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Drug discovery and development is an important aspect of society, saving over a million life-years. Drugs work by targeting and tightly binding to key components of a disease. But macromolecularly crowded environments within a cell can change the binding of a drug to its target. Crowding reduces the amount of unoccupied space available for the drug, limiting its movement, and effecting the speed at which it reacts. This project aims to study the effects of macromolecular crowding on drug-target binding of proflavine to calf thymus DNA and yeast tRNA with isothermal titration calorimetry and competition dialysis. We have shown that proflavine has a high binding affinity to calf thymus DNA. Proflavine also shows selective binding to calf thymus DNA over tRNA. When BSA was added as a macromolecular crowder, there was little to no effect on the binding of proflavine to calf thymus DNA or tRNA. This is just a start and we hope that the effects of macromolecular crowding on drug binding will continue to be studied.
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Freer, Abigail Kathryn, "The Effects of Macromolecular Crowding on the Thermodynamics and Selectivity of Drug Binding" (2020). Senior Projects Spring 2020. 44.
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