Structure elucidation of human telomeric DNA and RNA in cells by chemical approach and its application

研究重点是：(1)利用化学方法了解人类端粒DNA和RNA的结构和功能；(2)开发针对人类端粒和端粒酶的各种化学方法来治疗癌症。核磁共振显示，人类端粒RNA形成一个平行的G -四重结构(J. Am.；化学。Soc. 132,7231, 2010.)。利用光开关探针，我们发现人类端粒RNA在活细胞中形成平行的G -四重体结构，为G -四重体在人类中存在提供了体内证据。学会科学。美国。[107] .北京：北京交通大学，2010。此外，我们证明了小RNA稳定的mRNA结构抑制了人类细胞中的翻译。我们还成功地利用端粒G-四重结构的DNA Nanomechan检测了生物分子（Nature communications 2011:449doi:10.1038/ncomms 1452）。我们开发了一种检测个体端粒长度（DITL）的方法，该方法使用基于化学的方法…More h可以准确地测量个体染色体的端粒长度。化学。Soc. 135,14,2013 .)。我们使用了一个模型系统来提供关于G -四重体结构形成的证据，这些结构涉及端粒DNA和RNA序列，它们有可能为端粒末端提供保护性的盖层结构（J. Biol.）。化学学报，2011,31(1),2012。．我们用光交联试剂开发了一个小的6聚寡核苷酸，在光照射下与人端粒dna发生有效的光交联。化学。Soc. 132, 631, 2010。)． 我们报道了手性环状螺旋烯对四重DNA的对映选择性识别的第一个例子。化学。Soc. 132, 3778, 2010。)． 此外，我们证明了单肽核酸（PNA）通过形成PNA/DNA杂交G-四重体（Angew.）有效地靶向双链DNA中富含G的区域。化学。Int。编辑51,7198,2012)。我们还发表了三篇关于本研究的综述论文(化学。Soc。Rev. 2011, 40,2719; Methods . 57,100,2012；制药。Des。18、2096、2012)。． 少

The researches focus on (1) Understanding the structures and functions of human telomere DNA and RNA by chemical approaches, (2) Developing various chemical methods to targeting human telomeres and telomerase for t he treatment of cancer.The NMR showed that human telomere RNA forms a parallel G - quadruplex structure (J. Am. Chem. Soc. 132,7231, 2010.). Using a light - switching probe, we found that human telomere RNA forms a parallel G - quadruplex structure in living ce lls, providing the in vivo evidence for the presence of the G - quadruplex in human (Proc. Natl. Acad. Sci. USA. 107, 14579, 2010.). Furthermore, we demonstrated that small RNA - stabilized mRNA structures inhibit the translation in human cells. We also succes sfully detected the biomolecules by using DNA Nanomechan of telomere G- quadruplex structure (Nature Communcations 2011 2:449doi:10.1038/ncomms 1452 .).We developed a method for detection of individual telomere lengths (DITL) that uses a chemistry- based approac … More h that accurately measures the telomere lengths from individual chromosomes (J. Am. Chem. Soc. 135, 14, 2013.). We have used a model system to provide evidence about the formation of G - quadruplex structures involving telomeric DNA and RNA sequences t hat have the potential to provide a protective capping structure for telomere ends (J. Biol. Chem. 287, 41787, 2012.) .We developed a small 6- mer oligonucleotide with a photo - cross - linking reagent to cause efficient photo - cross - linking to human telomere D NA upon light irradiation（ J. Am. Chem. Soc. 132, 631, 2010. ）. We reported the first example of enantioselective recognition of quadruplex DNA by a chiral cyclic helicene （ J. Am. Chem. Soc. 132, 3778, 2010. ） . Furthermore, we demonstrated that a single peptide nucleic acid (PNA) effe ctively targets the G- rich region in double - stranded DNA through formation of a PNA/DNA hybrid G- quadruplex (Angew. Chem. Int. Ed. 51, 7198, 2012) .We also published three review papers about the researches （Chem. Soc. Rev. 2011, 40, 2719； Methods 57, 100, 2012；Curr. Pharm. Des. 18,2096,2012.) . Less