Department of Chemistry, University of Warwick, Coventry CV47AL, UK.
Trends Biotechnol. 2011 Apr;29(4):167-73. doi: 10.1016/j.tibtech.2010.12.006. Epub 2011 Jan 12.
The development of new antibacterial agents to combat worsening antibiotic resistance is still a priority area in anti-infectives research, but in the post-genomic era it has been more difficult than expected to identify new lead compounds from high-throughput screening, and very challenging to obtain antibacterial activity for lead compounds. Bacterial cell-wall peptidoglycan biosynthesis is a well-established target for antibacterial chemotherapy, and recent developments enable the entire biosynthetic pathway to be reconstituted for detailed biochemical study and high-throughput inhibitor screening. This review article discusses recent developments in the availability of peptidoglycan biosynthetic intermediates, the identification of lead compounds for both the earlier cytoplasmic steps and the later lipid-linked steps, and the application of new methods such as structure-based drug design, phage display and surface science.
开发新的抗菌剂来对抗日益严重的抗生素耐药性仍然是抗感染研究的重点领域，但在后基因组时代，从高通量筛选中识别新的先导化合物比预期的更困难，并且非常具有挑战性获得先导化合物的抗菌活性。细菌细胞壁肽聚糖生物合成是抗菌化疗的一个既定目标，最近的发展使整个生物合成途径得以重建，用于详细的生化研究和高通量抑制剂筛选。本文讨论了肽聚糖生物合成中间体的可用性的最新进展，鉴定了早期细胞质步骤和后期脂联步骤的先导化合物，以及应用新方法，如基于结构的药物设计、噬菌体展示和表面科学。
