Searching for inhibitors of human H 2 S-synthesizing enzymes by orthogonal methods
FREE RADICAL BIOLOGY AND MEDICINE(2018)
摘要
Hydrogen sulfide (H 2 S), a key signalling molecule in human patho-physiology, is produced by the human enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MST). Increasing evidence indicates a correlation between increased H 2 S production and human diseases, such as several cancer types and amyotrophic lateral sclerosis. Identifying selective and potent inhibitors may be beneficial for future therapeutic strategies. Here, recombinant CBS, CSE and MST were expressed and purified, and 31 pyridine derivatives were synthesized and screened for their ability to bind and inhibit these enzymes. Using a combination of orthogonal methodologies, such as differential scanning fluorimetry (DSF), surface plasmon resonance (SPR), circular dichroism (CD) spectropolarimetry, and activity assays based on fluorimetric and colorimetric H 2 S detection, two compounds sharing the same molecular scaffold showed a weak inhibition of both CBS and CSE. The present work, while presenting a robust methodological platform for screening putative inhibitors of the three human H 2 S-synthesizing enzymes, highlights the importance of employing complementary methodologies to identify possible false positives in compound screening campaigns.
更多查看译文
关键词
enzymes,inhibitors,s-synthesizing
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要