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新型功能复杂性片段文库对结核分枝杆菌 InhA 的筛选。

Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA.

机构信息

Drug Discovery Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.

DPU TB Diseases of the Developing World, Tres Cantos Medicines Development Campus, GlaxoSmithKline Severo Ochoa 2, Tres Cantos, 28760, Madrid, Spain.

出版信息

ChemMedChem. 2018 Apr 6;13(7):672-677. doi: 10.1002/cmdc.201700774. Epub 2018 Feb 19.

DOI:10.1002/cmdc.201700774
PMID:29399991
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5915743/
Abstract

Our findings reported herein provide support for the benefits of including functional group complexity (FGC) within fragments when screening against protein targets such as Mycobacterium tuberculosis InhA. We show that InhA fragment actives with FGC maintained their binding pose during elaboration. Furthermore, weak fragment hits with functional group handles also allowed for facile fragment elaboration to afford novel and potent InhA inhibitors with good ligand efficiency metrics for optimization.

摘要

我们在此报告的研究结果为在针对结核分枝杆菌 InhA 等蛋白质靶标进行筛选时在片段中包含功能基复杂度（FGC）的益处提供了支持。我们表明，具有 FGC 的 InhA 片段活性在进行精细化时保持其结合构象。此外，具有功能基接头的弱片段命中也允许进行易于进行的片段精细化，从而获得具有良好配体效率指标的新型和有效的 InhA 抑制剂，以进行优化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/0fe8b9b1728b/CMDC-13-672-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/3e72cb945764/CMDC-13-672-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/03972d29564f/CMDC-13-672-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/3de4dfc23388/CMDC-13-672-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/496d3c07f16e/CMDC-13-672-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/80c6cee91bc3/CMDC-13-672-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/03090a7a9945/CMDC-13-672-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/0fe8b9b1728b/CMDC-13-672-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/3e72cb945764/CMDC-13-672-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/03972d29564f/CMDC-13-672-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/3de4dfc23388/CMDC-13-672-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/496d3c07f16e/CMDC-13-672-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/80c6cee91bc3/CMDC-13-672-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/03090a7a9945/CMDC-13-672-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb00/5915743/0fe8b9b1728b/CMDC-13-672-g007.jpg

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