Pitt Anthony, Nims Zeke
Orbit Discovery Ltd., Oxford, UK.
Methods Mol Biol. 2019;2001:285-298. doi: 10.1007/978-1-4939-9504-2_13.
With an increased interest in the use of peptides as therapeutics comes the need for strategies to allow for the discovery of novel hit candidates, in high-throughput manners, from highly complex peptide libraries. Early development of peptide therapeutics arose from the deployment of natural peptides and subsequent modification to enhance medicinal properties. Here, the implementation of synthetic peptide libraries of low complexity was sufficient, but these low-diversity starting points are an obvious limitation to the discovery of novel peptides. This limitation is compounded by the almost unarguable desire to explore unnatural amino acid chemical space, moving away from the reliance upon natural peptides.
随着人们对将肽用作治疗剂的兴趣日益增加,需要有策略以高通量方式从高度复杂的肽库中发现新的命中候选物。肽治疗剂的早期开发源于天然肽的应用以及随后为增强药用特性而进行的修饰。在此,低复杂度合成肽库的应用就足够了,但这些低多样性的起点显然限制了新型肽的发现。由于几乎无可争议地希望探索非天然氨基酸化学空间,不再依赖天然肽,这一限制更加突出。