Effects of Phosphoryl Guanidine Modification of Phosphate Residues on the Structure and Hybridization of Oligodeoxyribonucleotides,The Journal of Physical Chemistry B

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Effects of Phosphoryl Guanidine Modification of Phosphate Residues on the Structure and Hybridization of Oligodeoxyribonucleotides
The Journal of Physical Chemistry B ( IF 2.8 ) Pub Date : 2021-03-16 , DOI: 10.1021/acs.jpcb.0c10214
Victor M. Golyshev _{1,

2} , Dmitrii V. Pyshnyi _{1,

2} , Alexander A. Lomzov _{1,

2}

Affiliation

Phosphoryl guanidine oligonucleotides (PGOs) are promising tools for biological research and development of biosensors and therapeutics. We performed structural and hybridization analyses of octa-, deca-, and dodecamers with all phosphate residues modified by 1,3-dimethylimidazolidine-2-imine moieties. Similarity of the B-form double helix between native and modified duplexes was noted. In PGO duplexes, we detected a decrease in the proportion of C2′-endo and an increased proportion of C1′-exo sugar conformations of the modified chain. Applicability of the two-state model to denaturation transition of all studied duplexes was proved for the first time. Sequence-dependent effects of this modification on hybridization properties were observed. The thermal stability of PGO complexes is almost native at 100 mM NaCl and slightly increases with decreasing ionic strength. An increase in water activity and dramatic changes in interaction with cations and in solvation of PGOs and their duplexes were noted, resulting in slight elevation of the melting temperature after an ionic-strength decrease from 1 M NaCl down to deionized water. Decreased binding of sodium ions and decreased water solvation were documented for PGOs and their duplexes. In contrast to DNA, the PGO duplex formation leads to a release of several cations. The water shell is significantly more disordered near PGOs and their complexes. Nevertheless, changes in solvation during the formation of native and PGO complexes are similar and indicate that it is possible to develop models for predictive calculations of the thermodynamic properties of phosphoryl guanidine oligomers. Our results may help devise an approach for the rational design of PGOs as novel improved molecular probes and tools for many modern methods involving oligonucleotides.

中文翻译：

磷酸残基的磷酸胍修饰对寡脱氧核糖核苷酸结构和杂交的影响

磷酸胍胍寡核苷酸（PGO）是用于生物传感器和治疗剂的生物学研究和开发的有前途的工具。我们对八-，十-和十二聚体进行了结构和杂交分析，所有磷酸酯残基均被1,3-二甲基咪唑烷-2-亚胺部分修饰。注意到天然双链和修饰双链之间的B型双螺旋相似。在PGO双链体中，我们检测到修饰链的C2'-内切糖构象比例降低，而C1'-外切糖构象比例升高。首次证明了二态模型对所有研究的双链体的变性转变的适用性。观察到该修饰对杂交性质的序列依赖性作用。PGO配合物的热稳定性在100 mM NaCl时几乎是固有的，并且随着离子强度的降低而略有增加。注意到水活度的增加以及与阳离子的相互作用以及PGO及其双链体的溶剂化的剧烈变化，导致离子强度从1 M NaCl降至去离子水后，熔融温度略有升高。PGO及其双链体的钠离子结合力降低，水溶剂化降低。与DNA相反，PGO双链体的形成导致几种阳离子的释放。在PGO及其复合物附近，水壳的混乱状况更加明显。尽管如此，天然和PGO配合物形成过程中溶剂化的变化是相似的，这表明有可能开发用于预测计算磷酰基胍低聚物热力学性质的模型。我们的结果可能有助于设计一种合理设计PGO的方法，作为针对涉及寡核苷酸的许多现代方法的新型改良分子探针和工具。

更新日期：2021-03-25

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