Current advances of carbene-mediated photoaffinity labeling in medicinal chemistry.
Current advances of carbene-mediated photoaffinity labeling in medicinal chemistry.
复制标题
DOI：
10.1039/c8ra03538e
复制
发表时间：
2018-08-14
期刊：
影响因子：
3.9
通讯作者：
Yang, Song
中科院分区：
文献类型：
--
作者：
Ge, Sha-Sha;Chen, Biao;Wu, Yuan-Yuan;Long, Qing-Su;Zhao, Yong-Liang;Wang, Pei-Yi;Yang, Song
光亲和标记(PAL)与化学探针相结合，在紫外光照射下与靶分子共价结合，在药物发现中识别新的药物靶点和结合部位显示出很大的应用前景。特别是，卡宾介导的光亲和标记法(CmPAL)由于其良好的光标记效率、最小的空间位阻干扰和较长的激发波长而被广泛应用于药物靶标识别。具体地说，二氮杂环化合物是卡宾的前体之一，与重氮化合物相比具有更高的卡宾产量和更大的化学稳定性，在各种生物体系中已被证明是有价值的光敏试剂。本文综述了cmPAL在药物化学中的最新进展，重点介绍了cmPAL在识别小分子-蛋白质、大分子-蛋白质相互作用和配基门控离子通道方面的结构和应用，以及近几十年来开发的卡宾前体生物探针在发现靶点和抑制剂方面的进展。光亲和标记(PAL)与化学探针相结合，在紫外光照射下与靶分子共价结合，在药物发现中识别新的药物靶点和结合部位显示出很大的应用前景。
Photoaffinity labeling (PAL) in combination with a chemical probe to covalently bind its target upon UV irradiation has demonstrated considerable promise in drug discovery for identifying new drug targets and binding sites. In particular, carbene-mediated photoaffinity labeling (cmPAL) has been widely used in drug target identification owing to its excellent photolabeling efficiency, minimal steric interference and longer excitation wavelength. Specifically, diazirines, which are among the precursors of carbenes and have higher carbene yields and greater chemical stability than diazo compounds, have proved to be valuable photolabile reagents in a diverse range of biological systems. This review highlights current advances of cmPAL in medicinal chemistry, with a focus on structures and applications for identifying small molecule–protein and macromolecule–protein interactions and ligand-gated ion channels, coupled with advances in the discovery of targets and inhibitors using carbene precursor-based biological probes developed in recent decades. Photoaffinity labeling (PAL) in combination with a chemical probe to covalently bind its target upon UV irradiation has demonstrated considerable promise in drug discovery for identifying new drug targets and binding sites.
登录
查看更多内容
影响因子：
8
作者：
Craig, PO;Ureta, DB;Delfino, JM
通讯作者：
Delfino, JM
影响因子：
2.7
作者：
Bongo, Nlandu B.;Tomohiro, Takenori;Hatanaka, Yasumaru
通讯作者：
Hatanaka, Yasumaru
影响因子：
15
作者：
Chan, EWS;Chattopadhaya, S;Yao, SQ
通讯作者：
Yao, SQ
影响因子：
48
作者：
Barglow, Katherine T.;Cravatt, Benjamin F.
通讯作者：
Cravatt, Benjamin F.
影响因子：
3.6
作者：
Alcaraz, ML;Peng, L;Goeldner, M
通讯作者：
Goeldner, M