Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New molecule can tangle up DNA for more than 2 weeks

15.02.2012
Molecule is important step along the path to someday creating drugs that can go after rogue DNA directly

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.


This shows a model of the "threading tetra-intercalator" bound up in the double helix of a DNA sequence. Credit: Brent Iverson

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 viral DNA 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. Our off-rate under the conditions we used is the slowest we know of by a wide margin."

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

"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 protease inhibitors, 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 Nature Chemistry and presented this month at a colloquium at NYU, 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 genome. 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 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."

Iverson and Rhoden Smith's co-authors on the paper were Maha Zewail-Foote, a visiting scientist in Iverson's lab who's now an associate professor and chairman of chemistry at Southwestern University in Georgetown; Garen Holman, another former doctoral student of Iverson's who did most of the experimental work before obtaining his Ph.D.; and Kenneth Johnson, the Roger J. Williams Centennial Professor in Biochemistry at The University of Texas at Austin.

Daniel Oppenheimer | EurekAlert!
Further information:
http://www.utexas.edu

Further reports about: DNA DNA sequence HIV genetic disease threading tetra-intercalator

More articles from Life Sciences:

nachricht 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

nachricht Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>