title: A note on the conformational flexibility of the antiestrogenic drug tamoxifen: preferred conformations in the free state and bound to the protein calmodulin.
abstract: The conformational properties of the antiestrogenic drug tamoxifen, a triphenylbut-1-ene derivative, have been studied using molecular mechanics. Four distinct conformers have been identified, and the energy barriers between them have been established. The orientation of the ethyl group substituent has been examined in particular, since the lowest-energy conformers have this group orientated 180 degrees away from its position in the crystal structures of tamoxifen and its derivatives. These differences have implications for the interactions of tamoxifen with the calcium-binding protein calmodulin; relevant results from a molecular-modelling study of this protein-drug complex are presented.
authors.affiliation: Cancer Research Campaign Biomolecular Structure Unit, Institute of Cancer Research, Sutton, Surrey, England.
authors.forename: K J
authors.initials: KJ
authors.lastname: Edwards
authors.forename: C A
authors.initials: CA
authors.lastname: Laughton
authors.forename: S
authors.initials: S
authors.lastname: Neidle
mesh_terms: D002147:Calmodulin / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D013629:Tamoxifen / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D002147:Calmodulin; D013629:Tamoxifen