title: Development of novel inhibitors targeting intracellular steps of 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 MurA-MurF, 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.
authors: Lek Pharmaceuticals d.d., Drug Discovery, Ljubljana, Slovenia.
authors: Miha
authors: M
authors: Kotnik
authors: Petra Stefanic
authors: PS
authors: Anderluh
authors: Andrej
authors: A
authors: Prezelj
mesh_terms: D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008025:Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D008970:Molecular Weight; D010457:Peptidoglycan / Q000096:biosynthesis*; D014176:Protein Biosynthesis / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010457:Peptidoglycan; D000591:Amino Acid Isomerases; D008025:Ligases