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Hydrolytic fitness of N ‐glycosyl bonds: comparing the deglycosylation kinetics of modified, alternative, and native nucleosides
Author(s) -
Rios Andro C.,
Yu Hiu T.,
Tor Yitzhak
Publication year - 2015
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.3318
Subject(s) - chemistry , glycosyl , nucleobase , reaction rate constant , hydrolysis , nucleoside , kinetics , stereochemistry , glycosylation , computational chemistry , organic chemistry , dna , biochemistry , physics , quantum mechanics
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 stability 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 deoxyriboglycosidic and riboglycosidic 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 a significant variation in deglycosylation rates. The contemporary nucleosides exhibited the slowest deglycosylation rates in comparison with the nonnative/alternative nucleosides, which we suggest as experimental support for nature's selection of the fittest N ‐glycosyl bonds. Copyright © 2014 John Wiley & Sons, Ltd.