Dr Francisco Rivero Crespo F.Rivero-Crespo@hull.ac.uk
Reader in Biomedical Science
TARGETING THE MYOSIN LIGHT CHAIN PHOSPHATASE WITH PEPTIDE DISRUPTORS: A NOVEL ANTIPLATELET THERAPEUTIC APPROACH
People Involved
Dr Simon Calaminus S.Calaminus@hull.ac.uk
Professor Steve Archibald S.J.Archibald@hull.ac.uk
Professor in Molecular Imaging
Project Description
Platelet activation and thrombus formation play key roles in the pathogenesis of ischaemic cardiovascular diseases, one of the major causes of death in the UK. Many antiplatelet agents have been developed to manage these conditions; however, they are associated with a high risk of bleeding. This justifies the need to find new targets for antiplatelet drugs that effectively inhibit thrombosis while maintaining haemostasis. Actomyosin-driven contraction is a crucial process for effective platelet adhesion, spreading and aggregation at the sites of vascular damage and for thrombus formation and consolidation. The myosin light chain phosphatase (MLCP) is a key modulator of this process. We have gathered data demonstrating a novel interaction of the targeting subunit of MLCP with the regulatory subunits of protein kinase A (PKA), one of the principal inhibitors of platelet function. Our pilot data show that disrupting this interaction prevents platelets from adhering, spreading and aggregating. Based on our pilot data we propose the development and functional testing of peptides that disrupt the interaction of MLCP and PKA as a novel therapeutic approach for the prevention and management of cardiovascular conditions associated to thrombus formation.
| Status | Project Live |
|---|---|
| Funder(s) | British Heart Foundation |
| Value | £110,680.00 |
| Project Dates | Jul 3, 2023 - Jul 2, 2026 |
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