Genomics-based drug design targets the AT-rich malaria parasite: implications for antiparasite chemotherapy

Evaluation of: Woynarowski JM, Krugliak M, Ginsburg H: Pharmacogenomic analyses of targeting the AT-rich malaria parasite genome with AT-specific alkylating drugs. Mol. Biochem. Parasitol. 154(1), 70-81 (2007) [1] . The sequencing of the malaria genome sought to expose the parasite's ability to cause disease and identify new targets for antimalarial drugs and vaccines. In this study, the authors discovered how malaria genomic DNA, which is unusually rich in adenine and thymine nucleotides, is intrinsically a target for a selective class of compounds. AT-specific DNA-binding agents have previously been shown to have potent antimalarial activity in vitro. The authors used high-resolution bioinformatic tools to explore the genomic basis for this drug susceptibility, first at the level of individual DNA-binding sites, then expanding to the entire genomic context of each malaria chromosome. Their findings revealed a nonrandom distribution and organization of drug-binding sites that can be further exploited to target these AT sequences. Based on these findings, comparative bioinformatics analyses with other parasite genomes may lead to the identification of new target organisms for these AT-specific drugs and have wide implications for the treatment of human and animal parasitic diseases.