title: Existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy.
abstract: Existence of G-quadruplex DNA in vivo always attract widespread interest in the field of biology and biological chemistry. We reported our findings for the existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy. Probes for selective G-quadruplex cross-linking was designed and synthesized that show high selectivity for G-quadruplex cross-linking. Further biological studies demonstrated its good inhibition activity against murine melanoma cells. To further investigate if G-quadruplex DNA was formed in vivo and as the target, a derivative was synthesized and pull-down process toward chromosome DNAs combined with circular dichroism and high throughput deep sequencing were performed. Several simulated intracellular conditions, including X. laevis oocytes, Ficoll 70 and PEG, was used to investigate the compound's pure cross-linking ability upon preformed G-quadruplex. Thus, as a potent G-quadruplex cross-linking agent, our strategy provided both valuable evidence of G-quadruplex structures in vivo and intense potential in anti-cancer therapy.
authors: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei, 430072, P R China.
authors: Libo
authors: L
authors: Yuan
authors: Tian
authors: T
authors: Tian
authors: Yuqi
authors: Y
authors: Chen
authors: Shengyong
authors: S
authors: Yan
authors: Xiwen
authors: X
authors: Xing
authors: Zhengan
authors: Z
authors: Zhang
authors: Qianqian
authors: Q
authors: Zhai
authors: Liang
authors: L
authors: Xu
authors: Shaoru
authors: S
authors: Wang
authors: Xiaocheng
authors: X
authors: Weng
authors: Bifeng
authors: B
authors: Yuan
authors: Yuqi
authors: Y
authors: Feng
authors: Xiang
authors: X
authors: Zhou
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002942:Circular Dichroism; D020552:Comet Assay; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D005362:Ficoll / Q000378:metabolism; D054856:G-Quadruplexes; D006367:HeLa Cells; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009857:Oncogenes / Q000235:genetics*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010655:Phenylenediamines / Q000138:chemical synthesis / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D012545:Schiff Bases / Q000138:chemical synthesis / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
chemical_list: D003432:Cross-Linking Reagents; D010655:Phenylenediamines; D012545:Schiff Bases; D005362:Ficoll; D011092:Polyethylene Glycols; D004247:DNA
references: J Am Chem Soc. 2010 Nov 3;132(43):15321-7
references: 20939569
references: Angew Chem Int Ed Engl. 2009;48(12):2188-91
references: 19199323
references: J Am Chem Soc. 2011 Nov 30;133(47):19153-9
references: 22007660
references: Nat Rev Drug Discov. 2011 Apr;10(4):261-75
references: 21455236
references: Science. 1984 Apr 20;224(4646):256-62
references: 6538699
references: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11593-8
references: 12195017
references: Angew Chem Int Ed Engl. 2010 Jul 19;49(31):5305-9
references: 20572238
references: Angew Chem Int Ed Engl. 2008;47(14):2677-80
references: 18300215
references: Nucleic Acids Res. 2005 May 24;33(9):2908-16
references: 15914667
references: J Am Chem Soc. 2004 Jul 21;126(28):8710-6
references: 15250723
references: Chem Biol Interact. 2010 Oct 6;188(1):1-14
references: 20685355
references: Org Biomol Chem. 2012 Apr 14;10(14):2798-806
references: 22367401
references: Biochimie. 2011 Aug;93(8):1328-40
references: 21699955
references: ChemMedChem. 2008 May;3(5):690-713
references: 18236491
references: Bioorg Med Chem. 2010 Jun 1;18(11):4042-8
references: 20452224
references: J Ethnopharmacol. 2010 Jun 16;129(3):387-90
references: 20430091
references: Science. 1988 Jul 22;241(4864):456-9
references: 3293213
references: J Am Chem Soc. 2005 Mar 9;127(9):2944-59
references: 15740131
references: J Med Chem. 2011 Aug 25;54(16):5671-9
references: 21774525
references: Cancer Res. 2009 Oct 1;69(19):7653-61
references: 19738048
references: Dalton Trans. 2010 Aug 21;39(31):7330-7
references: 20601980
references: Proc Natl Acad Sci U S A. 1989 Dec;86(24):9682-6
references: 2690070
references: J Am Chem Soc. 2009 Sep 16;131(36):13132-41
references: 19694465
references: Cancer Res. 2003 Sep 15;63(18):6016-25
references: 14522930
references: Nature. 1991 Apr 25;350(6320):718-20
references: 2023635
references: Nat Chem. 2013 Mar;5(3):182-6
references: 23422559
references: J Am Chem Soc. 2003 Feb 5;125(5):1116-7
references: 12553783
references: Angew Chem Int Ed Engl. 2009;48(18):3281-4
references: 19334028
references: Nucleic Acids Res. 2011 Jul;39(13):5768-75
references: 21450807
references: Nat Biotechnol. 2011 Jan;29(1):68-72
references: 21151123
references: Nat Chem Biol. 2010 Aug;6(8):621-9
references: 20581822
references: Nat Chem Biol. 2012 Feb 05;8(3):301-10
references: 22306580
references: Nucleic Acids Res. 1981 Jul 10;9(13):3015-27
references: 6269069
references: Nat Chem. 2010 Dec;2(12):1095-8
references: 21107376
references: Mol Cancer Ther. 2002 Jun;1(8):565-73
references: 12479216
references: Mutagenesis. 2010 Mar;25(2):133-8
references: 19892777
references: Angew Chem Int Ed Engl. 2007;46(42):8020-3
references: 17853519
references: Nucleic Acids Res. 2010 Jan;38(1):327-38
references: 19858105
references: Angew Chem Int Ed Engl. 2011 Nov 4;50(45):10645-8
references: 21928459
references: Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8572-7
references: 11438689
references: Angew Chem Int Ed Engl. 2007;46(28):5405-7
references: 17562537
references: Cell. 1984 Jun;37(2):381-91
references: 6327064