锌指结构域作为金属基化合物的治疗靶标–更新,Metallomics

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锌指结构域作为金属基化合物的治疗靶标–更新
Metallomics ( IF 2.9 ) Pub Date : 2018-09-25 00:00:00 , DOI: 10.1039/c8mt00262b
C. Abbehausen _{1,

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Affiliation

锌指蛋白是最丰富的蛋白家族之一，具有广泛的结构和功能。结构性锌离子提供正确的构象以特异性识别DNA，RNA和蛋白质序列。锌指在转录，蛋白质降解，DNA修复，细胞迁移等方面具有基本功能。最近，已经发表了有关锌指广泛参与疾病的报道。另一方面，随着许多基因组和蛋白质组的报道，仍有许多信息尚待阐明。已经发现了各种锌指。但是，它们的功能仍在调查中。由于锌指已在多种疾病中确定功能，因此它们被越来越多地视为药物靶标。Zn（II）的替代）被锌指中的另一种金属离子抑制是最突出的方法之一。从一方面来看，锌指在Ni（II），Hg（II），Cd（II）等的毒性机制中起作用。另一方面，金，铂，钴和硒络合物是被开发为治疗用锌指抑制剂的化合物。设计治疗性锌指抑制剂的主要挑战是实现选择性。近来，新型化合物的设计和锌取代机理的阐明更新了金属络合物选择性抑制锌指的可能性。这篇综述旨在更新通过金属络合物选择性靶向锌指结构域的新策略的现状。

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Zinc finger domains as therapeutic targets for metal-based compounds – an update

Zinc finger proteins are one of the most abundant families of proteins and present a wide range of structures and functions. The structural zinc ion provides the correct conformation to specifically recognize DNA, RNA and protein sequences. Zinc fingers have essential functions in transcription, protein degradation, DNA repair, cell migration, and others. Recently, reports on the extensive participation of zinc fingers in disease have been published. On the other hand, much information remains to be unravelled as many genomes and proteomes are being reported. A variety of zinc fingers have been identified; however, their functions are still under investigation. Because zinc fingers have identified functions in several diseases, they are being increasingly recognized as drug targets. The replacement of Zn(II) by another metal ion in zinc fingers is one of the most prominent methods of inhibition. From one side, zinc fingers play roles in the toxicity mechanisms of Ni(II), Hg(II), Cd(II) and others. From the other side, gold, platinum, cobalt, and selenium complexes are amongst the compounds being developed as zinc finger inhibitors for therapy. The main challenge in the design of therapeutic zinc finger inhibitors is to achieve selectivity. Recently, the design of novel compounds and elucidation of the mechanisms of zinc substitution have renewed the possibilities of selective zinc finger inhibition by metal complexes. This review aims to update the status of novel strategies to selectively target zinc finger domains by metal complexes.

更新日期：2018-09-25

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