TY - JOUR
T1 - Reactive OFF-ON type alkylating agents for higher-ordered structures of nucleic acids
AU - Onizuka, Kazumitsu
AU - Hazemi, Madoka E.
AU - Sato, Norihiro
AU - Tsuji, Gen Ichiro
AU - Ishikawa, Shunya
AU - Ozawa, Mamiko
AU - Tanno, Kousuke
AU - Yamada, Ken
AU - Nagatsugi, Fumi
N1 - Funding Information:
The author (M.E.H.) gratefully acknowledges scholarship support throughout master’s degree from Sato Yo International Scholarship Foundation (SISF). The authors are grateful to Dr Y. Yamaoki and Prof. M. Katahira at Kyoto University and D. Unabara at Tohoku University for supporting 2D NMR measurements.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2019/7/26
Y1 - 2019/7/26
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/gkz512
DO - 10.1093/nar/gkz512
M3 - Article
C2 - 31188442
AN - SCOPUS:85070183193
VL - 47
SP - 6578
EP - 6589
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 13
ER -