The majority of HO� attacks toward the sugar unit of DNA occurs at H5' with the formation of C5' radical, that gives an intramolecular attack to the C8 position of the purine base, generating a unique cyclic base-sugar adduct (purine 5',8-cyclo-2'-deoxynucleosides). These tandem-type lesions are observed among the DNA modifications and have also been identified in mammalian cellular DNA in vivo. Inspired by the mode of formation of these lesions, the synthetic approach to the full library of purine 5',8-cyclo-2'-deoxynucleosides has been thoroughly investigated by radical cascade protocols. In particular, the diastereomeric forms (5'R and 5'S) of 5',8-cdAdo and 5',8-cdGuo have been synthesized and fully characterized, as well as their corresponding phosphoramidates. This facilitates the quantitative determination of these lesions in biological samples as biomarker of free radical damage and the preparation of modified oligonucleotides for biochemical/biophysical studies related to specific diseases and impairment of enzymatic repair.

Bio-inspired synthetic strategies of purine 5',8-cyclonucleoside derivatives

244th National Meeting (2012)

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