Ma Dik-Lung, Wang Modi, Lin Sheng, Han Quan-Bin, Leung Chung-Hang
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
Curr Top Med Chem. 2015;15(19):1957-63. doi: 10.2174/1568026615666150515150106.
The G-quadruplex structure is a non-canonical secondary DNA motif that is built from planar tetrads of guanine residues stabilized by Hoogsteen-type hydrogen bonding. Bioinformatics studies indicate that sequences rich in guanine that are able to form G-quadruplexes are widely distributed throughout the human genome, particularly in telomere and promoter regions of genes. G-quadruplex sequences found in the promoters of human oncogenes, such as k-ras, c-myc and bcl-2 have attracted particular attention as molecular targets for therapeutic intervention due to their potential capability to regulate gene expression at the transcriptional level. Moreover, the G-quadruplex structure has been associated with a number of human diseases arising from defective telomeric maintenance. Despite intensive research in this area, however, the actual function of G-quadruplexes in vivo has not yet been fully understood. Therefore, significant efforts have been devoted to the discovery of specific probes for visualizing and distinguishing G-quadruplex structures from other nucleic acid molecules likely to be found in biological environments. This review summarizes recent studies in the development of G-quadruplex probes over the past three years, with a particular emphasize on the detection and imaging of G-quadruplex structures within living cells. Furthermore, the detection and biological relevance of RNA G-quadruplexes is discussed.
G-四链体结构是一种非经典的二级DNA基序,由鸟嘌呤残基的平面四联体通过Hoogsteen型氢键稳定而成。生物信息学研究表明,富含鸟嘌呤且能够形成G-四链体的序列广泛分布于整个人类基因组中,尤其是在基因的端粒和启动子区域。在人类癌基因(如k-ras、c-myc和bcl-2)启动子中发现的G-四链体序列,因其在转录水平调控基因表达的潜在能力,作为治疗干预的分子靶点而备受关注。此外,G-四链体结构与许多因端粒维持缺陷引起的人类疾病有关。然而,尽管在该领域进行了深入研究,G-四链体在体内的实际功能尚未完全了解。因此,人们致力于发现特异性探针,以在生物环境中可视化并区分G-四链体结构与其他可能存在的核酸分子。本综述总结了过去三年中G-四链体探针开发的最新研究,特别强调了活细胞内G-四链体结构的检测和成像。此外,还讨论了RNA G-四链体的检测及其生物学相关性。