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 o f NK-2 receptors. The conformational analysis of this peptide was cond ucted using nuclear magnetic resonance (NMR) and molecular dynamics. T his study improves understanding of the neurokinin ligand-receptor int eractions. Two-dimensional Homonuclear Hartmann-Hahn (2D-HOHAHA) and r otating frame Overhauser enhancement spectroscopy (2D-ROESY) were used to assign all the protons and to obtain through-space proton-proton i nteractions. ROE (rotating frame Overhauser enhancement) constraints m olecular dynamics were done to find the conformation which is consiste nt with the NMR data. Two betaI (or betaV') turns around Trp-2-Phe-3 a nd 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).