title: Solution structure of endothelin B receptor selective antagonist RES-701-1 determined by 1H NMR spectroscopy.
abstract: The three-dimensional structure of the endothelin B receptor (ETB) selective antagonist RES-701-1 has been determined by 1H NMR in deuterated dimethyl sulphoxide. RES-701-1 consists of 16 amino acid residues with a novel internal linkage between the beta-carboxyl group of Asp9 and the alpha-amino group of Gly1. The structural calculations were carried out with the combined use of distance geometry and simulated annealing. The result indicates that RES-701-1 adopts an extraordinary folding; the 'tail' (Trp10-Trp16) passes through the 'ring' region (Gly1-Asp9). Several critical NOEs directly support this extraordinary folding. The folding of RES-701-1 turned out to be the same as that Frèchet et al. calculated for RP 71955 which possesses the same internal linkage as RES-701-1. The obtained structure suggested that the region consisting of Thr6, Ala7, Tyr14 and Tyr15 and/or, the region consisting of Asn2, Tyr14 and Tyr15 are involved in a binding with ETB.
authors.affiliation: Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., Japan.
authors.forename: R
authors.initials: R
authors.lastname: Katahira
authors.forename: K
authors.initials: K
authors.lastname: Shibata
authors.forename: M
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000595:Amino Acid Sequence; D065128:Endothelin Receptor Antagonists; D007189:Indans / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism; D012996:Solutions; D013329:Structure-Activity Relationship
chemical_list: D065128:Endothelin Receptor Antagonists; D007189:Indans; D010456:Peptides, Cyclic; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D012996:Solutions; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-; C087120:RES 701-1