title: Conformation of the tripeptide Cbz-Pro-Leu-Trp-OBzl(CF3)2 deduced from two-dimensional 1H-NMR and conformational energy calculations is related to its affinity for NK1-receptor.
abstract: Chemical modifications of dual NK1/NK2 ligand Cbz-Gly-Leu-Trp-OBzl(CF3)2 (1) enabled us to create a high NK1 selective ligand Cbz-Pro-Leu-Trp-OBzl(CF3)2 (2). A determination of the conformational behavior of tripeptide 2 in solution is described. The 1D and 2D 1H-NMR techniques (COSY and ROESY) were used to assign resonances. Observed interproton distance restraints were considered to characterize conformational behavior. Spectral data indicate that tripeptide 2 presents a rigidified structure in DMSO stabilized by H-bond in two gamma-turns. Agreement with experimental data was obtained by averaging the 1H-NMR parameters over several combinations of low-energy conformations.
authors.affiliation: Institut de Chimie Pharmaceutique Albert Lespagnol, Université de Lille, France.
authors.forename: R
authors.initials: R
authors.lastname: Millet
authors.forename: L
authors.initials: L
authors.lastname: Goossens
authors.forename: J F
authors.initials: JF
authors.lastname: Goossens
authors.forename: P
authors.initials: P
authors.lastname: Chavatte
authors.forename: K
authors.initials: K
authors.lastname: Bertrand-Caumont
authors.forename: R
authors.initials: R
authors.lastname: Houssin
authors.forename: J P
authors.initials: JP
authors.lastname: Hénichart
mesh_terms: D000818:Animals; D016466:CHO Cells; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013816:Thermodynamics; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D008024:Ligands; D064729:Neurokinin-1 Receptor Antagonists; D010455:Peptides; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D014364:Tryptophan