Abiotic peptides for the encoding of small molecule synthesis

Information storage in DNA forms the fundamental basis of cellular life, but inherent limitations of information stability and density hamper innovative applications such as data storage or drug discovery. Here, we establish abiotic peptides for next-generation information storage and apply them for the encoding of diverse small molecule synthesis. The chemical stability of the peptide-based tag allows the use of palladium-mediated reactions to efficiently synthesize peptide-encoded libraries (PELs) with large chemical diversity and excellent purity. We demonstrate the successful application of PELs in drug discovery by affinity selection yielding small molecules with nanomolar affinity toward their target protein. Collectively, this work establishes abiotic peptides as carriers of information, leveraged herein for the encoding of small molecule synthesis.