Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Chem Soc Rev. 2021 Apr 7;50(7):4245-4258. doi: 10.1039/d0cs01386b. Epub 2021 Feb 26.
The growing antimicrobial resistance crisis necessitates the discovery and development of novel classes of antibiotics if a 'postantibiotic era' is to be avoided. Ribosomally synthesised and post-translationally modified peptides, or RiPPs, are becoming increasingly recognised as a potential source of antimicrobial drugs. This is due to a combination of their potent antimicrobial activity and their high stability relative to unmodified linear peptides. However, as peptide drugs, their clinical development is often perturbed by issues such as low solubility and poor bioavailability. Chemical synthesis has the potential to overcome some of these challenges. Furthermore, the structural complexity of RiPPs makes them interesting synthetic targets in their own right, with the total synthesis of some structural classes having only been recently realised. This review focusses on the use of RiPPs as antimicrobial agents and will highlight various strategies that have been employed to chemically synthesise three major classes of RiPPs: lasso peptides, cyclotides, and lanthipeptides.
日益严重的抗菌药物耐药性危机要求我们必须发现和开发新型抗生素，否则人类将可能进入“后抗生素时代”。核糖体合成后经翻译修饰的肽类（RiPPs），由于其强大的抗菌活性和相对线性未修饰肽类更高的稳定性，正逐渐被认为是一种有潜力的抗菌药物来源。然而，作为肽类药物，其临床开发常常受到一些问题的困扰，如低溶解度和差的生物利用度。化学合成具有克服这些挑战的潜力。此外，RiPPs 的结构复杂性使其本身成为有趣的合成目标，某些结构类别的全合成最近才刚刚实现。本文综述了 RiPPs 作为抗菌剂的应用，并重点介绍了用于化学合成三大类 RiPP 的各种策略：套索肽、环肽和硫肽。
