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A Synthetic Oligonucleotide Model for Evaluating the Oxidation and Crosslinking Propensities of Natural Furan‐Modified DNA
Author(s) -
Carrette Lieselot L. G.,
Madder Annemieke
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201300612
Subject(s) - furan , oligonucleotide , moiety , chemistry , dna , combinatorial chemistry , dna damage , natural product , organic chemistry , biochemistry
We have previously developed a crosslinking methodology for oligonucleotides based on the incorporation of furan moieties, which can be selectively oxidised to reactive intermediates that will quickly react with the opposite bases in DNA, forming toxic interstrand crosslinks (ICLs). Furan moieties also occur in natural DNA, as a result of oxidative stress. Moreover, the furan‐containing degradation product of this modified DNA—kinetin—has been found to display beneficial anti‐ageing effects. To investigate the apparent discrepancy between the effects of the synthetic and the natural furan modifications in DNA, a quick and easy postsynthetic method providing access to the natural modification in short synthetic oligonucleotides was developed. On checking for potential crosslinking propensity, we found that the furan moiety does indeed undergo oxidation, in this way functioning as an important scavenger for oxidative stress. The reactive intermediate, however, was shown to degrade without producing toxic crosslinked products.