Selective Radiation-Induced Generation of 2-Deoxyribonolactone Lesions in DNA Mediated by Aromatic Iodonium Derivatives

Abstract

2-Deoxyribonolactone lesions were identified as major products of radiation damage to DNA mediated by o,o'-diphenyleneiodonium cations in a hydroxyl radical-scavenging environment. The highest selectivity toward deoxyribonolactone formation (up to 86% of all sugar-phosphate damages) and the overall reaction efficiency (up to 40% of all radiation-generated intermediates converted into products) was displayed by derivatives with positively charged (2-aminoethylthio)acetylamino and (2-aminoethylamino)acetylamino side chains. The reaction can be useful for random single-step incorporation of deoxyribonolactone lesions into single- and double-stranded oligonucleotides and highly polymerized DNA directly in commonly used buffers (PBS, phosphate, Tris-HCl, etc.) at room temperature. In combination with HPLC separation, this technique can serve as a source of short (<6 mer) sequences containing deoxyribonolactone lesions at known positions.