Skip to main content
Open Access Publications from the University of California

UC San Diego

UC San Diego Previously Published Works bannerUC San Diego

Hydrolytic fitness of N‐glycosyl bonds: comparing the deglycosylation kinetics of modified, alternative, and native nucleosides

Published Web Location

Nature's selection of the contemporary nucleobases in RNA and DNA continues to intrigue the origin of life community. While the prebiotic synthesis of the N-glycosyl bond has historically been a central area of investigation, variations in hydrolytic stabilities among the N-glycosyl bonds may have presented an additional selection pressure that contributed to nucleobase and nucleoside evolution. To experimentally probe this hypothesis, a systematic kinetic analysis of the hydrolytic deglycosylation reactions of modified, alternative and native nucleosides was undertaken. Rate constants were measured as a function of temperature (at pH 1) to produce Arrhenius and Eyring plots for extrapolation to 37°C and determination of thermodynamic activation parameters. Rate enhancements based on the differences in reaction rates of deoxyribo- and ribo-glycosidic bonds were found to vary under the same conditions. Rate constants of deoxynucleosides were also measured across the pH range of 1 - 3 (at 50°C), which highlighted how simple changes to the heterocycle alone can lead to significant variation in deglycosylation rates. The contemporary nucleosides exhibited the slowest deglycosylation rates in comparison to the non-native/alternative nucleosides, which we suggest as experimental support for nature's selection of the fittest N-glycosyl bonds.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View