Developments of bioorthogonal handle-containing photo-crosslinkers for photoaffinity labeling,RSC Medicinal Chemistry

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Developments of bioorthogonal handle-containing photo-crosslinkers for photoaffinity labeling
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2017-06-14 00:00:00 , DOI: 10.1039/c7md00217c
Haijun Guo _{1,

2,

3,

4} , Zhengqiu Li _{1,

2,

3,

4}

Affiliation

Photoaffinity labeling (PAL) has been widely applied in various research areas such as medicinal chemistry, chemical biology and structural biology, owing to its capability of investigating non-covalent ligand–protein interactions under native environments and elucidating protein structures, functions etc. One important application of this technique is to use affinity-based proteome profiling (AfBP) coupled with bioimaging for profiling drug–target interactions in situ. In order to accurately report drug–target interactions via these approaches, several considerations as follows need to be made: (1) maximally retaining bioactivities of photoprobes upon functionalization with a photoreactive group and a reporter tag from a parental compound; (2) performing proteome profiling and imaging in situ simultaneously, to monitor drug–target interactions in different manners; and (3) developing excellent photo-crosslinkers capable of photo-crosslinking and fluorescence turn-on at the same time. With these considerations in mind, we have developed three versions of “minimalist” bioorthogonal handle-containing photo-crosslinkers (L3–L6) during the years and successfully applied them in all kinds of small bioactive molecules for protein labeling and cellular imaging studies. In this mini-review, the features and functions of these linkers are specifically highlighted and summarized.

中文翻译：

用于光亲和标记的含生物正交柄的光交联剂的开发

光亲和标记（PAL）已经在各个研究领域，如药物化学，化学生物学和结构生物学，由于其在调查本地环境非共价配体-蛋白质相互作用和阐明蛋白质结构的能力得到了广泛的应用，功能等的一个重要该技术的应用是将基于亲和力的蛋白质组图谱（A f BP）与生物成像结合使用，以原位分析药物-靶标相互作用。为了准确地报告药物-靶相互作用通过这些方法中，需要考虑以下几个方面：（1）在用来自母体化合物的光反应性基团和报道分子标记官能化后，最大程度地保持光探针的生物活性；（2）进行蛋白质组分析和原位成像同时，以不同的方式监测药物与靶标的相互作用；（3）开发出能够同时进行光交联和开启荧光的优异的光交联剂。考虑到这些考虑因素，这些年来，我们开发了三种版本的“极简”生物正交柄含光交联剂（L3-L6），并将其成功应用于各种小的生物活性分子中，以进行蛋白质标记和细胞成像研究。在此迷你审查中，将特别强调和概述这些链接器的特性和功能。

更新日期：2017-08-16

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