Influence of substituent modifications on the binding of 2-amino-1,8-naphthyridines to cytosine opposite an AP site in DNA duplexes: Thermodynamic characterization

Yusuke Sato, Seiichi Nishizawa, Keitaro Yoshimoto, Takehiro Seino, Toshiki Ichihashi, Kotaro Morita, Norio Teramae

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69 Citations (Scopus)

Abstract

Here, we report on a significant effect of substitutions on the binding affinity of a series of 2-amino-1,8-naphthyridines, i.e., 2-amino-1,8-naphthyridine (AND), 2-amino-7-methyl-1,8-naphthyridine (AMND), 2-amino-5,7-dimethyl-1,8-naphthyridine (ADMND) and 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND), all of which can bind to cytosine opposite an AP site in DNA duplexes. Fluorescence titration experiments show that the binding affinity for cytosine is effectively enhanced by the introduction of methyl groups to the naphthyridine ring, and the 1:1 binding constant (106M-1) follows in the order of AND (0.30) > AMND (2.7) > ADMND (6.1) > ATMND (19) in solutions containing 110 mM Na+ < (pH 7.0, at 20°C). The thermodynamic parameters obtained by isothermal titration calorimetry experiments indicate that the introduction of methyl groups effectively reduces the loss of binding entropy, which is indeed responsible for the increase in the binding affinity. The heat capacity change (ΔCp), as determined from temperature dependence of the binding enthalpy, is found to be significantly different between AND (-161 cal/mol K) and ATMND (-217 cal/mol K). The hydrophobic contribution appears to be a key force to explain the observed effect of substitutions on the binding affinity when the observed binding free energy (ΔGobs) is dissected into its component terms.

Original languageEnglish
Pages (from-to)1411-1422
Number of pages12
JournalNucleic acids research
Volume37
Issue number5
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Genetics

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