title: Active conformation of a tumor promoter, teleocidin. A molecular dynamics study.
abstract: Telecidins are potent tumor promoters, having a nine-membered lactam structure. Teleocidins and their small-molecular-sized active congeners (indolactams) are known to exist in an equilibrium between at least two conformational states, the twist and the sofa form. Molecular dynamics (MD) calculations were performed on four indolactams, in order to examine the relationships between preferred ring conformations and the biological activities. It was shown that the tumor-promoting activities are closely related with the existence ratio of the sofa form among 10 possible conformations. This implies that the sofa form is the active ring conformation, which is compatible with the previous result obtained independently from the superposition of teleocidin and phorbol ester. The predicted ratios of conformers for each indolactam were in good agreement with those observed by NMR spectral analysis. The high-temperature MD method proved to be very useful for predicting the preferred structures of these cyclic compounds, in which the overall stabilities are strongly influenced by the conformations of substituent groups on the ring.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Tokyo.
authors.forename: T
authors.initials: T
authors.lastname: Kawai
authors.forename: T
authors.initials: T
authors.lastname: Ichinose
authors.forename: Y
authors.initials: Y
authors.lastname: Endo
authors.forename: K
authors.initials: K
authors.lastname: Shudo
authors.forename: A
authors.initials: A
authors.lastname: Itai
mesh_terms: D002273:Carcinogens / Q000737:chemistry*; D003460:Crystallization; D008235:Lyngbya Toxins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013816:Thermodynamics
chemical_list: D002273:Carcinogens; D008235:Lyngbya Toxins; C022176:teleocidins