Characterization of von Willebrand Factor Interaction with Collagens in Real Time Using Surface Plasmon Resonance

2002 ◽  
Vol 30 (9) ◽  
pp. 1107-1116 ◽  
Author(s):  
Feng Li ◽  
Joel L. Moake ◽  
Larry V. McIntire
Haematologica ◽  
2019 ◽  
Vol 105 (11) ◽  
pp. 2631-2638 ◽  
Author(s):  
Kazuya Sakai ◽  
Tatsuhiko Someya ◽  
Kaori Harada ◽  
Hideo Yagi ◽  
Taei Matsui ◽  
...  

von Willebrand factor (VWF) is a blood glycoprotein that plays an important role in platelet thrombus formation through interaction between its A1 domain and platelet glycoprotein Ib. ARC1779, an aptamer to the VWF A1 domain, was evaluated in a clinical trial for acquired thrombotic thrombocytopenic purpura (aTTP). Subsequently, caplacizumab, an anti-VWF A1 domain nanobody, was approved for aTTP in Europe and the United States. We recently developed a novel DNA aptamer, TAGX-0004, to the VWF A1 domain; it contains an artificial base and demonstrates high affinity for VWF. To compare the effects of these three agents on VWF A1, their ability to inhibit ristocetin- or botrocetin-induced platelet aggregation under static conditions was analyzed, and the inhibition of thrombus formation under high shear stress was investigated in a microchip flow chamber system. In both assays, TAGX-0004 showed stronger inhibition than ARC1779, and had comparable inhibitory effects to caplacizumab. The binding sites of TAGX-0004 and ARC1779 were analyzed with surface plasmon resonance performed using alanine scanning mutagenesis of the VWF A1 domain. An electrophoretic mobility shift assay showed that R1395 and R1399 in the A1 domain bound to both aptamers. R1287, K1362, and R1392 contributed to ARC1779 binding, and F1366 was essential for TAGX-0004 binding. Surface plasmon resonance analysis of the binding sites of caplacizumab identified five amino acids in the VWF A1 domain (K1362, R1392, R1395, R1399, and K1406). These results suggested that TAGX-0004 possessed better pharmacological properties than caplacizumab in vitro and might be similarly promising for aTTP treatment.


2002 ◽  
Vol 302 (2) ◽  
pp. 252-262 ◽  
Author(s):  
Evgueni Saenko ◽  
Christoph Kannicht ◽  
Klemens Loster ◽  
Andrey Sarafanov ◽  
Alexey Khrenov ◽  
...  

1994 ◽  
Vol 72 (02) ◽  
pp. 180-185 ◽  
Author(s):  
David J Mancuso ◽  
Elodee A Tuley ◽  
Ricardo Castillo ◽  
Norma de Bosch ◽  
Pler M Mannucci ◽  
...  

Summaryvon Willebrand factor gene deletions were characterized in four patients with severe type III von Willebrand disease and alloantibodies to von Willebrand factor. A PCR-based strategy was used to characterize the boundaries of the deletions. Identical 30 kb von Willebrand factor gene deletions which include exons 33 through 38 were identified in two siblings of one family by this method. A small 5 base pair insertion (CCTGG) was sequenced at the deletion breakpoint. PCR analysis was used to detect the deletion in three generations of the family, including two family members who are heterozygous for the deletion. In a second family, two type III vWD patients, who are distant cousins, share an -56 kb deletion of exons 22 through 43. The identification and characterization of large vWF gene deletions in these type III vWD patients provides further support for the association between large deletions in both von Willebrand factor alleles and the development of inhibitory alloantibodies.


Langmuir ◽  
2006 ◽  
Vol 22 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Taewook Kang ◽  
Surin Hong ◽  
Hyun Jin Kim ◽  
Jungwoo Moon ◽  
Seogil Oh ◽  
...  

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