title: Conformational study of cyclo[Gln-Trp-Phe-Gly-Leu-Met] as NK-2 antagonist by NMR and molecular dynamics.
abstract: 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).
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
authors.forename: T J
authors.initials: TJ
authors.lastname: Siahaan
authors.forename: K
authors.initials: K
authors.lastname: Lutz
mesh_terms: D000595:Amino Acid Sequence; D001549:Benzamides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D010456:Peptides, Cyclic / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry; D011487:Protein Conformation; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D015320:Tachykinins / Q000037:antagonists & inhibitors*
chemical_list: D001549:Benzamides; D010456:Peptides, Cyclic; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C073361:cyclo(Gln-Trp-Phe-Gly-Leu-Met); C073839:SR 48968; D015288:Neurokinin A