title: Conformation-activity relationships in polyketide natural products. Towards the biologically active conformation of epothilone.
abstract: The conformation-activity relationships for the biologically active polyketide, epothilone, have been determined. Computer-based molecular modeling and high field NMR techniques have provided the solution preferences for epothilones and. For the C1-C8 polypropionate region, two conformational families, conformers 1 and 2, have been identified as having significant populations in polar and non-polar solvents. In the C11-C15 region, additional flexibility was observed and two local conformations have been identified as important, conformers 3 and 4. Epothilone analogues with altered conformational profiles have been designed and synthesized. Conformational analysis and the results of biological assays have been correlated to provide increased understanding of the biologically active conformation for the epothilone class of natural product. Conformation-activity relationships have been shown to be an important complement to structure-activity data.
authors.affiliation: Department of Chemistry & Biochemistry and the Walther Cancer Research Center, 251 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN, 46556-5670, USA. taylor.61@nd.edu
authors.forename: Richard E
authors.initials: RE
authors.lastname: Taylor
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Galvin
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Pabba
mesh_terms: D015195:Drug Design; D034261:Epothilones / Q000737:chemistry* / Q000494:pharmacology; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D034261:Epothilones