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 perturb
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Contact: Sathya Achia-Abraham
sbachia@vcu.edu
804-827-0890
Virginia Commonwealth University
29-Sep-2005