A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor.
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ABSTRACT:
SUBMITTER: Ye L
PROVIDER: S-EPMC6072208 | biostudies-other | 2017 Jun
REPOSITORIES: biostudies-other
Publications
A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor.
Ye Lintao L Ding Kang K Zhao Fei F Liu Xiaoyan X Wu Yiran Y Liu Yang Y Xue Dongxiang D Zhou Fang F Zhang Xianjun X Stevens Raymond C RC Xu Fei F Zhao Suwen S Tao Houchao H
MedChemComm 20170428 6
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 <b>21</b>. ...[more]
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