Poster # 2
HIGH THROUGHPUT SCREENING ASSAY TO IDENTIFY SMALL MOLECULE INHIBITORS OF Gα12 /α-SNAP-DEPENDENT vWF SECRETION
Co-authors: Sweta Misra, UIC: Hyun Lee, UIC; Malaika D. Argade, UIC; Kiira Ratia, UIC; Richard D. Minshall, UIC; Laura J. Bloem, UIC
PRESENTER’S INFO:
Name: Laura Bloem
Email: lbloem@uic.edu
Title: Faculty
Affiliation: University of Illinois Chicago
Department: Pharmaceutical Sciences
Advisor: Dr. Richard D. Minshall
Advisor’s Email: rminsh@uic.edu
Abstract:
Inflammatory states such as cancer, Type-2 Diabetes and severe infections lead to cardiovascular complications with greater risk of developing life-threatening blood clots. These pathological conditions are associated with elevated blood pressure and pro-inflammatory cytokine levels leading to endothelial cell activation and secretion of von Willebrand Factor (vWF), a major factor facilitating platelet adhesion and subsequent thrombus formation. Previous studies demonstrated G12 interacts with α-SNAP (soluble N-ethylmaleimide sensitive-factor attachment protein) and is required for α-SNAP dependent vWF secretion. A peptide antagonist (SBD6) of the Gα12/α-SNAP interaction was designed from the Gα12 amino terminal domain. A cell permeable myristoylated SBD6 blocked both basal and thrombin induced vWF secretion in human endothelial cell cultures and reduced thrombosis in an animal model of sepsis. Here we report the design, development, execution and results of a high throughput screen (HTS) using the Amplified Luminescent Proximity Homogeneous Assay (AlphaLISA®) format to identify small molecule inhibitors of Gα12/α-SNAP interaction for the development of anti-thrombotic therapeutics.
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