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Article: Selection of DNA‐Encoded Dynamic Chemical Libraries for Direct Inhibitor Discovery

TitleSelection of DNA‐Encoded Dynamic Chemical Libraries for Direct Inhibitor Discovery
Authors
KeywordsDNA
DNA-encoded dynamic libraries
drug discovery
dynamic combinatorial libraries
high-throughput screening
Issue Date2020
PublisherWiley - VCH Verlag GmbH & Co. KGaA. The Journal's web site is located at https://onlinelibrary.wiley.com/journal/15213773
Citation
Angewandte Chemie (International Edition), 2020, v. 59 n. 35, p. 14965-14972 How to Cite?
AbstractDynamic combinatorial libraries (DCLs) is a powerful tool for ligand discovery in biomedical research; however, the application of DCLs has been hampered by their low diversity. Recently, the concept of DNA encoding has been employed in DCLs to create DNA‐encoded dynamic libraries (DEDLs); however, all current DEDLs are limited to fragment identification, and a challenging process of fragment linking is required after selection. We report an anchor‐directed DEDL approach that can identify full ligand structures from large‐scale DEDLs. This method is also able to convert unbiased libraries into focused ones targeting specific protein classes. We demonstrated this method by selecting DEDLs against five proteins, and novel inhibitors were identified for all targets. Notably, several selective BD1/BD2 inhibitors were identified from the selections against bromodomain 4 (BRD4), an important anti‐cancer drug target. This work may provide a broadly applicable method for inhibitor discovery.
Persistent Identifierhttp://hdl.handle.net/10722/288040
ISSN
2019 Impact Factor: 12.959
2015 SCImago Journal Rankings: 6.229

 

DC FieldValueLanguage
dc.contributor.authorDeng, Y-
dc.contributor.authorPeng, J-
dc.contributor.authorXiong, F-
dc.contributor.authorSong, Y-
dc.contributor.authorZhou, Y-
dc.contributor.authorZhang, J-
dc.contributor.authorLam, FS-
dc.contributor.authorXie, C-
dc.contributor.authorShen, W-
dc.contributor.authorHuang, Y-
dc.contributor.authorMeng, L-
dc.contributor.authorLi, X-
dc.date.accessioned2020-10-05T12:06:59Z-
dc.date.available2020-10-05T12:06:59Z-
dc.date.issued2020-
dc.identifier.citationAngewandte Chemie (International Edition), 2020, v. 59 n. 35, p. 14965-14972-
dc.identifier.issn1433-7851-
dc.identifier.urihttp://hdl.handle.net/10722/288040-
dc.description.abstractDynamic combinatorial libraries (DCLs) is a powerful tool for ligand discovery in biomedical research; however, the application of DCLs has been hampered by their low diversity. Recently, the concept of DNA encoding has been employed in DCLs to create DNA‐encoded dynamic libraries (DEDLs); however, all current DEDLs are limited to fragment identification, and a challenging process of fragment linking is required after selection. We report an anchor‐directed DEDL approach that can identify full ligand structures from large‐scale DEDLs. This method is also able to convert unbiased libraries into focused ones targeting specific protein classes. We demonstrated this method by selecting DEDLs against five proteins, and novel inhibitors were identified for all targets. Notably, several selective BD1/BD2 inhibitors were identified from the selections against bromodomain 4 (BRD4), an important anti‐cancer drug target. This work may provide a broadly applicable method for inhibitor discovery.-
dc.languageeng-
dc.publisherWiley - VCH Verlag GmbH & Co. KGaA. The Journal's web site is located at https://onlinelibrary.wiley.com/journal/15213773-
dc.relation.ispartofAngewandte Chemie (International Edition)-
dc.rightsThis is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.-
dc.subjectDNA-
dc.subjectDNA-encoded dynamic libraries-
dc.subjectdrug discovery-
dc.subjectdynamic combinatorial libraries-
dc.subjecthigh-throughput screening-
dc.titleSelection of DNA‐Encoded Dynamic Chemical Libraries for Direct Inhibitor Discovery-
dc.typeArticle-
dc.identifier.emailDeng, Y: dengyq@HKUCC-COM.hku.hk-
dc.identifier.emailZhou, Y: yuchow@hku.hk-
dc.identifier.emailZhang, J: chembiol@HKUCC-COM.hku.hk-
dc.identifier.emailHuang, Y: huangyr0@hku.hk-
dc.identifier.emailLi, X: xiaoyuli@hku.hk-
dc.identifier.authorityLi, X=rp02080-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/anie.202005070-
dc.identifier.pmid32436364-
dc.identifier.scopuseid_2-s2.0-85086318865-
dc.identifier.hkuros315338-
dc.identifier.volume59-
dc.identifier.issue35-
dc.identifier.spage14965-
dc.identifier.epage14972-
dc.publisher.placeGermany-

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