Privileged molecules for protein binding identified from NMR-based screening
Privileged molecules for protein binding identified from NMR-based screening
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DOI：
10.1021/jm000164q
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发表时间：
2000-09-07
影响因子：
7.3
通讯作者：
Fesik, SW
中科院分区：
文献类型：
--
作者：
Hajduk, PJ;Bures, M;Fesik, SW
对11个蛋白质靶标的核磁共振结合数据进行了统计分析，以确定更适合蛋白质结合的分子基序。分析表明，含有联苯亚结构的化合物优先与广泛的蛋白质结合，即使对于这些小分子，也可以实现高水平的特异性(>；250倍)。这些结果表明，富含联苯化合物的高通量筛选文库有望增加产生高亲和力蛋白质配体的机会，它们表明联苯可以作为发现和设计针对广泛蛋白质靶点的高亲和力和特异性的治疗药物的模板。
A statistical analysis of NMR-derived binding data on 11 protein targets was performed to identify molecular motifs that are preferred for protein binding. The analysis indicates that compounds which contain a biphenyl substructure preferentially bind to a wide range of proteins and that high levels of specificity (>250-fold) can be achieved even for these small molecules. These results suggest that high-throughput screening libraries that are enriched with biphenyl-containing compounds can be expected to have increased chances of yielding high-affinity ligands for proteins, and they suggest that the biphenyl can be utilized as a template for the discovery and design of therapeutics with high affinity and specificity for a broad range of protein targets.