UIC 2018-074 and UIC 2020-020- Novel peptides inhibiting cell-cell aggregation and vascular occlusion in thromboinflammatory diseases

Platelet-released PDI promotes the ligand-binding function of glycoprotein Ibα (GPIbα) and induces platelet-neutrophil interactions and vascular occlusion in thromboinflammatory conditions. Extracellular PDI is crucial for platelet thrombus formation in arterial thrombosis and neutrophil recruitment in vascular inflammation. However, the development of specific PDI inhibitors is challenging because of their selectivity over 21 PDI family member thiol isomerases and potential for complications including off-target effects, cell-permeability, and perturbed hemostatic function. UIC has as developed novel antithromboinflammatory peptides and small molecules that specifically block the PDI-GPIbα signaling axis. Early studies provide evidence that specific inhibition of PDI-GPIbα signaling will be a safer and more effective therapeutic strategy for treating thromboinflammatory disease. Our data demonstrates that blocking PDI-GPIbα signaling: Reduces binding of activated αMβ2 integrin to GPIbα on the platelet surface to inhibit GPIbα-mediated platelet function and abolish platelet-neutrophil interactions. Significantly improves blood flow rates in microvessels under thromboinflammatory conditions with reduced risk of bleeding compared to conventional PDI and GPIbα inhibitors. Veronica Haywood vhaywo2@uic.otm.edu 312-996-4865