One size fits all: The semi-synthesis of new undecaprenol analogues for the study of multiple undecaprenyl-processing enzymes

抗菌素耐药性是对人类健康的主要威胁，因此有必要寻找新的抗菌素靶标。细菌产生几种对其生存至关重要的糖共聚物，包括肽聚糖，这是结构完整性所需的细菌细胞壁的关键成分。细菌细胞壁是许多临床使用的抗生素的靶标，如青霉素和万古霉素。糖共聚物的生物合成涉及几个关键的糖脂中间体，所有这些中间体都通过十一烯醇分子连接到细胞膜上。处理与十一烯醇连接的生物分子的酶是抗生素的热门目标，因为它们是细菌特有的。然而，由于缺乏合适的探针来监测它们的活性，对这些酶的详细研究和高通量筛选可能的抑制剂一直受到限制。了解酶的作用机制是合理设计抑制剂的重要前提。该项目旨在开发新的十一烯醇标记类似物，将用于研究几种新的抗生素靶标，并为高通量筛选潜在的抗生素候选者提供一种方法。

Antibacterial resistance is a major threat to human health and there is a pertinent need for new antimicrobial targets. Bacteria produce several glycopolymers that are vital to their survival, including peptidoglycan, which is a key component of the bacterial cell wall required for structural integrity. The bacterial cell wall is targeted by many clinically used antibiotics, such as penicillin and vancomycin. Glycopolymer biosynthesis involves several key glycolipid intermediates, all of which are linked to the cell membrane by the molecule undecaprenol. The enzymes that process undecaprenol-linked biomolecules are hot antibiotic targets, as they are unique to bacteria. However, detailed studies on these enzymes and the high-throughput screening of possible inhibitors has been limited due to the lack of suitable probes to monitor their activity. An understanding of enzyme mechanism is a vital pre-requisite to the rationale design of inhibitors. This project aims to develop new labelled analogues of undecaprenol, which will be used to study several novel antibiotic targets and provide a method for the high-throughput screening of potential antibiotic candidates.