Psoralen as an interstrand DNA crosslinker in the selection of DNA-Encoded dynamic chemical library
Psoralen as an interstrand DNA crosslinker in the selection of DNA-Encoded dynamic chemical library
复制标题
补骨脂素作为 DNA 链间交联剂在 DNA 编码动态化学库选择中的应用
DOI：
10.1016/j.bbrc.2020.04.033
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发表时间：
2020-12-03
影响因子：
3.1
通讯作者：
Li，Xiaoyu
中科院分区：
文献类型：
--
作者：
Zhou，Yu;Peng，Jianzhao;Li，Xiaoyu
DNA编码的化学库（DEL）已成为生物医学研究中发现配体的有力技术。最近，我们已经开发了一种DNA编码的动态库（DEDL）的方法，将动态组合库（DCL）的概念与动态库（DELs）。DEDL已经显示出在针对各种蛋白质靶点的配体发现方面的优异潜力。然而，具有一对非天然的对-芪唑作为链间DNA交联剂的要求限制了DEDL的化学多样性。在此，我们用补骨脂素（PS）包埋对-芪，并测试了补骨脂素作为DEDL选择中的交联剂的可行性。由于pepsilen是可商购的并且不需要任何特殊的交联配偶体，因此现有的DEL可以直接用于产生高多样性的DEDL。这项研究有望大大促进DEDL作为药物发现中的通用工具的发展。
DNA-encoded chemical library (DEL) has emerged as a powerful technology for ligand discovery in biomedical research. Recently, we have developed a DNA-encoded dynamic library (DEDL) approach by incorporating the concept of dynamic combinatorial library (DCL) with DELs. DEDL has shown excellent potential in ligand discovery towards a variety of protein targets. However, the requirement of having a pair of unnaturalp-stilbazoles as the interstrand DNA crosslinker has limited the chemical diversity of DEDLs. Here, we replacedp-stilbazole with psoralen (PS) and tested the feasibility of psoralen as the crosslinker in DEDL selection. Since psoralen is commercially available and does not require any special crosslinking partner, existing DELs may be directly used to create high-diversity DEDLs. This study is expected to greatly facilitate the development of DEDLs as a versatile tool in drug discovery.