Synthesis and sequence preference of acetaldehyde-derived oligonucleotide interstrand cross-link

Acetaldehyde (AA) is mutagenic and carcinogenic. Several previously unknown AA-DNA adducts have been identified, including an interstrand cross-link, 3-(2-deoxyribos-1-yl)-5, 6,7,8-tetrahydro-8-(N2-deoxyguanosyl)-6-methylpyrimido [1, 2-a]purine-10(3H)one. This cross-link was synthesized in a double-stranded oligonucleotide appropriate for studies of mutagenicity and repair in human cells. The cross-linked oligonucleotide was characterized by MS and enzymatic hydrolysis experiments. Another oligonucleotide containing the irreversible analog of the cross-link, 1,3-bis(2x-deoxyguanos-N2-yl) butane, was also synthesized and characterized. It is being utilized as a control in the mutagenicity studies. The sequence preference for AA-derived cross-link formation was also determined. This is an abstract of a paper presented at the 228th ACS National Meeting (Philadelphia, PA 8/22-26/2004).