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一种针对血管性血友病因子A2结构域的新型单克隆抗体可减少其被ADAMTS13的切割。

A novel monoclonal antibody against the von Willebrand Factor A2 domain reduces its cleavage by ADAMTS13.

作者信息

Zhang Lulu, Su Jian, Shen Fei, Ma Zhenni, Zhao Yiming, Xia Lijun, Ruan Changgeng

机构信息

Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China.

出版信息

J Hematol Oncol. 2017 Feb 6;10(1):42. doi: 10.1186/s13045-017-0407-1.

Abstract

We developed a novel murine monoclonal antibody (mAb) against the C-terminal α-helix of the human von Willebrand factor A2, designated SZ-179. We showed that SZ-179 inhibited the interactions between VWF and ADAMTS13 and prevented the degradation of high molecular weight VWF multimers. Importantly, SZ-179 reduced the proteolysis of VWF-R1597W mutant by rADAMTS13 dose-dependently under native conditions. Our findings reveal a potential therapeutic target for bleeding disorders.

摘要

我们研发了一种针对人血管性血友病因子A2 C末端α螺旋的新型鼠单克隆抗体(mAb),命名为SZ-179。我们发现SZ-179可抑制血管性血友病因子(VWF)与ADAMTS13之间的相互作用,并防止高分子量VWF多聚体的降解。重要的是,在天然条件下,SZ-179可剂量依赖性地减少rADAMTS13对VWF-R1597W突变体的蛋白水解作用。我们的研究结果揭示了出血性疾病的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f797/5292787/6616597f4a38/13045_2017_407_Fig1_HTML.jpg

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