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首页> 外文期刊>Biochemistry >Role of the Heat Capacity Change in Understanding and Modeling Melting Thermodynamics of Complementary Duplexes Containing Standard and Nucleobase-Modified LNA
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Role of the Heat Capacity Change in Understanding and Modeling Melting Thermodynamics of Complementary Duplexes Containing Standard and Nucleobase-Modified LNA

机译：含有标准和核酸酶改性LNA的互补双链体的理解和建模熔化热力学的作用

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摘要

Melting thermodynamic data obtained by differential scanning calorimetry (DSC) are reported for 43 duplexed oligonucleotides containing one or more locked nucleic acid (LNA) substitutions. The measured heat capacity change (Delta C(p)) for the helix-to-coil transition is used to compute the changes in enthalpy and entropy for melting of an LNA-bearing duplex at the T(m) of its corresponding isosequential unmodified DNA duplex to allow rigorous thermodynamic analysis of the stability enhancements provided by LNA substitutions. Contrary to previous studies, our analysis shows that the origin of the improved stability is almost exclusively a net reduction (Delta Delta S degrees < 0) in the entropy gain accompanying the helix-to-coil transition, with the magnitude of the reduction dependent on the type of nucleobase and its base pairing properties. This knowledge and our average measured value for Delta C(p) of 42 +/- 11 cal mol(-1) K(-1) bp(-1) are then used to derive a new model that accurately predicts melting thermodynamics and the increased melting temperature (Delta T(m)) of heteroduplexes formed between an unmodified DNA strand and a complementary strand containing any number and configuration of standard LNA nucleotides A, T, C, and G. This single-base thermodynamic (SBT) model requires only four entropy-related parameters in addition to Delta C(p). Finally, DSC data for 20 duplexes containing the nucleobase-modified LNAs 2-aminoadenine (D) and 2-thiothymine (H) are reported and used to determine SBT model parameters for D and H. The data and model suggest that along with the greater stability enhancement provided by D and H bases relative to their corresponding A and T analogues, the unique pseudocomplementary properties of D-H base pairs may make their use appealing for in vitro and in vivo applications.
机译：据报道，含有差示扫描量热法（DSC）获得的熔化热力学数据，用于含有一种或多种锁定的核酸（LNA）取代的43个双链寡核苷酸。用于螺旋到线圈转变的测量的热容量变化（Delta C（P））用于计算焓和熵的变化，以熔化其相应的异质未改性DNA的T（M）的LNA承载双链体双工以允许LNA取代提供的稳定性增强的严格热力学分析。与先前的研究相反，我们的分析表明，提高稳定性的来源几乎完全是伴随螺旋到线圈过渡的熵增益中的净减少（Delta Delta S度<0），其减少的幅度依赖于此核碱基的类型及其基部配对性能。然后，这种知识和我们的平均测量值为42 +/- 11 cal mol（-1）k（-1）bp（-1）的Δc（p）来得出一种准确预测熔化热力学和熔化热力学和所述的新模型增加熔融温度（ΔT（m）的异渗在未经修饰的DNA链和含有标准LNA核苷酸A，T，C和G的任何数量和构型的互补链中形成的互补链。该单碱基热力学（SBT）模型需要除了Delta C（p）之外，只有四个熵相关参数。最后，报告了含有核碱基改性的LNA 2-氨基核（D）和2-硫甲内氨基（D）和2-硫胺（H）的20个双链体的DSC数据，用于确定D和H的SBT模型参数。数据和模型表明与更大的数据D和H碱相对于它们的相应A和T类似物提供的稳定性增强，DH碱基对的独特假致特性属性可以在体外和体内应用中使用吸引力。

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