The genetic material of all living organisms reacts with free radicals, which leads to modification of gene composition and structure and possibly of its expression. In particular, hydroxyl radicals (HO?) formed both by internal (oxidative cellular metabolism) and external factors (chemicals, sunlight, ?-irradiation) represent one of the most effective species.1,2 Single or multiple lesions may occur in DNA and base excision repair (BER) and nucleotide excision repair (NER) mechanisms provide enzymatic pathways to remove these lesions for the maintenance of genome integrity.3 Chemical studies play a central role for enabling the identification and quantitation of the main classes of DNA oxidative damages.4 Among others, purine 5',8-cyclo-2'-deoxynucleosides are an important class of lesions caused by ionizing radiations and their potential to become free radical stress markers related to the development of pathologies is a matter of investigation.5 All four diastereomers 5',8-cdAdo (1 and 2) and 5',8-cdGuo (3 and 4) were synthesized as phosphoramidites. A variety of oligonucleotides, containing 5',8-cyclopurine were designed and synthesized in order to investigate: (i) synthesis efficiency and characterizations of oligonucleotides; (ii) physico-chemical properties of ds-DNA; (iii) the relative DNA-repair efficiency. 1C. C. Winterbourn, Biological Chemistry of Reactive Oxygen Species in Encyclopedia of Radicals in Chemistry, Biology and Materials, eds C. Chatgilialoglu and A. Studer, John Wiley & Sons Ltd, Chichester, UK, 2012, pp 1259-1281. 2N. E. Geacintov and V. Shafirovich, Reactions of Small Reactive Species with DNA in Encyclopedia of Radicals in Chemistry, Biology and Materials, eds C. Chatgilialoglu and A. Studer, John Wiley & Sons Ltd, Chichester, UK, 2012, pp 1283-1317. 3J. C. Delaney and J. M. Essigmann, Chem. Res. Toxicol., 2008, 21, 232. 4.J. Cadet, T. Douki and J-L.Ravanat, Acc. Chem. Res., 2008, 41, 1075. J. R. Wagner and J. Cadet, Acc. Chem. Res., 2010, 43, 564. 5C. Chatgilialoglu, C. Ferreri and M. A. Terzidis, Chem. Soc. Rev., 2011, 40, 1368. 6J. Wang, C. L. Clauson, P. D. Robbins, L. J. Niedernhofer and Y. Wang, Aging Cell, 2012, 11, 714. 7C. You, X. Dai, B. Yuan, J. Wang, J. Wang, P. J. Brooks, L. J. Niedernhofer and Y. Wang, Nat. Chem. Biol., 2012, 10, 817.
Synthesis and properties of oligonucleotides containing purine 5',8-cyclo-2'-deoxynucleoside lesions as models of free radical DNA damage
Annalisa Masi;Chryssostomos Chatgilialoglu
2013
Abstract
The genetic material of all living organisms reacts with free radicals, which leads to modification of gene composition and structure and possibly of its expression. In particular, hydroxyl radicals (HO?) formed both by internal (oxidative cellular metabolism) and external factors (chemicals, sunlight, ?-irradiation) represent one of the most effective species.1,2 Single or multiple lesions may occur in DNA and base excision repair (BER) and nucleotide excision repair (NER) mechanisms provide enzymatic pathways to remove these lesions for the maintenance of genome integrity.3 Chemical studies play a central role for enabling the identification and quantitation of the main classes of DNA oxidative damages.4 Among others, purine 5',8-cyclo-2'-deoxynucleosides are an important class of lesions caused by ionizing radiations and their potential to become free radical stress markers related to the development of pathologies is a matter of investigation.5 All four diastereomers 5',8-cdAdo (1 and 2) and 5',8-cdGuo (3 and 4) were synthesized as phosphoramidites. A variety of oligonucleotides, containing 5',8-cyclopurine were designed and synthesized in order to investigate: (i) synthesis efficiency and characterizations of oligonucleotides; (ii) physico-chemical properties of ds-DNA; (iii) the relative DNA-repair efficiency. 1C. C. Winterbourn, Biological Chemistry of Reactive Oxygen Species in Encyclopedia of Radicals in Chemistry, Biology and Materials, eds C. Chatgilialoglu and A. Studer, John Wiley & Sons Ltd, Chichester, UK, 2012, pp 1259-1281. 2N. E. Geacintov and V. Shafirovich, Reactions of Small Reactive Species with DNA in Encyclopedia of Radicals in Chemistry, Biology and Materials, eds C. Chatgilialoglu and A. Studer, John Wiley & Sons Ltd, Chichester, UK, 2012, pp 1283-1317. 3J. C. Delaney and J. M. Essigmann, Chem. Res. Toxicol., 2008, 21, 232. 4.J. Cadet, T. Douki and J-L.Ravanat, Acc. Chem. Res., 2008, 41, 1075. J. R. Wagner and J. Cadet, Acc. Chem. Res., 2010, 43, 564. 5C. Chatgilialoglu, C. Ferreri and M. A. Terzidis, Chem. Soc. Rev., 2011, 40, 1368. 6J. Wang, C. L. Clauson, P. D. Robbins, L. J. Niedernhofer and Y. Wang, Aging Cell, 2012, 11, 714. 7C. You, X. Dai, B. Yuan, J. Wang, J. Wang, P. J. Brooks, L. J. Niedernhofer and Y. Wang, Nat. Chem. Biol., 2012, 10, 817.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
