Efficient drug discovery by rational lead hybridization based on crystallographic overlay
Efficient drug discovery by rational lead hybridization based on crystallographic overlay
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通过基于晶体学叠加的合理先导杂交实现高效药物发现
DOI：
10.1016/j.drudis.2018.11.021
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通讯作者：
Peng Zhan
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作者：
Shuo Zhang;Jian Zhang;Ping Gao;Lin Sun;Yuning Song;Dongwei Kang;Xinyong Liu;Peng Zhan
基于晶体学重叠的合理的先导杂交是一种有效的药物发现方法。越来越高通量的蛋白质与配体的X射线共晶体学为基于晶体学重叠的先导杂交提供了良好的基础。耐受的溶剂-特定药物靶点的暴露区域为基于晶体学覆盖的分子杂交提供了广阔的空间。较大杂交分子的物理化学性质需要在这篇综述中，我们提供了一个概述最近的应用结晶覆盖为基础的分子结构杂交的先导化合物作为一个合理的策略，有效的药物发现，与选定的例子，并简要讨论了它的优势相比，其他配体为基础的方法。
HighlightsRational lead hybridization based on crystallographic overlays is an efficient drug discovery approach.Increasingly high-throughput X-ray co-crystallography of proteins with ligands provides an excellent basis for lead hybridization based on crystallographic overlays.The tolerated solvent-exposed regions in the specific drug target provide a broad space for molecular hybridization based on crystallographic overlays.The physicochemical properties of larger hybrid molecules need to be addressed.In this review, we provide an overview of recent applications of crystallographic overlay-based molecular structure hybridization of lead compounds as a rational strategy for efficient drug discovery, with selected examples, and briefly discuss its advantages compared with other ligand-based methodologies.