Abiotic peptides as carriers of information for the encoding of small-molecule library synthesis.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
03 03 2023
03 03 2023
Historique:
entrez:
2
3
2023
pubmed:
3
3
2023
medline:
7
3
2023
Statut:
ppublish
Résumé
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) and MDM2. Collectively, this work establishes abiotic peptides as carriers of information for the encoding of small-molecule synthesis, leveraged herein for the discovery of protein ligands.
Identifiants
pubmed: 36862767
doi: 10.1126/science.adf1354
pmc: PMC10064805
mid: NIHMS1881119
doi:
Substances chimiques
Ligands
0
Nuclear Proteins
0
Peptide Library
0
Peptides
0
Transcription Factors
0
Small Molecule Libraries
0
BRD4 protein, human
0
Carbonic Anhydrase IX
EC 4.2.1.1
MDM2 protein, human
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
939-945Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM122483
Pays : United States
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