上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

SUMO特异性蛋白酶1的小分子抑制剂JK043的合成与生物学活性的初步研究

陈颖毅1，孙金铃2，李帅1，张健1，吴英理1   

  1. 上海交通大学 1.基础医学院病理生理学教研室 细胞分化与凋亡教育部重点实验室， 上海 200025； 2.医学院附属国际和平妇幼保健院超声科， 上海 200030
  • 出版日期:2016-02-28 发布日期:2016-03-29
  • 通讯作者: 吴英理, 电子信箱: wuyingli@shsmu.edu.cn。
  • 作者简介:陈颖毅（1984—），男，硕士生; 电子信箱: chen_yy@sjtu.edu.cn。

Preliminary study on the synthesis and biological activity of small molecule #br# inhibitor JK043 of SUMO-specific protease 1

CHEN Ying-yi1, SUN Jin-ling2, LI Shuai1, ZHANG Jian1, WU Ying-li1   

  1. 1.Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Basic Medicine Faculty ofShanghai Jiao Tong University, Shanghai 200025; 2.Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030
  • Online:2016-02-28 Published:2016-03-29

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摘要：

目的 通过虚拟筛选的方法发现SUMO特异性蛋白酶1（SENP1）新的小分子抑制剂，并对其生物学活性进行体外验证。方法 通过对小分子数据库虚拟筛选，得到可能的SENP1小分子抑制剂。化学合成筛选得到的JK043，经SENP1的体外测试体系验证该小分子的抑制活性，计算IC50。构建对接模型，观察JK043与SENP1的作用模式。结果 通过体外活性测试发现，化学合成的JK043能够抑制SENP1的活性，IC50值为1.339 μmol/L。通过对接模型发现，JK043与SENP1蛋白的465W、468D、529H、597Q存在相互作用关系。结论 发现并合成JK043，其对SENP1有一定的体外抑制活性。

关键词: SUMO特异性蛋白酶1, 抑制剂, 虚拟筛选, 化学合成

Abstract:

Objective To identify novel small molecule inhibitors of SENP1 by virtual screening and evaluate the biological activity in vitro. Methods The possible small molecule inhibitors of SENP1 were selected from the small molecule database by virtual screening. Screened JK043 were chemically synthesized and the inhibitory effect of JK043 on the activity of SENP1 was evaluated by the in vitro test system of SENP1. IC50 was calculated. The action mode between JK043 and SENP1 was then observed through the docking model. Results The activity test in vitro showed that chemically synthesized JK043 could inhibit the activity of SENP1 and the valued of IC50 was 1.339 μmol/L. The docking model indicated that JK043 interacted with 465W, 468D, 529H, and 597Q of SENP1 protein. Conclusion JK043 has been identified and synthesized, which can inhibit the activity of SENP1 in vitro to a certain extent.

Key words: SENP1, inhibitor, virtual screening, chemical synthesis