Abiotic peptides as carriers of information for the encoding of small-molecule library synthesis.

ABSTRACT: Encoding small-molecule information in DNA has been leveraged to accelerate the discovery of ligands for therapeutic targets such as proteins. However, oligonucleotide-based encoding is hampered by inherent limitations of information stability and density. In this study, 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 broad chemical diversity and high purity. We demonstrate the successful de novo discovery of small-molecule protein ligands from PELs by affinity selection against carbonic anhydrase IX and the oncogenic protein targets BRD4(1) an

SUBMITTER: Rossler SL 

PROVIDER: S-EPMC10064805 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature