化学
蛋白质水解
瓶颈
连接器
生物信息学
合理设计
计算生物学
组合化学
生物化学
遗传学
酶
基因
计算机科学
生物
操作系统
嵌入式系统
作者
Troy A. Bemis,James J. La Clair,Michael D. Burkart
标识
DOI:10.1021/acs.jmedchem.1c00482
摘要
A current bottleneck in the development of proteolysis targeting chimeras (PROTACs) is the empirical nature of linker length structure-activity relationships (SARs). A multidisciplinary approach to alleviate the bottleneck is detailed here. First, we examine four published synthetic approaches that have been developed to increase synthetic throughput. We then discuss advances in structural biology and computational chemistry that have led to successful rational PROTAC design efforts and give promise to de novo linker design in silico. Lastly, we present a model generated from a curated list of linker SARs studies normalized to reflect how linear linker length affects the observed degradation potency (DC50).
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