Nucleic Acids Research Advance Access originally published online on January 9, 2009
Nucleic Acids Research 2009 37(5):1411-1422; doi:10.1093/nar/gkn1079
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Nucleic Acids Research, 2009, Vol. 37, No. 5 1411-1422
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Chemistry and Synthetic Biology |
Influence of substituent modifications on the binding of 2-amino-1,8-naphthyridines to cytosine opposite an AP site in DNA duplexes: thermodynamic characterization
1Department of Chemistry, Graduate School of Science, Tohoku University, and CREST, Japan Science and Technology Agency (JST), Aoba-ku, Sendai 980-8578 and 2Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1-Ten-noudai, Tsukuba, Ibaraki 305-8573, Japan
*To whom correspondence should be addressed. Tel: +81 22 795 6549; Fax: +81 22 795 6552; Email: teramae{at}mail.tains.tohoku.ac.jp
Received September 1, 2008. Revised December 22, 2008. Accepted December 23, 2008.
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 (106 M–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 (
Cp), 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 (Gobs) is dissected into its component terms.
Present address: Kotaro Morita, Department of Chemistry, Faculty of Science, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan