Bacterial protease inhibitors

被引:143
|
作者
Supuran, CT
Scozzafava, A
Clare, BW
机构
[1] Univ Florence, Dipartimento Chim, Lab Chim Inorgan & Bioinorgan, I-50019 Florence, Italy
[2] Univ Western Australia, Dept Chem, Nedlands, WA 6009, Australia
关键词
AAA protease; antibiotics; anthrax lethal factor; botulinum neurotoxins; Clostridium collagenase; cysteine protease; degP; metalloprotease; serine protease; sortase; tetanus neurotoxin;
D O I
10.1002/med.10007
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Serine-, cysteine and metalloproteases are widely spread in many pathogenic bacteria, where they play critical functions related to colonization and evasion of host immune defenses, acquisition of nutrients for growth and proliferation, facilitation of dissemination, or tissue damage during infection. Since all the antibiotics used clinically at the moment share a common mechanism of action, acting as inhibitors of the bacterial cell wall biosynthesis or affecting protein synthesis on ribosomes, resistance to these pharmacologoical agents represents a serious medical problem, which might be resolved by using new generation of antibiotics, possessing a different mechanism of action. Bacterial protease inhibitors constitute an interesting such possibility, due to the fact that many specific as well as ubiquitous proteases have recently been characterized in some detail in both gram-positive as well as gram-negative pathogens. Few Potent, specific inhibitors for such bacterial proteases have been reported at this moment except for some signal peptidase, clostripain, Clostridium histolyticum collagenase. botulinum neurotoxin, and tetanus neurotoxin inhibitors, No inhibitors of the critically important and ubiquitous AAA proteases. degP or sortase have been reported, although such compounds would presumably constitute a new class of highly effective antibiotics. This review presents the state of the art in the design of such enzyme inhibitors with potential therapeutic applications, as well as recent advances in the use of some of these proteases in therapy. (C) 2002 Wiley Periodicals Inc.
引用
收藏
页码:329 / 372
页数:44
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