A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor

We present herein a novel dissection-then-evolution strategy for ligand optimization. Using the co-crystal structure of the smoothened receptor (SMO) as a guide, we studied the modular contribution of LY2940680 by systematically “silencing” the specific interaction between the individual residue(s)...

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Detalles Bibliográficos
Autores principales: Ye, Lintao, Ding, Kang, Zhao, Fei, Liu, Xiaoyan, Wu, Yiran, Liu, Yang, Xue, Dongxiang, Zhou, Fang, Zhang, Xianjun, Stevens, Raymond C., Xu, Fei, Zhao, Suwen, Tao, Houchao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2017
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072208/
https://www.ncbi.nlm.nih.gov/pubmed/30108845
http://dx.doi.org/10.1039/c7md00104e
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author Ye, Lintao
Ding, Kang
Zhao, Fei
Liu, Xiaoyan
Wu, Yiran
Liu, Yang
Xue, Dongxiang
Zhou, Fang
Zhang, Xianjun
Stevens, Raymond C.
Xu, Fei
Zhao, Suwen
Tao, Houchao
author_facet Ye, Lintao
Ding, Kang
Zhao, Fei
Liu, Xiaoyan
Wu, Yiran
Liu, Yang
Xue, Dongxiang
Zhou, Fang
Zhang, Xianjun
Stevens, Raymond C.
Xu, Fei
Zhao, Suwen
Tao, Houchao
author_sort Ye, Lintao
collection PubMed
description We present herein a novel dissection-then-evolution strategy for ligand optimization. Using the co-crystal structure of the smoothened receptor (SMO) as a guide, we studied the modular contribution of LY2940680 by systematically “silencing” the specific interaction between the individual residue(s) and the fragment in the ligand. Following evolution by focusing on the benzoyl part finally yielded an improved ligand 21.
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spelling pubmed-60722082018-08-14 A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor Ye, Lintao Ding, Kang Zhao, Fei Liu, Xiaoyan Wu, Yiran Liu, Yang Xue, Dongxiang Zhou, Fang Zhang, Xianjun Stevens, Raymond C. Xu, Fei Zhao, Suwen Tao, Houchao Medchemcomm Chemistry We present herein a novel dissection-then-evolution strategy for ligand optimization. Using the co-crystal structure of the smoothened receptor (SMO) as a guide, we studied the modular contribution of LY2940680 by systematically “silencing” the specific interaction between the individual residue(s) and the fragment in the ligand. Following evolution by focusing on the benzoyl part finally yielded an improved ligand 21. Royal Society of Chemistry 2017-04-28 /pmc/articles/PMC6072208/ /pubmed/30108845 http://dx.doi.org/10.1039/c7md00104e Text en This journal is © The Royal Society of Chemistry 2017 http://creativecommons.org/licenses/by-nc/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0)
spellingShingle Chemistry
Ye, Lintao
Ding, Kang
Zhao, Fei
Liu, Xiaoyan
Wu, Yiran
Liu, Yang
Xue, Dongxiang
Zhou, Fang
Zhang, Xianjun
Stevens, Raymond C.
Xu, Fei
Zhao, Suwen
Tao, Houchao
A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor
title A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor
title_full A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor
title_fullStr A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor
title_full_unstemmed A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor
title_short A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor
title_sort structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072208/
https://www.ncbi.nlm.nih.gov/pubmed/30108845
http://dx.doi.org/10.1039/c7md00104e
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