Because molecules that bind through intercalation (a type of binding) may interfere with important biochemical processes in replicating cells, this method may be a useful tool for rational drug design targeting cancer, AIDS and other diseases.
“In order to develop new drugs to treat cancer and other diseases, scientists need to better understand if and how these drugs will bind to DNA,” says Williams. “This new method allows us to examine intercalation in unprecedented and exquisite detail.”
Williams and colleagues used single DNA molecule stretching to investigate DNA intercalation by ethidium and three ruthenium complexes. By measuring ligand-induced DNA elongation at different ligand concentrations, they determined the binding constant and site size as a function of force. Both quantities depend strongly on force and, in the limit of zero force, converge to the known bulk solution values, when available.
This approach allowed the team, comprised of Williams, Vladescu and Northeastern colleague Micah McCauley, along with Megan Nunez from Mt. Holyoke College, and Ioulia Rouzina from the University of Minnesota to distinguish the intercalative mode of ligand binding from other binding modes and allowed characterization of intercalation with binding constants ranging over almost six orders of magnitude, including ligands that do not intercalate under experimentally accessible bulk solution conditions. As ligand concentration increased, the DNA stretching curves saturated at the maximum amount of ligand intercalation. The results showed that the applied force partially relieves normal intercalation constraints. The team also characterized the flexibility of intercalator-saturated dsDNA for the first time.
Williams and his colleagues are continuing their research and plan to start testing actively used cancer drugs in the near-term.
Laura Shea | EurekAlert!
Helping to Transport Proteins Inside the Cell
21.11.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
UNH researchers create a more effective hydrogel for healing wounds
21.11.2018 | University of New Hampshire
Innsbruck quantum physicists have constructed a diode for magnetic fields and then tested it in the laboratory. The device, developed by the research groups led by the theorist Oriol Romero-Isart and the experimental physicist Gerhard Kirchmair, could open up a number of new applications.
Electric diodes are essential electronic components that conduct electricity in one direction but prevent conduction in the opposite one. They are found at the...
Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.
Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
21.11.2018 | Life Sciences
21.11.2018 | Power and Electrical Engineering
21.11.2018 | Life Sciences