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Smart thrombosis inhibitors without bleeding side effects via charge tunable ligand design

Medicine and Health

Smart thrombosis inhibitors without bleeding side effects via charge tunable ligand design

C. C. La, S. A. Smith, et al.

This groundbreaking research introduces macromolecular polyanion inhibitors (MPIs) that neutralize polyphosphate, a key player in thrombosis. Unlike traditional anticoagulants that pose bleeding risks, these innovative MPIs show promise in preventing thrombosis without such complications. This work was conducted by authors from leading institutions, paving the way for safer therapeutic options.

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Playback language: English
Abstract
Current thrombosis prevention treatments, anticoagulants, and platelet antagonists, have a persistent risk of bleeding. This research introduces macromolecular polyanion inhibitors (MPIs) to neutralize polyphosphate (polyP), a potent procoagulant. MPIs exhibit low charge density at physiological pH but increase charge upon polyP binding, enhancing activity and selectivity. Lead MPIs demonstrated antithrombotic activity in mouse models without bleeding and were well-tolerated, suggesting a potential solution for thrombosis prevention without the bleeding risk associated with current therapies.
Publisher
Nature Communications
Published On
Apr 26, 2023
Authors
Chanel C. La, Stephanie A. Smith, Sreeparna Vappala, Reheman Adili, Catherine E. Luke, Srinivas Abbina, Haiming D. Luo, Irina Chafeeva, Matthew Drayton, Louise A. Creagh, Maria de Guadalupe Jaraquemada-Peláez, Nicole Rhoads, Manu Thomas Kalathottukaren, Peter K. Henke, Suzana K. Straus, Caigan Du, Edward M. Conway, Michael Holinstat, Charles A. Haynes, James H. Morrissey, Jayachandran N. Kizhakkedathu
Tags
thrombosis prevention
macromolecular polyanion inhibitors
polyphosphate
antithrombotic activity
bleeding risk
anticoagulants
platelet antagonists

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