Kotnik Miha, Anderluh Petra Stefanic, Prezelj Andrej
Lek Pharmaceuticals d.d., Drug Discovery, Ljubljana, Slovenia.
Curr Pharm Des. 2007;13(22):2283-309. doi: 10.2174/138161207781368828.
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.
对抗生素具有抗性的致病细菌菌株的广泛出现正成为对公众健康的严重威胁。因此，持续开发新型抗菌药物仍然是科学界面临的最大挑战之一，也是临床上未满足的需求。细菌肽聚糖是细胞壁的重要组成部分，其生物合成途径已得到充分研究，似乎是新型抗菌药物有吸引力的酶靶点的丰富来源。因此，我们综述了肽聚糖生物合成的细胞内部分，包括用于形成UDP-GlcNAc的酶GlmS、GlmM、GlmU，随后由MurA-MurF进行的五肽合成，以及其通过MraY和MurG与脂质载体的连接。本文还介绍了天然存在的抑制剂以及肽聚糖合成细胞内部分的低分子量抑制剂的开发情况。
