Isothermal titration calorimetry: controlling binding forces in lead optimization.
Isothermal titration calorimetry: controlling binding forces in lead optimization.
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DOI：
10.1016/j.ddtec.2004.11.016
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发表时间：
2004-12-01
期刊：
影响因子：
--
通讯作者：
Freire, Ernesto
中科院分区：
文献类型：
--
作者：
Freire, Ernesto
人类基因组的完成为药物开发鉴定了大量新靶点。这些靶标中的许多属于具有同源结构和相似活性位点的蛋白质家族。针对这些目标，成功的药物必须表现出高亲和力和高选择性，这些目标一直难以实现，并且强调需要更好的优化策略。这些策略需要控制使对预期靶标的亲和力最大化并使对其他蛋白质的亲和力最小化的力。由于等温滴定量热法（ITC）是唯一的实验技术，提供了一个分区的结合能到其热力学和熵的分量，它正在迅速成为一个关键技术，在铅优化。
The completion of the human genome has resulted in the identification of large numbers of novel targets for drug development. Many of these targets belong to protein families with homologous structures and similar active sites. Against these targets, successful drugs must display high affinity and high selectivity, goals that have been difficult to accomplish and that emphasize the need for better optimization strategies. Those strategies require control over the forces that maximize affinity towards the intended target and minimize affinity towards other proteins. Because isothermal titration calorimetry (ITC) is the only experimental technique that provides a partition of the binding energy into its enthalpic and entropic components, it is rapidly becoming a key technology in lead optimization.: