期刊
ORGANIC & BIOMOLECULAR CHEMISTRY
卷 20, 期 7, 页码 1444-1452出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1ob02080c
关键词
-
资金
- Department of Science and Technology, Ministry of Science and Technology, India [SB/S1/OC-94/2013]
- Department of Biotechnology, Government of India [BT/PR40990/MED/29/1540/2020]
- Indian Institute of Technology Kharagpur
By conducting experiments and in vitro studies, we have successfully demonstrated the interaction between thioacetazone and multiple enzymes, further confirming these enzymes as targets for thioacetazone. This has important implications for the development of new thioacetazone analogues with fewer side effects.
Thioacetazone (TAC) used to be a highly affordable, bacteriostatic anti-TB drug but its use has now been restricted, owing to severe side-effects and the frequent appearance of the TAC resistant M. tuberculosis strains. In order to develop new TAC analogues with fewer side-effects, its target enzymes need to be firmly established. It is now hypothesized that TAC, after being activated by a monooxygenase EthA, binds to the dehydratase complex HadAB that finally leads to a covalent modification of HadA, the main partner involved in dehydration. Another dehydratase enzyme, namely HadC in the HadBC complex, is also thought to be a possible target for TAC, for which definitive evidence is lacking. Herein, using a recently exploited azido naphthalimide template attached to thioacetazone and adopting a photo-affinity based labelling technique, coupled with electrophoresis and in-gel visualization, we have successfully demonstrated the involvement of these enzymes including HadBC along with a possible participation of an alternate mycobacterial monooxygenase MymA. In silico studies also revealed strong interactions between the TAC-probe and the concerned enzymes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据