Reaction of cellular thiols with the 1, 2-dithiolan-3-one 1-oxide moiety of leinamycin triggers the generation of DNA-damaging reactive intermediates. Studies with small, synthetic analogues of leinamycin reveal that the macrocyclic portion of the natural product imparts remarkable hydrolytic stability to the 1, 2-dithiolan-3-one 1-oxide heterocycle without substantially compromising its thiol-sensing property.
