New molecule has potential to help treat genetic diseases and HIV

Feb 13, 2012
Chemists at The University of Texas at Austin have synthesized a molecule that can entangle itself in a specific sequence of DNA and stay attached for 16 days, longer than any other molecule reported.

(PhysOrg.com) -- Chemists at The University of Texas at Austin have created a molecule that's so good at tangling itself inside the double helix of a DNA sequence that it can stay there for up to 16 days before the DNA liberates itself, much longer than any other molecule reported.

It's an important step along the path to someday creating drugs that can go after rogue DNA directly. Such drugs would be revolutionary in the treatment of genetic diseases, cancer or retroviruses such as HIV, which incorporate directly into the body's DNA.

"If you think of DNA as a spiral staircase," says Brent Iverson, professor of chemistry and chair of the department of chemistry and biochemistry, "imagine sliding something between the steps. That's what our molecule does. It can be visualized as binding to DNA in the same way a snake might climb a ladder. It goes back and forth through the central staircase with sections of it between the steps. Once in, it takes a long time to get loose."

Iverson says the goal is to be able to directly turn on or off a particular sequence of .

"Take HIV, for example," he says. "We want to be able to track it to wherever it is in the chromosome and just sit on it and keep it quiet. Right now we treat HIV at a much later stage with drugs such as the , but at the end of the day, the HIV DNA is still there. This would be a way to silence that stuff at its source."

Iverson, whose results were published in September in Nature Chemistry, strongly cautions that there are numerous obstacles to overcome before such treatments could become available.

The hypothetical drug would have to be able to get into cells and hunt down a long and specific DNA sequence in the right region of our . It would have to be able to bind to that sequence and stay there long enough to be therapeutically meaningful.

"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 that bind to longer and more biologically significant .

"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."

Explore further: Four new dragon millipedes found in China

Related Stories

DNA falls apart when you pull it

May 20, 2011

DNA falls apart when you pull it with a tiny force: the two strands that constitute a DNA molecule disconnect. Peter Gross of VU University Amsterdam has shown this in his PhD research project. With this research, ...

Exploring the 'last frontier' of our genome

Sep 23, 2011

The human genome first appeared in print in 2001. But scientists aren’t done yet. There’s part of our DNA that geneticists have yet to assemble a sequence for: the centromeres.

Models begin to unravel how single DNA strands combine

Oct 05, 2009

(PhysOrg.com) -- Using computer simulations, a team of University of Wisconsin-Madison researchers has identified some of the pathways through which single complementary strands of DNA interact and combine to form the double ...

Recommended for you

Science casts light on sex in the orchard

18 hours ago

Persimmons are among the small club of plants with separate sexes—individual trees are either male or female. Now scientists at the University of California, Davis, and Kyoto University in Japan have discovered ...

Four new dragon millipedes found in China

20 hours ago

A team of speleobiologists from the South China Agriculture University and the Russian Academy of Sciences have described four new species of the dragon millipedes from southern China, two of which seem to ...

Scientist creates automatic birdsong recognition app

23 hours ago

Dr Dan Stowell, an EPSRC Research Fellow in QMUL's School of Electrical Engineering and Computer Science, has used a grant from Queen Mary Innovation to develop a prototype for an app that turns his research ...

New research reveals fish are smarter than we thought

23 hours ago

(Phys.org) —A new study from researchers in our Department of Psychology with colleagues at Queen Mary University of London has reported the first evidence that fish are able to process multiple objects ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.