Year: 2016
Type: dissertation
Abstract: Cystic fibrosis is the most common genetic disease affecting the Canadian population. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, and there is currently no cure. In 2012, VX-770 became the first FDA approved drug targeting the genetic defects of CF; its binding site and mechanism of action are currently unknown. In the present study, we studied the structure-function relationship of VX-770. We determined the structural components that are critical for activity and identified a position on the structure that could be modified without compromising its effects. These findings led to the generation of VX-770-Biotin and VX-770-Rhodamine. Subsequent testing of the two molecular probes suggests that they both retain properties of the parental drug VX-770. Hence, VX-770-Biotin and VX-770-Rhodamine may be used to provide further insight into the VX-770 binding site and mechanism of action, enabling the design of more effective drugs for CF therapy.
Source: TSpace (University of Toronto)
Author: Maurita Hung
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2900746726