Drugs for 'protein clouds': targeting intrinsically disordered transcription factors
Drugs for 'protein clouds': targeting intrinsically disordered transcription factors
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DOI：
10.1016/j.coph.2010.09.005
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发表时间：
2010-12-01
影响因子：
4
通讯作者：
Uversky, Vladimir N.
中科院分区：
文献类型：
--
作者：
Dunker, A. Keith;Uversky, Vladimir N.
转录因子（Transcription factors, TFs）是一个很有吸引力但又很困难的药物靶点，其困难来自几个方面，包括TFs的结合杂乱性和其结合位点的内在无序性。长期以来，没有明确结构的蛋白质的靶向被认为是不可实现的，现在出现的数据表明，选择性阻断内在无序tf与其蛋白质结合伙伴的特定相互作用是可能的，初始命中已被优化以增加其特异性和亲和力。为了阐明基于内在无序蛋白质的阻断机制，已经阐述了几种策略然而，针对“蛋白质云”的药物开发领域仍然存在挑战，这种开发仍处于早期阶段
Transcription factors (TFs) are very attractive but difficult drug targets The difficulties come from several directions including the binding promiscuity of TFs and the intrinsically disordered nature of their binding sites, which often resemble 'protein clouds For a long time the targeting of proteins without defined structures was considered infeasible Data have now emerged showing that selective blocking of specific interactions of intrinsically disordered TFs with their protein binding partners is possible Initial hits have been optimized to increase their specificity and affinity Several strategies have been elaborated for elucidating the mechanisms of blocking of intrinsic disorder-based protein protein interactions However, challenges remain in the field of drug development for 'protein clouds', such development is still in its earliest stage