Experimental and theoretical rationalization for the base pairing abilities of inosine, guanosine, adenosine, and their corresponding 8-oxo-7,8-dihydropurine, and 8-bromopurine analogues within A-form duplexes of RNA.
Abstract
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 tha...Continue Reading
References
Citations
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Alpha-Synuclein Aggregation (MDS)
Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.