Structural insights into G-quadruplexes: towards new anticancer drugs.

Structural insights into G-quadruplexes: towards new anticancer drugs.
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DOI:
10.4155/fmc.09.172
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发表时间:
2010-04
影响因子:
4.2
通讯作者:
Okamoto K
Okamoto K
中科院分区:
医学3区
文献类型:
--
作者:
Yang D;Okamoto K

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DNA G-四链体是在特定的富含G的序列中形成的DNA二级结构。可以形成G-四链体的DNA序列已经在具有生物学意义的区域中被发现,例如人类端粒和癌基因启动子区域。DNA G-四链体是近年来出现的一类新型抗癌药物的分子靶点。将讨论在人类端粒和人类癌基因启动子区形成的生物相关G-四链体结构研究的最新进展,以及G-四链体相互作用药物设计和开发的最新进展。DNA G-四链体可以在生理条件下在溶液中容易地形成,并且是球状折叠的核酸结构。分子内G-四链体的分子结构似乎彼此不同,因此,原则上可以通过不同的蛋白质和药物进行差异调节和靶向。
DNA G-quadruplexes are DNA secondary structures formed in specific G-rich sequences. DNA sequences that can form G-quadruplexes have been found in regions with biological significance, such as human telomeres and oncogene-promoter regions. DNA G-quadruplexes have recently emerged as a new class of novel molecular targets for anticancer drugs. Recent progress on structural studies of the biologically relevant G-quadruplexes formed in human telomeres and in the promoter regions of human oncogenes will be discussed, as well as recent advances in the design and development of G-quadruplex-interactive drugs. DNA G-quadruplexes can readily form in solution under physiological conditions and are globularly folded nucleic acid structures. The molecular structures of intramolecular G-quadruplexes appear to differ from one another and, therefore, in principle may be differentially regulated and targeted by different proteins and drugs.
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