We have developed a peptide synthesis and screening platform for the discovery of peptidic molecules that bind to protein targets of interest. This technique employs the use of digital micromirror devices to direct the maskless synthesis of millions of unique peptides in parallel on a microarray surface. Using a chemical catalog of over 300 amino acid building blocks (natural and non-natural), we can synthesize 18 million unique peptides in less than 48 hours. The method can be applied to synthesize both linear and cyclic peptidic molecules, enabling screens in a diverse chemical space. Here, we will describe the core technology and its application to rapidly and systematically evolve high-affinity, high-specificity binding peptidomimetics to protein targets in a reproducible and digitally controlled process.

High-throughput discovery and parallel optimization of peptide therapeutics

ACS Fall 2021

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