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
Current Pharmaceutical Design
Title: Development of Novel Inhibitors Targeting Intracellular Steps of Peptidoglycan Biosynthesis
Volume: 13 Issue: 22
Author(s): Miha Kotnik, Petra Stefanic Anderluh and Andrej Prezelj
Affiliation:
Keywords: Peptidoglycan, Mur ligases, inhibitors of intracellular peptidoglycan biosynthesis
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.
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Cite this article as:
Miha Kotnik , Petra Stefanic Anderluh and Andrej Prezelj , Development of Novel Inhibitors Targeting Intracellular Steps of Peptidoglycan Biosynthesis, Current Pharmaceutical Design 2007; 13 (22) . https://dx.doi.org/10.2174/138161207781368828
DOI https://dx.doi.org/10.2174/138161207781368828 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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