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在药物发现中使用小分子结构来补充蛋白质-配体晶体结构。

The use of small-molecule structures to complement protein-ligand crystal structures in drug discovery.

机构信息

Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, England.

出版信息

Acta Crystallogr D Struct Biol. 2017 Mar 1;73(Pt 3):240-245. doi: 10.1107/S2059798317000675. Epub 2017 Feb 22.

DOI:10.1107/S2059798317000675
PMID:28291759
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5349436/
Abstract

Many ligand-discovery stories tell of the use of structures of protein-ligand complexes, but the contribution of structural chemistry is such a core part of finding and improving ligands that it is often overlooked. More than 800 000 crystal structures are available to the community through the Cambridge Structural Database (CSD). Individually, these structures can be of tremendous value and the collection of crystal structures is even more helpful. This article provides examples of how small-molecule crystal structures have been used to complement those of protein-ligand complexes to address challenges ranging from affinity, selectivity and bioavailability though to solubility.

摘要

许多配体发现的故事都讲述了使用蛋白质-配体复合物的结构，但结构化学的贡献是发现和改进配体的核心部分，因此经常被忽视。通过剑桥结构数据库 (CSD)，社区可以获得超过 800000 个晶体结构。这些结构本身就具有巨大的价值，而晶体结构的集合甚至更有帮助。本文提供了一些例子，说明如何使用小分子晶体结构来补充蛋白质-配体复合物的结构，以解决从亲和力、选择性和生物利用度到溶解度等方面的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/7f230bc10e68/d-73-00240-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/ba5d13ba6f94/d-73-00240-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/cc4bc71fde5f/d-73-00240-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/aaafaca0ef49/d-73-00240-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/9f8aea007084/d-73-00240-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/e66b994a2431/d-73-00240-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/0d3c47acbfaa/d-73-00240-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/7f230bc10e68/d-73-00240-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/ba5d13ba6f94/d-73-00240-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/cc4bc71fde5f/d-73-00240-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/aaafaca0ef49/d-73-00240-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/9f8aea007084/d-73-00240-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/e66b994a2431/d-73-00240-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/0d3c47acbfaa/d-73-00240-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b98/5349436/7f230bc10e68/d-73-00240-fig7.jpg

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