Experimental and theoretical rationalization for the base pairing abilities of inosine, guanosine, adenosine, and their corresponding8‐oxo ‐7,8‐dihydropurine, and8‐bromopurine analogues within A‐form duplexes ofRNA
| Autor: | Chou-Hsun Yang, Marino J. E. Resendiz, Kazuki Hincks, Haobin Wang, Austin Skinner |
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| Rok vydání: | 2020 |
| Předmět: |
RNA oxidation
Adenosine Guanine Pyrimidine Base pair Stereochemistry Biophysics Guanosine 8-oxoG 8-oxoA 010402 general chemistry 01 natural sciences Biochemistry Article Nucleobase Biomaterials chemistry.chemical_compound medicine Nucleotide inosine within duplexes of RNA Nucleic acid structure Inosine Base Pairing chemistry.chemical_classification Models Genetic Molecular Structure 010405 organic chemistry Organic Chemistry RNA Hydrogen Bonding General Medicine 0104 chemical sciences Models Chemical chemistry 8-oxoI Nucleic Acid Conformation Thermodynamics thermal stability of modified duplexes of RNA medicine.drug |
| Zdroj: | Biopolymers |
| ISSN: | 1097-0282 0006-3525 |
| Popis: | Inosine is an important RNA modification, furthermore RNA oxidation has gained interest due, in part, to its potential role in the development/progression of disease as well as on its impact on RNA structure and function. In this report we established the base pairing abilities of purine nucleobases G, I, A, as well as their corresponding, 8-oxo-7,8-dihydropurine (common products of oxidation at the C8-position of purines), and 8-bromopurine (as probes to explore conformational changes), derivatives, namely 8-oxoG, 8-oxoI, 8-oxoA, 8-BrG, and 8-BrI. Dodecamers of RNA were obtained using standard phosphoramidite chemistry via solid-phase synthesis, and used as models to establish the impact that each of these nucleobases have on the thermal stability of duplexes, when base pairing to canonical and noncanonical nucleobases. Thermal stabilities were obtained from thermal denaturation transition (Tm ) measurements, via circular dichroism (CD). The results were then rationalized using models of base pairs between two monomers, via density functional theory (DFT), that allowed us to better understand potential contributions from H-bonding patterns arising from distinct conformations. Overall, some of the important results indicate that: (a) an anti-I:syn-A base pair provides thermal stability, due to the absence of the exocyclic amine; (b) 8-oxoG base pairs like U, and does not induce destabilization within the duplex when compared to the pyrimidine ring; (c) a U:G wobble-pair is only stabilized by G; and (d) 8-oxoA displays an inherited base pairing promiscuity in this sequence context. Gaining a better understanding of how this oxidatively generated lesions potentially base pair with other nucleobases will be useful to predict various biological outcomes, as well as in the design of biomaterials and/or nucleotide derivatives with biological potential. |
| Databáze: | OpenAIRE |
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