Researchers demonstrate novel method for studying the DNA binding of small molecules
Northeastern University professor Mark C. Williams and graduate student Ioana Vladescu have discovered a novel method for studying the DNA binding of small molecules with unprecedented accuracy. Their paper, titled “Quantifying force-dependent and zero-force DNA intercalation by single-molecule stretching,” has been published in the June 2007 issue of the prestigious Nature Methods.
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!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
Nano-hologram paves way for integration of 3-D holography into everyday electronics
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...