Abstract
Higher-ordered structure motifs of nucleic acids, such as the G-quadruplex (G-4), mismatched and bulge structures, are significant research targets because these structures are involved in genetic control and diseases. Selective alkylation of these higher-order structures is challenging due to the chemical instability of the alkylating agent and side-reactions with the single- or double-strand DNA and RNA. We now report the reactive OFF-ON type alkylating agents, vinyl-quinazolinone (VQ) precursors with a sulfoxide, thiophenyl or thiomethyl group for the OFF-ON control of the vinyl reactivity. The stable VQ precursors conjugated with aminoacridine, which bind to the G-4 DNA, selectively reacted with a T base on the G-4 DNA in contrast to the single- and double-strand DNA. Additionally, the VQ precursor reacted with the T or U base in the AP-site, G-4 RNA and T-T mismatch structures. These VQ precursors would be a new candidate for the T or U specific alkylation in the higher-ordered structures of nucleic acids.
Highlights
To a solution of compound 6 (41 mg, 0.13 mmol) in DCM (0.2 mL), were added triisopropyl silane (40 μL, 0.19 mmol) and TFA (0.82 mL), the reaction mixture was stirred at room temperature
To a solution of compound 10 (14 mg, 0.03 mmol) in DCM (0.2 mL) was added TFA (0.95 mL) the reaction mixture was stirred at room temperature for 2h
To the reaction mixture were added HBTU (15 mg, 0.04 mmol), HOBt (5.3 mg, 0.04 mmol), DIPEA (58 μL, 0.33 mmol) and the reaction mixture was stirred at room temperature
Summary
To a solution of compound 10 (14 mg, 0.03 mmol) in DCM (0.2 mL) was added TFA (0.95 mL) the reaction mixture was stirred at room temperature for 2h.
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