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- Publisher Website: 10.1038/s41557-020-00605-x
- Scopus: eid_2-s2.0-85097911824
- PMID: 33349694
- WOS: WOS:000600819300001
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Article: Selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells
Title | Selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells |
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Authors | |
Issue Date | 2021 |
Publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/nchem/index.html |
Citation | Nature Chemistry, 2021, v. 13, p. 77-88 How to Cite? |
Abstract | Membrane proteins on the cell surface perform a myriad of biological functions; however, ligand discovery for membrane proteins is highly challenging, because a natural cellular environment is often necessary to maintain protein structure and function. DNA-encoded chemical libraries (DELs) have emerged as a powerful technology for ligand discovery, but they are mainly limited to purified proteins. Here we report a method that can specifically label membrane proteins with a DNA tag, and thereby enable target-specific DEL selections against endogenous membrane proteins on live cells without overexpression or any other genetic manipulation. We demonstrate the generality and performance of this method by screening a 30.42-million-compound DEL against the folate receptor, carbonic anhydrase 12 and the epidermal growth factor receptor on live cells, and identify and validate a series of novel ligands for these targets. Given the high therapeutic significance of membrane proteins and their intractability to traditional high-throughput screening approaches, this method has the potential to facilitate membrane-protein-based drug discovery by harnessing the power of DEL.
A method to label membrane proteins with a DNA tag has been developed that enables the selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells. As a demonstration, a 30-million-compound DNA-encoded chemical library is screened against folate receptor, carbonic anhydrase 12 and epidermal growth factor receptor on live cells. |
Persistent Identifier | http://hdl.handle.net/10722/297677 |
ISSN | 2023 Impact Factor: 19.2 2023 SCImago Journal Rankings: 6.940 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Huang, YME | - |
dc.contributor.author | MENG, L | - |
dc.contributor.author | NIE, Q | - |
dc.contributor.author | Zhou, Y | - |
dc.contributor.author | CHEN, L | - |
dc.contributor.author | YANG, S | - |
dc.contributor.author | Fung, EYM | - |
dc.contributor.author | Li, X | - |
dc.contributor.author | HUANG, C | - |
dc.contributor.author | CAO, Y | - |
dc.contributor.author | LI, Y | - |
dc.contributor.author | Li, X | - |
dc.date.accessioned | 2021-03-23T04:20:11Z | - |
dc.date.available | 2021-03-23T04:20:11Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Nature Chemistry, 2021, v. 13, p. 77-88 | - |
dc.identifier.issn | 1755-4330 | - |
dc.identifier.uri | http://hdl.handle.net/10722/297677 | - |
dc.description.abstract | Membrane proteins on the cell surface perform a myriad of biological functions; however, ligand discovery for membrane proteins is highly challenging, because a natural cellular environment is often necessary to maintain protein structure and function. DNA-encoded chemical libraries (DELs) have emerged as a powerful technology for ligand discovery, but they are mainly limited to purified proteins. Here we report a method that can specifically label membrane proteins with a DNA tag, and thereby enable target-specific DEL selections against endogenous membrane proteins on live cells without overexpression or any other genetic manipulation. We demonstrate the generality and performance of this method by screening a 30.42-million-compound DEL against the folate receptor, carbonic anhydrase 12 and the epidermal growth factor receptor on live cells, and identify and validate a series of novel ligands for these targets. Given the high therapeutic significance of membrane proteins and their intractability to traditional high-throughput screening approaches, this method has the potential to facilitate membrane-protein-based drug discovery by harnessing the power of DEL. A method to label membrane proteins with a DNA tag has been developed that enables the selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells. As a demonstration, a 30-million-compound DNA-encoded chemical library is screened against folate receptor, carbonic anhydrase 12 and epidermal growth factor receptor on live cells. | - |
dc.language | eng | - |
dc.publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/nchem/index.html | - |
dc.relation.ispartof | Nature Chemistry | - |
dc.title | Selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells | - |
dc.type | Article | - |
dc.identifier.email | Huang, YME: huangyr0@hku.hk | - |
dc.identifier.email | Zhou, Y: yuchow@hku.hk | - |
dc.identifier.email | Fung, EYM: eva.fungym@hku.hk | - |
dc.identifier.email | Li, X: lixm@hku.hk | - |
dc.identifier.email | Li, X: xiaoyuli@hku.hk | - |
dc.identifier.authority | Fung, EYM=rp01986 | - |
dc.identifier.authority | Li, X=rp02080 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1038/s41557-020-00605-x | - |
dc.identifier.pmid | 33349694 | - |
dc.identifier.scopus | eid_2-s2.0-85097911824 | - |
dc.identifier.hkuros | 321750 | - |
dc.identifier.volume | 13 | - |
dc.identifier.spage | 77 | - |
dc.identifier.epage | 88 | - |
dc.identifier.isi | WOS:000600819300001 | - |
dc.publisher.place | United Kingdom | - |