Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


VCU researchers design new receptor and enhance bioassay to advance drug discovery process


Virginia Commonwealth University chemists have created a new molecular receptor for a fluorescent dye used to track a drug candidate’s activity inside cell membranes.

These findings may help researchers more efficiently design, evaluate and test new drugs like antibiotics and therapeutics for genetic diseases, such as cystic fibrosis and Bartter’s syndrome, because they will know precisely where the drug is acting inside a cell.

According to the study in the Journal of the American Chemical Society, published online on September 27, researchers designed and synthesized a new cyclen-based receptor, and demonstrated its ability to strongly bind the fluorescent dye, pyranine, under near-physiological conditions. Furthermore, researchers were able to improve upon the currently applied membrane leakage assay used to evaluate specific properties of a developmental drug compound. Assays are used to help develop safer drugs by evaluating properties of absorption, distribution and metabolism.

“There is a growing need for the development of assays to rapidly assess the activity of developmental drug compounds under near-physiological conditions,” said Vladimir Sidorov, Ph.D., a professor of organic chemistry at VCU and lead investigator of this study. “Therefore, we wanted to improve on the existing membrane leakage assay.

“The high affinity of this receptor to pyranine, its impermeability to the lipid bilayer membrane and fast kinetics of binding were used as a basis for the new membrane-leakage assay,” he said.

According to Sidorov, the membrane leakage assay is compatible with a second type of assay that monitors the ionophoretic activity of the drug candidate in the cell model. Ionophoretic activity is the ability of compound to transport ions across biological membranes. Using the assays together allows researchers to distinguish between selective ion transport and formation of large pores perturbing the integrity of cell membranes within a single set of experiments.

The new receptor is ideal because it selectively binds to pyranine, he said. Pyranine does not penetrate the lipid membrane of the cell, and therefore could provide the basis for a membrane leakage assay.

“The receptor we have created requires an extremely low concentration for the dye to be bound,” said Sidorov. In current assays, researchers use high concentrations of probe DPX, a dicationic organic compound used to quench the fluorescence of pyranine. The affinity and specificity of DPX to pyranine is low.

“The problem with using high concentrations of a probe is that it becomes difficult to detect where the activity is actually occurring and difficult to determine the impact it may have on the membrane or cell itself,” he said.

“The therapeutic properties and side effects produced by the wide variety of drugs are tightly associated with their function in cell membranes,” Sidorov said. “Therefore, the methods allowing accurate assessment of these membrane functions have crucial importance for the development of safer and more efficient drugs.”

The assay described in this study allows researchers to assess the mechanism of ion transport, which can detect potential therapeutics against cystic fibrosis and Bartter’s syndrome. Both are inherited genetic diseases associated with the malfunction of natural proteins transporting chloride anions across cell membranes. The synthetic compounds capable of such transport can function in place of compromised proteins and therefore, one day, treat the diseases. Sidorov and his colleagues are also currently investigating the development of such Cl- transporters.

Bartter’s syndrome causes the kidneys to excrete excessive amounts of electrolytes such as potassium, sodium and chloride, resulting in electrolyte abnormalities. Two potential outcomes of Bartter’s syndrome are kidney failure and inner-ear defects resulting in deafness.

This work was supported by grants from the National Science Foundation, VCU startup fund and Jeffress Memorial Trust.

Sathya Achia-Abraham | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Strong, steady forces at work during cell division
20.10.2016 | University of Massachusetts at Amherst

nachricht Disturbance wanted
20.10.2016 | Max Delbrück Center for Molecular Medicine in the Helmholtz Association

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Innovative technique for shaping light could solve bandwidth crunch

20.10.2016 | Physics and Astronomy

Finding the lightest superdeformed triaxial atomic nucleus

20.10.2016 | Physics and Astronomy

NASA's MAVEN mission observes ups and downs of water escape from Mars

20.10.2016 | Physics and Astronomy

More VideoLinks >>>