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Advisor(s)
Abstract(s)
Thrombomodulin (TM) is an endothelial cell membrane protein that acts as a major cofactor in the protein C anticoagulant pathway. The EGF-like domains 4-6 of TM (TM456) are essential for PC activation. In this study, we proposed a liposomal recombinant TM conjugate to mimic the membrane TM structure and its anticoagulant activity. First, a DSPE-PEG2000-TM456 was successfully synthesized by site-specific conjugation of azido-TM456 with DSPE-PEG2000-DBCO via copper-free click chemistry quantitatively. Then, liposome-TM456 was fabricated via direct liposome formation with the DSPE-PEG2000-TM456 and other lipids. This liposomal formulation of TM456 retained protein C activation activity as that of TM456. Also, liposome-TM456 was much more stable and had a longer plasma half-life than TM456 and DSPE-PEG2000-TM456, respectively. Moreover, liposome-TM456 showed in vivo anticoagulant effect by decreasing the mortality from 80% to 20% in a thrombin-induced thromboembolism mouse model. The reported liposome-TM456 conjugate mimics the endothelial TM anticoagulation activity and may serve as an effective anticoagulant agent candidate for future development.
Description
Keywords
High pressure Biopreservation Listeria innocua Pediococcus acidilactici Bacteriocin Meat sausage
Pedagogical Context
Citation
Castro, S. M., Kolomeytseva, M., Casquete, R., Silva, J., Queiros, R., Saraiva, J. A., Teixeira, P. (2017). Biopreservation strategies in combination with mild high pressure treatments in traditional portuguese ready-to-eat meat sausage. Food Bioscience, 19, 65-72
Publisher
Elsevier