2-Amino-1,8-naphthyridine Dimer (ANP77), a High-Affinity Binder to the Internal Loops of C/CC and T/CC Sites in Double-Stranded DNA

Bimolendu Das, Konami Nagano, Gota Kawai, Asako Murata, Kazuhiko Nakatani

研究成果: ジャーナルへの寄稿学術誌査読

1 被引用数 (Scopus)

抄録

Small molecules targeting DNA regions with structural fluctuation are an important class of molecule as chemical probes for studying the role of these structures in biological systems and the development of neurological disorders. The molecule ANP77 we described here, where a three-atom linker connects two 2-amino-1,8-naphthyridines at the C7 position, was found to form stacked structure with protonation of naphthyridine at low pH, and bound to the internal loop consisting of C/CC and T/CC in double-stranded DNA with affinities of 4.8 and 34.4 nM, respectively. Mass spectrometry and isothermal titration calorimetry analyses determined the stoichiometry for the binding as 1:1, and chemical footprinting with permanganate and NMR structural analysis revealed that the T in the T/CC was forced to flip out toward an extrahelical position upon ANP77 binding. Protonated stacked ANP77 interacted with two adjacent cytosines through hydrogen bonding and occupied the position in the duplex by flipping out the C or T opposite CC. Finally, this study demonstrated the potential of ANP77 for binding to the sequences of biological significance with the TG(T/C)CC repeat of the PIG3 promoter and the telomere repeat CCCTAA.

本文言語英語
ページ(範囲)340-350
ページ数11
ジャーナルJournal of Organic Chemistry
87
1
DOI
出版ステータス出版済み - 1月 7 2022
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 有機化学

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