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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Development of Novel Inhibitors Targeting Intracellular Steps of Peptidoglycan Biosynthesis

Author(s): Miha Kotnik, Petra Stefanic Anderluh and Andrej Prezelj

Volume 13, Issue 22, 2007

Page: [2283 - 2309] Pages: 27

DOI: 10.2174/138161207781368828

Price: $65

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Abstract

The widespread emergence of pathogenic bacterial strains with resistance to antibiotics is becoming a serious threat to public health. Continuous development of novel antibacterials therefore remains one of the biggest challenges to science and unmet needs in the clinics. The biosynthetic pathway of bacterial peptidoglycan, an essential building block of cell walls, has been well studied and appears to be a rich source of attractive enzyme targets for new antibacterials. We have therefore reviewed the intracellular part of peptidoglycan biosynthesis, including the enzymes GlmS, GlmM, GlmU for formation of UDP-GlcNAc, subsequent pentapeptide synthesis by MurAMurF, and its connection to lipid carrier by MraY and MurG. Naturally occurring inhibitors and the development of low-molecular weight inhibitors of the intracellular part of peptidoglycan synthesis are presented.

Keywords: Peptidoglycan, Mur ligases, inhibitors of intracellular peptidoglycan biosynthesis


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