Research Group of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, Brussels, Belgium.
Research Group of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, Brussels, Belgium.
Trends Pharmacol Sci. 2022 May;43(5):406-423. doi: 10.1016/j.tips.2021.10.011. Epub 2021 Nov 29.
Recent years have seen the rise of allosteric modulation as an innovative approach for drug design and discovery, efforts which culminated in the development of several clinical candidates. Allosteric modulation of many drug targets, including mainly membrane-embedded receptors, have been vastly explored through small molecule screening campaigns, but much less attention has been paid to peptide-based allosteric modulators. However, peptides have a significant impact on the pharmaceutical industry due to the typically higher potency and selectivity for their targets, as compared with small molecule therapeutics. Therefore, peptides represent one of the most promising classes of molecules that can modulate key biological pathways. Here, we report on the allosteric modulation of proteins (ranging from G protein-coupled receptors to specific protein-protein interactions) by peptides for applications in drug discovery.
近年来，变构调节作为一种创新的药物设计和发现方法兴起，这方面的努力最终促成了几种临床候选药物的开发。通过小分子筛选活动，对许多药物靶点（主要是膜嵌入受体）的变构调节进行了广泛的探索，但对基于肽的变构调节剂的关注要少得多。然而，与小分子治疗药物相比，肽类药物通常对其靶点具有更高的效力和选择性，因此对制药行业有重大影响。因此，肽类是能够调节关键生物途径的最有前途的分子类别之一。在这里，我们报告了肽对蛋白质（从 G 蛋白偶联受体到特定的蛋白质-蛋白质相互作用）的变构调节在药物发现中的应用。
