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

点击翻译按钮获取中文摘要

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