Novel inhibitors against the bacterial signal peptidase I.
- Author:
Guo-Jian LIAO
1
;
Ying HE
;
Jian-Ping XIE
Author Information
1. Institute of Modern Biopharmaceuticals, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Anti-Bacterial Agents;
pharmacology;
Bacteria;
drug effects;
Escherichia coli;
drug effects;
Membrane Proteins;
antagonists & inhibitors;
metabolism;
Oligopeptides;
chemistry;
pharmacology;
Serine Endopeptidases;
metabolism;
Serine Proteinase Inhibitors;
chemistry;
pharmacology;
Structure-Activity Relationship;
beta-Lactams;
antagonists & inhibitors
- From:
Acta Pharmaceutica Sinica
2012;47(12):1561-1566
- CountryChina
- Language:Chinese
-
Abstract:
New antibiotics with novel modes of action and structures are urgently needed to combat the emergence of multidrug-resistant bacteria. Bacterial signal peptidase I (SPase I) is an indispensable enzyme responsible for cleaving the signal peptide of preprotein to release the matured proteins. Increasing evidence suggests that SPase I plays a crucial role in bacterial pathogenesis by regulating the excretion of a variety of virulent factors, maturation of quorum sensing factor and the intrinsic resistance against beta-lactams. Recently, breakthrough has been achieved in the understanding of three-dimensional structure of SPase I as well as the mechanism of enzyme-inhibitors interaction. Three families of inhibitors are identified, i.e. signal peptide derivatives, beta-lactams and arylomycins. In this article, we summarize the recent advance in the study of structure, activity and structure-activity relationship of SPase I inhibitors.
