Bulky DNA Adducts

As this article explains, Aristolochic acids I and II are two plant toxicants found in the Aristolochiaceae plant family. The acids poison humans by messing with DNA. Metabolic activation of the aristolochic acids leads to the formation of a cyclic N-hydroxylactam product. This product can react with the peripheral amino group of purine bases, thus generating bulky DNA adducts. Therefore, these acids are classified as mutagens and human carcinogens.

Although the AL-dG adducts would with time disappear from the DNA of laboratory animals, AL-dA lesions would still be present in the genomes of the animals. The researchers' data establish a locally perturbed double helical structure that actually accommodated the bulky adduct. The structure did this by displacing the counter residue from the bulky adducts into the major groove and stacking the ALII moiety between flanking bases. The presence of the ALII-dA perturbs the conformation of the 5'-side flanking base pair.However,  all other pairs of the duplex take on their standard conformations. Thermodynamic studies have shown that the lesion slightly decreases the energy of duplex formation in a sequence-dependent manner.