G-Quadruplex-Specific Cell-Permeable Guanosine–Anthracene Conjugate Inhibits Telomere Elongation and Induces Apoptosis by Repressing the c-MYC Gene
BIOCONJUGATE CHEMISTRY(2019)
摘要
We herein report a cell-membrane-permeable molecular probe ADG, prepared by conjugating guanosine with anthracene, selectively interacts with c-MYC G-quadruplex over other promoter and telomeric quadruplexes as well as duplex DNA. NMR spectroscopy suggests that ADG interacts with terminal G-quartets as well as with the nearby G-rich tract (G13-G14-G15 and G8-G9-G10) of c-MYC quadruplex. In vitro cellular studies indicate that ADG represses c-MYC expression by stabilizing its promoter G-quadruplex and alters c-MYC-related cellular events. ADG suppresses hTERT and BCL2 gene expressions in a promoter-independent manner, inhibits elongation of telomere length, and activates apoptotic cascades in cancer cells.
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关键词
induces apoptosis,g-quadruplex-specific,cell-permeable,c-myc
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