Larsen Erik M, Wilson Matthew R, Taylor Richard E
University of Notre Dame, Department of Chemistry & Biochemistry, 250 Nieuwland Science Hall, Notre Dame, Indiana, USA.
Nat Prod Rep. 2015 Aug;32(8):1183-206. doi: 10.1039/c5np00014a.
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.
聚酮化合物是一类重要的次生代谢产物，它们与连接到各种疾病相关途径的生物靶点相互作用。值得注意的是，自然界的装配线——聚酮合酶，通过仅几种结构单元的组合混合物来制造这些特殊结构。本综述强调了这些结构元件在塑造聚酮化合物构象偏好方面的作用、基于计算机的分子建模和溶液核磁共振研究在鉴定低能量构象体中的应用，以及构象类似物在探测结合构象方面的重要性。特别是，本综述涵盖了几个例子，其中构象分析在生物活性天然产物类似物的设计中补充了经典的构效关系。
