Institute for Systems Biology, Seattle, WA, USA.
Indi Molecular, Inc., Culver City, CA, USA.
Methods Mol Biol. 2022;2371:177-191. doi: 10.1007/978-1-0716-1689-5_10.
The protein catalyzed capture agent (PCC) method is a powerful combinatorial screening strategy for discovering synthetic macrocyclic peptide ligands, called PCCs, to designated protein epitopes. The foundational concept of the PCC method is the use of in situ click chemistry to survey large combinatorial libraries of peptides for ligands to designated biological targets. State-of-the-art PCC screens integrate synthetic libraries of constrained macrocyclic peptides with epitope-specific targeting strategies to identify high-affinity (<100 nM) binders de novo. Automated instrumentation can accelerate PCC discovery to a rapid 2-week timeframe. Here, we describe methods to perform combinatorial screens that yield epitope-targeted PCCs.
蛋白催化捕获试剂（PCC）方法是一种强大的组合筛选策略，用于发现针对指定蛋白表位的合成大环肽配体，称为 PCC。PCC 方法的基础概念是使用原位点击化学来筛选针对指定生物靶标的肽的大型组合文库，以寻找配体。最先进的 PCC 筛选将约束性大环肽的合成文库与表位特异性靶向策略相结合，以从头鉴定高亲和力（<100 nM）的配体。自动化仪器可以将 PCC 的发现速度加快到 2 周的快速时间框架内。在这里，我们描述了进行组合筛选的方法，这些筛选可以产生针对表位的 PCC。
