Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library

A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating...

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Autores principales: Litovchick, Alexander, Dumelin, Christoph E., Habeshian, Sevan, Gikunju, Diana, Guié, Marie-Aude, Centrella, Paolo, Zhang, Ying, Sigel, Eric A., Cuozzo, John W., Keefe, Anthony D., Clark, Matthew A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603778/
https://www.ncbi.nlm.nih.gov/pubmed/26061191
http://dx.doi.org/10.1038/srep10916
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author Litovchick, Alexander
Dumelin, Christoph E.
Habeshian, Sevan
Gikunju, Diana
Guié, Marie-Aude
Centrella, Paolo
Zhang, Ying
Sigel, Eric A.
Cuozzo, John W.
Keefe, Anthony D.
Clark, Matthew A.
author_facet Litovchick, Alexander
Dumelin, Christoph E.
Habeshian, Sevan
Gikunju, Diana
Guié, Marie-Aude
Centrella, Paolo
Zhang, Ying
Sigel, Eric A.
Cuozzo, John W.
Keefe, Anthony D.
Clark, Matthew A.
author_sort Litovchick, Alexander
collection PubMed
description A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library, and successfully identified inhibitors of the enzyme soluble epoxide hydrolase.
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spelling pubmed-46037782015-10-23 Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library Litovchick, Alexander Dumelin, Christoph E. Habeshian, Sevan Gikunju, Diana Guié, Marie-Aude Centrella, Paolo Zhang, Ying Sigel, Eric A. Cuozzo, John W. Keefe, Anthony D. Clark, Matthew A. Sci Rep Article A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library, and successfully identified inhibitors of the enzyme soluble epoxide hydrolase. Nature Publishing Group 2015-06-10 /pmc/articles/PMC4603778/ /pubmed/26061191 http://dx.doi.org/10.1038/srep10916 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Litovchick, Alexander
Dumelin, Christoph E.
Habeshian, Sevan
Gikunju, Diana
Guié, Marie-Aude
Centrella, Paolo
Zhang, Ying
Sigel, Eric A.
Cuozzo, John W.
Keefe, Anthony D.
Clark, Matthew A.
Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library
title Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library
title_full Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library
title_fullStr Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library
title_full_unstemmed Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library
title_short Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library
title_sort encoded library synthesis using chemical ligation and the discovery of seh inhibitors from a 334-million member library
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603778/
https://www.ncbi.nlm.nih.gov/pubmed/26061191
http://dx.doi.org/10.1038/srep10916
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