Universal encoding of next generation DNA-encoded chemical libraries.
Journal
Chemical science
ISSN: 2041-6520
Titre abrégé: Chem Sci
Pays: England
ID NLM: 101545951
Informations de publication
Date de publication:
26 Jan 2022
26 Jan 2022
Historique:
received:
18
10
2021
accepted:
14
12
2021
entrez:
25
2
2022
pubmed:
26
2
2022
medline:
26
2
2022
Statut:
epublish
Résumé
DNA-encoded chemical libraries (DELs) are useful tools for the discovery of small molecule ligands to protein targets of pharmaceutical interest. Compared with single-pharmacophore DELs, dual-pharmacophore DELs simultaneously display two chemical moieties on both DNA strands, and allow for the construction of highly diverse and pure libraries, with a potential for targeting larger protein surfaces. Although methods for the encoding of simple, fragment-like dual-display libraries have been established, more complex libraries require a different encoding strategy. Here, we present a robust and convenient "large encoding design" (LED), which facilitates the PCR-amplification of multiple codes distributed among two partially complementary DNA strands. We experimentally implemented multiple coding regions and we compared the new DNA encoding scheme with previously reported dual-display DEL modalities in terms of amplifiability and performance in test selections against two target proteins. With the LED methodology in place, we foresee the construction and screening of DELs of unprecedented sizes and designs.
Identifiants
pubmed: 35211261
doi: 10.1039/d1sc05721a
pii: d1sc05721a
pmc: PMC8790773
doi:
Types de publication
Journal Article
Langues
eng
Pagination
967-974Informations de copyright
This journal is © The Royal Society of Chemistry.
Déclaration de conflit d'intérêts
Dario Neri is a co-founder and shareholder of Philochem AG (Otelfingen, Switzerland).
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