The antimalarial and cytotoxic drug cryptolepine intercalates into DNA at cytosine-cytosine sites.
Cryptolepine, a naturally occurring indoloquinoline alkaloid used as an antimalarial drug in Central and Western Africa, has been found to bind to DNA in a formerly unknown intercalation mode. Evidence from competition dialysis assays demonstrates that cryptolepine is able to bind CG-rich sequences containing nonalternating CC sites. Here we show that cryptolepine interacts with the CC sites of the DNA fragment d(CCTAGG)(2) in a base-stacking intercalation mode. This is the first DNA intercalator complex, from approximately 90 solved by X-ray crystallography, to bind a nonalternating (pyrimidine-pyrimidine) DNA sequence. The asymmetry of the drug induces a perfect stacking with the asymmetric site, allowing for the stability of the complex in the absence of hydrogen bonding interactions. The crystal structure of this antimalarial drug-DNA complex provides evidence for the first nonalternating intercalation and, as such, provides a basis for the design of new anticancer or antimalarial drugs.[1]References
- The antimalarial and cytotoxic drug cryptolepine intercalates into DNA at cytosine-cytosine sites. Lisgarten, J.N., Coll, M., Portugal, J., Wright, C.W., Aymami, J. Nat. Struct. Biol. (2002) [Pubmed]
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