The anticancer agent ellipticine unwinds DNA by intercalative binding in an orientation parallel to base pairs.
Ellipticine is a natural plant product that has been found to be a powerful anticancer drug. Although still unclear, its mechanism of action is considered to be mainly based on DNA intercalation and/or the inhibition of topoisomerase II. Many experimental data suggest an intercalation based on stacking interactions along the major base-pair axis, but alternative binding modes have been proposed, in particular for ellipticine derivatives. The 1.5 A resolution structure of ellipticine complexed to a 6 bp oligonucleotide unveils its mode of binding and enables a detailed analysis of the distorting effects of the drug on the DNA.
Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Parc Científic de Barcelona, Baldiri Reixac 10-12, 08028 Barcelona, Spain. acpcri@ibmb.csic.es
Albert
A
Canals
Mònica
M
Purciolas
Joan
J
Aymamí
Miquel
M
Coll
D000970:Antineoplastic Agents / Q000737:chemistry*; D020029:Base Pairing; D018360:Crystallography, X-Ray / Q000379:methods; D004247:DNA / Q000737:chemistry*; D004611:Ellipticines / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry*
D000970:Antineoplastic Agents; D004611:Ellipticines; D007364:Intercalating Agents; C034192:ellipticine; D004247:DNA