Influence of substituent modifications on the binding of 2-amino-1,8-naphthyridines to cytosine opposite an AP site in DNA duplexes: thermodynamic characterization.
Influence of substituent modifications on the binding of 2-amino-1,8-naphthyridines to cytosine opposite an AP site in DNA duplexes: thermodynamic characterization.
复制标题
DOI：
10.1093/nar/gkn1079
复制
发表时间：
2009-04
影响因子：
14.9
通讯作者：
Teramae N
中科院分区：
文献类型：
--
作者：
Sato Y;Nishizawa S;Yoshimoto K;Seino T;Ichihashi T;Morita K;Teramae N
在这里，我们报道了取代对一系列2-氨基-1,8-萘啶的结合亲和力的显著影响，即2-氨基-1,8-萘啶（AND）， 2-氨基-7-甲基-1,8-萘啶（AMND）， 2-氨基-5,7-二甲基-1,8-萘啶（adnd）和2-氨基-5,6,7-三甲基-1,8-萘啶（atnd），它们都可以与DNA双链中AP位点相反的胞嘧啶结合。荧光滴定实验表明，在含110 mM Na+ （pH 7.0, 20°C）的溶液中，甲基的引入有效地增强了胞嘧啶的结合亲和力，并且1:1的结合常数（106 M−1）为and (0.30) < AMND (2.7) < ADMND (6.1) < ATMND（19）。等温滴定量热实验得到的热力学参数表明，甲基的引入有效地减少了结合熵的损失，这确实是结合亲和力增加的原因。根据结合焓的温度依赖性测定的热容变化（ΔCp）在AND （- 161 cal/mol K）和ATMND （- 217 cal/mol K）之间存在显著差异。当观察到的结合自由能（ΔGobs）被分解成其组成项时，疏水贡献似乎是解释所观察到的取代对结合亲和力的影响的关键力量。
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 (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.
登录
查看更多内容
DOI：
10.1073/pnas.85.24.9436
发表时间：
1988-12-01
影响因子：
11.1
作者：
INNIS, MA;MYAMBO, KB;BROW, MAD
通讯作者：
BROW, MAD
影响因子：
14.9
作者：
Barceló, F;Capó, D;Portugal, J
通讯作者：
Portugal, J
DOI：
10.1080/07391102.1983.10507457
发表时间：
1983-01-01
影响因子：
4.4
作者：
MARKY, LA;SNYDER, JG;BRESLAUER, KJ
通讯作者：
BRESLAUER, KJ
影响因子：
3.2
作者：
Morita, Kotaro;Sato, Yusuke;Teramae, Norio
通讯作者：
Teramae, Norio
影响因子：
46.9
作者：
Nakatani, K;Sando, S;Saito, I
通讯作者：
Saito, I