In 37 painstaking steps, the authors of this latest report synthesized an exact mirror image of a well-known anticancer drug, daunorubicin, used to treat acute leukemias. Normally, this drug binds to B-DNA, preventing the DNA from being duplicated. As a result, it prevents cells from multiplying out of controlthe root cause of cancer. The researchers found thateven though Z-DNA is not a perfect mirror image of B-DNAthe mirror-image drug still bound specifically to left-handed Z-DNA. And in addition, it converted a mixture of B- and Z-DNA into pure Z-DNA.
In a preliminary study, the researchers then tested how poisonous the new drug wascompared with a related, right-handed compound called doxorubicinby administering it to two different cancer cell lines, one that is sensitive to drugs and one that is multidrug-resistant. On the sensitive cells, the new drug was not as effective as the right-handed drug, but it was five times better at killing the resistant cells. Although they cannot be certain, the researchers therefore suspect its potency might stem from its ability to bind to left-handed DNA. Whether drugs binding to left-handed DNA will ultimately define a new class of anticancer drugs remains to be seen, but they surely provide a tool for studying Z-DNA in the cell.