靶向细菌RNA聚合酶组装的新型合成分子。
Novel synthetic molecules targeting the bacterial RNA polymerase assembly.
作者信息
André Estelle, Bastide Lionel, Michaux-Charachon Sylvie, Gouby Anne, Villain-Guillot Philippe, Latouche Jaqueline, Bouchet Aurélie, Gualtiéri Maxime, Leonetti Jean-Paul
机构信息
CPBS CNRS UMR 5160, Faculté de Pharmacie 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier Cedex 5, France.
出版信息
J Antimicrob Chemother. 2006 Feb;57(2):245-51. doi: 10.1093/jac/dki426. Epub 2005 Dec 22.
OBJECTIVES
Despite extensive functional screening of the bacterial RNA polymerase (RNAP) over the past years, very few novel inhibitors have been reported. We have, therefore, decided to screen with a radically different, non-enzymic, protein-protein interaction assay. Our target is the highly conserved RNAP-sigma interaction that is essential for transcription.
METHODS
Small molecule inhibitors of the RNAP-sigma interaction were tested for their activity on transcription and on bacteria.
RESULTS
These compounds have antibacterial activity against Gram-positive bacteria including multiresistant clinical isolates.
CONCLUSIONS
This is, to our knowledge, the first example of a small molecule inhibitor of this interaction.
目的
尽管在过去几年中对细菌RNA聚合酶（RNAP）进行了广泛的功能筛选，但报道的新型抑制剂却非常少。因此，我们决定采用一种截然不同的非酶促蛋白质-蛋白质相互作用检测方法进行筛选。我们的目标是高度保守的RNAP-σ相互作用，它对转录至关重要。
方法
测试了RNAP-σ相互作用的小分子抑制剂对转录和细菌的活性。
结果
这些化合物对革兰氏阳性菌具有抗菌活性，包括多重耐药临床分离株。
结论
据我们所知，这是这种相互作用的小分子抑制剂的首个实例。
Zotero 插件