Paper Number
PO86
Session
Poster Session
Title
Viscosity as an indicator of small molecule drug binding with DNA
Presentation Date and Time
October 12, 2022 (Wednesday) 6:30
Track / Room
Poster Session / Riverwalk A
Authors
- Ochoa, Chrystian (RheoSense Inc.)
- Elliot, Stacey (RheoSense, Inc.)
- Baek, Seonggi (RheoSense, Inc.)
Author and Affiliation Lines
Chrystian Ochoa1, Stacey Elliot2 and Seonggi Baek2
1RheoSense Inc., Chicago, IL; 2RheoSense, Inc., San Ramon, CA 94583
Speaker / Presenter
Ochoa, Chrystian
Keywords
experimental methods; bio-fluids; biomaterials; rheometry techniques
Text of Abstract
DNA is often the cellular target for binding studies with certain classes of small molecule drugs. The extent of disruption to the DNA confirmation will vary with the different binding modes which include electrostatic, external, groove, and intercalative. Intercalation is the most extreme because the drug molecules insert between DNA base pairs and lead to an elongation of the double helix. Since viscosity is sensitive to the molecular level structure, the presence of bound drug molecules can increase the viscosity of DNA in solution to varying extents depending on the binding modes present. Therefore, viscosity measurements can be complementary to other techniques such as electronic absorption spectroscopy to identify the dominant type of drug binding. We demonstrate the use of viscosity measurements to characterize the binding of the drug sumatriptan to calf thymus DNA in Tris-HCl buffer. Viscosity data is presented for solutions prepared with a fixed concentration of DNA and varying levels of sumatriptan. The rate of increase in viscosity with the drug to DNA ratio and its relevance to the dominant drug binding mode is also discussed.