Tj. Siahaan et K. Lutz, CONFORMATIONAL STUDY OF CYCLO[GLN-TRP-PHE-GLY-LEU-MET] AS NK-2 ANTAGONIST BY NMR AND MOLECULAR-DYNAMICS, Journal of pharmaceutical and biomedical analysis, 12(1), 1994, pp. 65-71
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).