Definition of new pharmacophores for nonpeptide antagonists of human urotensin-II. Comparison with the 3D-structure of human urotensin-II and URP.
Starting from nonpeptide agonists and antagonists of human urotensin-II (hU-II), several pharmacophores were designed and compared to the structure of hU-II. NMR and dynamic studies were realized on hU-II and urotensin-II-related peptide to check the conformation flexibilities of these peptides and the relationships between their potential 3D structures and the pharmacophores. In parallel, a virtual screening was carried out, leading to the discovery of six new derivatives with micromolar affinities. This last result shows the interest of these pharmacophores for the discovery of new ligands.
Lescot
Elodie
E
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Université de Caen, U.F.R. des Sciences Pharmaceutiques, 5 rue Vaubénard, 14032 Caen Cedex, France.
Sopkova-de Oliveira Santos
Jana
J
Dubessy
Christophe
C
Oulyadi
Hassan
H
Lesnard
Aurélien
A
Vaudry
Hubert
H
Bureau
Ronan
R
Rault
Sylvain
S
D000577:Amides / Q000737:chemistry; D019295:Computational Biology; D006801:Humans; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry; D011522:Protons; D014579:Urotensins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism
D000577:Amides; D010455:Peptides; D011522:Protons; D014579:Urotensins; C029677:urotensin II