"Those are the big hurdles, but we jumped over two of them," says Iverson. "I'll give presentations in which I begin by asking: Can DNA be a highly specific drug target? When I start, a lot of the scientists in the audience think it's a ridiculous question. By the time I'm done, and I've shown them what we can do, it's not so ridiculous anymore."
In order to synthesize their binding molecule, Iverson and his colleagues begin with the base molecule naphthalenetetracarboxylic diimide (NDI). It's a molecule that Iverson's lab has been studying for more than a decade.
They then piece NDI units together like a chain of tinker toys.
"It's pretty simple for us to make," says Amy Rhoden Smith, a doctoral student in Iverson's lab and co-author on the paper. "We are able to grow the chain of NDIs from special resin beads. We run reactions right on the beads, attach pieces in the proper order and keep growing the molecules until we are ready to cleave them off. It's mostly automated at this point."
Rhoden Smith says that the modular nature of these NDI chains, and the ease of assembly, should help enormously as they work toward developing molecules that bind to longer and more biologically significant DNA sequences.
"The larger molecule is composed of little pieces that bind to short segments of DNA, kind of like the way Legos fit together," she says. "The little pieces can bind different sequences, and we can put them together in different ways. We can put the Legos in a different arrangement. Then we scan for sequences that they'll bind."
|Contact: Daniel Oppenheimer|
University of Texas at Austin