کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4753232 | 1416549 | 2017 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Recombinant and chemo-/bio-orthogonal synthesis of liposomal thrombomodulin and its antithrombotic activity
ترجمه فارسی عنوان
سنتز بازتوانی و شیمیایی / بیوالستوگونال ترومبومودولین لیپوزومی و فعالیت آنتی ترومبوتیک آن
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی شیمی
بیو مهندسی (مهندسی زیستی)
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Bioscience and Bioengineering - Volume 124, Issue 4, October 2017, Pages 445-451
Journal: Journal of Bioscience and Bioengineering - Volume 124, Issue 4, October 2017, Pages 445-451
نویسندگان
Lin Wang, Rui Jiang, Yang Liu, Maosheng Cheng, Qingyu Wu, Xue-Long Sun,