Galley Nicola F, O'Reilly Amy M, Roper David I
School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
Bioorg Chem. 2014 Aug;55(100):16-26. doi: 10.1016/j.bioorg.2014.05.007. Epub 2014 May 21.
The lack of novel antimicrobial drugs under development coupled with the increasing occurrence of resistance to existing antibiotics by community and hospital acquired infections is of grave concern. The targeting of biosynthesis of the peptidoglycan component of the bacterial cell wall has proven to be clinically valuable but relatively little therapeutic development has been directed towards the transglycosylase step of this process. Advances towards the isolation of new antimicrobials that target transglycosylase activity will rely on the development of the enzymological tools required to identify and characterise novel inhibitors of these enzymes. Therefore, in this article, we review the assay methods developed for transglycosylases and review recent novel chemical inhibitors discovered in relation to both the lipidic substrates and natural product inhibitors of the transglycosylase step.
正在研发的新型抗菌药物的匮乏，再加上社区获得性感染和医院获得性感染对现有抗生素的耐药性日益增加，令人深感担忧。事实证明，针对细菌细胞壁肽聚糖成分的生物合成进行靶向治疗具有临床价值，但针对该过程转糖基化步骤的治疗开发相对较少。分离靶向转糖基化酶活性的新型抗菌药物的进展将依赖于开发用于鉴定和表征这些酶的新型抑制剂所需的酶学工具。因此，在本文中，我们综述了为转糖基化酶开发的检测方法，并回顾了最近发现的与转糖基化步骤的脂质底物和天然产物抑制剂相关的新型化学抑制剂。
