and molecular dynamics. This study improves understanding of the neurokinin ligand-receptor interactions. Two-dimensional Homonuclear Hartmann-Hahn (2D-HOHAHA) and rotating frame Overhauser enhancement spectroscopy (2D-ROESY) were used to assign all the protons and to obtain through-space proton-proton interactions. ROE (rotating frame Overhauser enhancement) constraints molecular dynamics were done to find the conformation which is consistent with the NMR data. Two beta I (or beta V') turns around Trp-2-Phe-3 and around Leu-5-Met-6 are found in this peptide which are represented by models. The conformation of this peptide is also compared with the non-peptide NK-2 antagonist SR-48968 (2).