紫杉醇生物活性构象研究的最新进展。
Recent advances in the study of the bioactive conformation of taxol.
作者信息
Sun Liang, Simmerling Carlos, Ojima Iwao
机构信息
Department of Chemistry and Institute of Chemical Biology & Drug Discovery, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA.
出版信息
ChemMedChem. 2009 May;4(5):719-31. doi: 10.1002/cmdc.200900044.
Abstract
Paclitaxel is one of the most important chemotherapeutic drugs in the fight against cancer. This minireview covers the recent advances in the study of the bioactive conformation of paclitaxel in tubulin/microtubules. The tubulin-bound structure of paclitaxel has been studied by means of photoaffinity labeling, cryo-electron microscopy, solid-state NMR, molecular modeling, MD simulations and the synthesis of conformationally restrained analogues and paclitaxel mimics. The bioactive conformation of paclitaxel is important since it could provide critical information that would allow the design of novel analogues with simpler structures and/or increased potency against cancer.
摘要
紫杉醇是抗癌斗争中最重要的化疗药物之一。这篇综述涵盖了紫杉醇在微管蛋白/微管中生物活性构象研究的最新进展。已通过光亲和标记、冷冻电子显微镜、固态核磁共振、分子建模、分子动力学模拟以及构象受限类似物和紫杉醇模拟物的合成来研究紫杉醇与微管蛋白结合的结构。紫杉醇的生物活性构象很重要，因为它可以提供关键信息，从而有助于设计结构更简单和/或抗癌效力更高的新型类似物。
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