Department of Science, Systems and Models, Roskilde University, Universitetsvej 1, Building 18.1, DK-4000 Roskilde, Denmark.
Chem Biol Drug Des. 2011 Feb;77(2):107-16. doi: 10.1111/j.1747-0285.2010.01067.x.
The field of drug discovery and development has seen tremendous activity over the past decade to better tackle the increasing occurrence of drug-resistant bacterial infections and to alleviate some of the pressure we put on the last-resort drugs on the market. One of the new and promising drug candidates is derived from naturally occurring antimicrobial peptides. However, despite promising results in early-stage clinical trials, these molecules have faced some difficulties securing FDA approval, which can be linked to their poor metabolic stability. Hence, mimetics of these antimicrobial peptides have been suggested as new templates for antibacterial compound design, because these mimetics are resistant against degradation by proteases. This review will discuss the structural features of two different types of mimetics, β-peptides and α-peptoids, in relation to their antibacterial activity and conclude on their potential as new candidates for bacterial intervention.
在过去的十年中,药物发现和开发领域非常活跃,旨在更好地解决日益增加的耐药性细菌感染问题,并减轻我们对市场上最后手段药物的一些压力。一种新的有前途的药物候选物来自天然存在的抗菌肽。然而,尽管在早期临床试验中取得了有希望的结果,但这些分子在获得 FDA 批准方面遇到了一些困难,这可能与其代谢稳定性差有关。因此,这些抗菌肽的类似物被提议作为抗菌化合物设计的新模板,因为这些类似物能够抵抗蛋白酶的降解。这篇综述将讨论两种不同类型的类似物,β-肽和α-肽,与它们的抗菌活性相关的结构特征,并对它们作为细菌干预的新候选物的潜力进行总结。