Photoreaction of Thymidine with Alkylamines. Application to Selective Removal of Thymine from DNA

Article abstract of DOI:10.1021/ja00342a052

A new type of photoreaction between thymidine (Thd) and alkylamines has been described.Irradiation of Thd and methylamine in NaHCO3 aqueous solution at 0 deg C provided ring-opened adduct 15 quantitatively, which on subsequent heating gave 1-methylthymine (8).High selectivity toward Thd has been observed when the photoreaction of a mixture of dAdo, dGyd, dGuo, and Thd with methylamine was carried out at 0 deg C in the presence of diazabicyclo<2.2.2>octane (0.2 mM), and then the photolysate was kept at 20 deg C after irradiation.Irradiation of calf thymus DNA and methylamine under the specified conditions followed by heating at 70 deg C led to the efficient release of 8 from DNA.The extent of DNA modification is readily determined by the absorbance change at 300 nm, which corresponds to the amount of the ring-opened adduct between methylamine and thymine in DNA.Model experiments using thymidylyl(3'-5')-2'-deoxyadenosine demonstrate that the 3'-5' phosphodiester linkage is cleaved efficiently in this photoreaction.The present results indicate the irradiation of DNA with methylamine induces an exceedingly facile removal of thymine from DNA with the strand cleavage at the reacting thymine, providing a convenient and potentially useful method for thymine selective modification of DNA.