title: The solution structure of a cyclic endothelin antagonist, BQ-123, based on 1H-1H and 13C-1H three bond coupling constants.
abstract: A cyclic pentapeptide endothelin antagonist, cyclo(dTrp-dAsp-Pro-dVal-Leu), recently reported (K. Ishikawa et al., 13th Am. Pept. Symp., Cambridge MA, 1991) has been studied by NMR spectroscopy and molecular modeling. A stable structure has been determined without the use of nuclear Overhauser effects and is based primarily on homonuclear and heteronuclear three bond coupling constants. The 13C-edited TOCSY experiment is demonstrated at natural abundance and approximately 30 mM peptide concentrations. Three bond 13C-1H coupling constants obtained by this method are shown to reduce the ambiguity in phi angle determination which exists when only interproton coupling constants are used. Three out of four phi angles were determined uniquely by this method and the fourth was reduced to two possible values. The proline phi angle was determined to be -78 degrees based on the 3JH alpha, H beta and 3JH alpha, H beta coupling constants. Comparison of amide proton temperature dependence, chemical shifts and vicinal proton coupling constants in a 20% acetonitrile/80% water solvent mixture and in (CD3)2SO indicates that the structure is similar in both solvents.
authors.affiliation: Chemistry Department, Parke-Davis Pharmaceutical Research Division, Warner Lambert Company, Ann Arbor, MI 48105.
authors.forename: M D
authors.initials: MD
authors.lastname: Reily
authors.forename: V
authors.initials: V
authors.lastname: Thanabal
authors.forename: D O
authors.initials: DO
authors.lastname: Omecinsky
authors.forename: J B
authors.initials: JB
authors.lastname: Dunbar
authors.forename: A M
authors.initials: AM
authors.lastname: Doherty
authors.forename: P L
authors.initials: PL
authors.lastname: DePue
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D016232:Endothelins / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D012996:Solutions
chemical_list: D016232:Endothelins; D010456:Peptides, Cyclic; D012996:Solutions; C072247:cyclo(Trp-Asp-Pro-Val-Leu)