Abstract
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 (<100nM) 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.
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