title: Conformation-activity relationships of polyketide natural products.
abstract: Polyketides represent an important class of secondary metabolites that interact with biological targets connected to a variety of disease-associated pathways. Remarkably, nature's assembly lines, polyketide synthases, manufacture these privileged structures through a combinatorial mixture of just a few structural units. This review highlights the role of these structural elements in shaping a polyketide's conformational preferences, the use of computer-based molecular modeling and solution NMR studies in the identification of low-energy conformers, and the importance of conformational analogues in probing the bound conformation. In particular, this review covers several examples wherein conformational analysis complements classic structure-activity relationships in the design of biologically active natural product analogues.
authors.affiliation: University of Notre Dame, Department of Chemistry & Biochemistry, 250 Nieuwland Science Hall, Notre Dame, Indiana, USA. taylor.61@nd.edu.
authors.forename: Erik M
authors.initials: EM
authors.lastname: Larsen
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Wilson
authors.forename: Richard E
authors.initials: RE
authors.lastname: Taylor
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D048630:Polyketide Synthases / Q000378:metabolism*; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D061065:Polyketides; D048630:Polyketide Synthases