ADAMTS13 content and VWF multimer and triplet structure in commercially available VWF/FVIII concentrates

Biologicals ◽  
2015 ◽  
Vol 43 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Christoph Kannicht ◽  
Claudine Fisseau ◽  
Werner Hofmann ◽  
Mario Kröning ◽  
Birte Fuchs
Keyword(s):  
Triplet Structure

scholarly journals Synthesis and Photobehavior of a NewDehydrobenzoannulene-Based HOF with Fluorine Atoms: From Solution to Single Crystals Observation

2021 ◽  
Vol 22 (9) ◽  
pp. 4803
Author(s):  
Eduardo Gomez ◽  
Ichiro Hisaki ◽  
Abderrazzak Douhal
Keyword(s):  
Charge Transfer ◽  
Single Crystals ◽  
Parent Compound ◽  
Time Resolved ◽  
Strong Basis ◽  
Triplet Structure ◽  
Carboxylic Groups ◽  
Potential Applications ◽  
A Charge ◽  
Further Development

Hydrogen-bonded organic frameworks (HOFs) are the focus of intense scientific research due their potential applications in science and technology. Here, we report on the synthesis, characterization, and photobehavior of a new HOF (T12F-1(124TCB)) based on a dehydrobenzoannulene derivative containing fluorine atoms (T12F-COOH). This HOF exhibits a 2D porous sheet, which is hexagonally networked via H-bonds between the carboxylic groups, and has an interlayers distance (4.3 Å) that is longer than that of a typical π–π interaction. The presence of the fluorine atoms in the DBA molecular units largely increases the emission quantum yield in DMF (0.33, T12F-COOH) when compared to the parent compound (0.02, T12-COOH). The time-resolved dynamics of T12F-COOH in DMF is governed by the emission from a locally excited state (S1, ~ 0.4 ns), a charge-transfer state (S1(CT), ~ 2 ns), and a room temperature emissive triplet state (T1, ~ 20 ns), in addition to a non-emissive triplet structure with a charge-transfer character (T1(CT), τ = 0.75 µs). We also report on the results using T12F-ester. Interestingly, FLIM experiments on single crystals unravel that the emission lifetimes of the crystalline HOF are almost twice those of the amorphous ones or the solid T12F-ester sample. This shows the relevance of the H-bonds in the photodynamics of the HOF and provides a strong basis for further development and study of HOFs based on DBAs for potential applications in photonics.

Relevance of Intact Von Willebrand Factor (VWF) Triplet Structure for VWF Function.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1425-1425
Author(s):  
Bruce A. Schwartz ◽  
Birte Fuchs ◽  
Christoph Kannicht ◽  
Barbera Solecka ◽  
Mario Kröning
Keyword(s):  
Von Willebrand Factor ◽  
Adamts13 Activity ◽  
Collagen Binding ◽  
Major Band ◽  
Terminal Fragment ◽  
Triplet Structure ◽  
Von Willebrand ◽  
The Impact ◽  
Willebrand Factor ◽  
Terminal Domains

Abstract Abstract 1425 Introduction: The characteristic multimer pattern of plasmatic von Willebrand factor (VWF) results from asymmetric cleavage by the processing metalloprotease ADAMTS13 between Y1605/M1606 within the VWF A2 domain. In normal plasma, characteristic species of various multimeric sizes with flanking satellite bands (triplets) encircling the major band on VWF multimer gels are present. The faster and slower migrating bands encompassing a VWF multimer lack one N-terminal fragment or possess an additional N-terminal fragment, respectively. Even though the distribution of VWF satellite bands is significantly altered in some types of von Willebrand disease (VWD) and several commercial VWF concentrates, the impact of triplet structure on VWF function has not been investigated so far. Methods: Four commercially available VWF concentrates were analyzed with respect to ADAMTS13 content as well as VWF multimer- and triplet structure using agarose gel electrophoresis. ADAMTS13 activity was quantified by the fluorescence resonance energy transfer (FRET) assay. VWF zymogram gels were used to test for ADAMTS13 activity. Samples composed of different VWF triplet distribution but comparable VWF multimers were obtained by fractionation of plasmatic VWF using heparin affinity chromatography. VWF affinity to collagen was measured by surface plasmon resonance (SPR). Results: VWF concentrates markedly differed in their content of ADAMTS13 antigen and activity. A higher ADAMTS13 content correlated with an increased portion of the proteolyzed faster migrating VWF triplet band. The degree of VWF proteolysis, i.e. lack of an additional N-terminal fragment, correlated with a decreased collagen binding level measured by SPR. Conclusion: Proteolytic cleavage of N-terminal domains of VWF resulting in a higher content of faster migrating satellite bands affects the function of VWF. The impact of VWF N-terminal domains on collagen binding and potential clinical consequences of enhanced proteolysis in commercial concentrates has to be further evaluated. Disclosures: Schwartz: Octapharma: Employment. Fuchs:Octapharma: Employment. Kannicht:Octapharma: Employment. Solecka:Octapharma: Employment. Kröning:Octapharma: Employment.

ADAMTS13 Cleavage of Von Willebrand Factor (VWF) in Commercial Concentrates and Effect on VWF Function

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4354-4354
Author(s):  
Birte Fuchs ◽  
Barbera Solecka ◽  
Mario Kröning ◽  
Christoph Kannicht ◽  
Bruce A. Schwartz
Keyword(s):  
Platelet Adhesion ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Flow Chamber ◽  
Von Willebrand Disease ◽  
Terminal Fragment ◽  
Triplet Structure ◽  
Clinical Consequences ◽  
Von Willebrand ◽  
The Impact

Abstract Abstract 4354 Objective: The characteristic multimeric pattern of plasmatic VWF results from asymmetric cleavage by ADAMTS13. Regulation of VWF multimer distribution is critical for its physiological function. In human plasma, VWF multimer gels reveal species of various multimeric sizes with flanking satellite bands (triplets). The faster and slower migrating bands encompassing a VWF multimer lack one N-terminal fragment or possess an additional N-terminal fragment, respectively. Defects in VWF secretion, impaired assembly of multimers, or increased proteolysis can cause von Willebrand Disease (VWD). Distribution of VWF triplet bands is significantly altered in some plasma-derived VWF concentrates. The impact of triplet structure on VWF function has not been investigated so far. Methods: Four commercially available VWF concentrates were analyzed for ADAMTS13 content as well as VWF multimer- and triplet structure using agarose gel electrophoresis. ADAMTS13 activity was quantified by fluorescence resonance energy transfer (FRET) assay. Samples composed of different VWF triplet distribution but comparable multimers were obtained by heparin affinity chromatography. Platelet adhesion under flow was determined using a flow-chamber model. Results: VWF concentrates markedly differed with respect to their content of ADAMTS13 antigen and activity. A higher content of ADAMTS13 correlated with an altered triplet structure reflected by an increased presence of the faster migrating triplet band, indicating VWF proteolysis. VWF-mediated platelet adhesion under flow over time was increased using a VWF fraction predominantly containing the slower migrating triplet band. Conclusion: These findings suggest that an intact triplet structure has an impact on platelet adhesion at physiological high arterial shear rate conditions. The relevance of VWF N-terminal domains for platelet binding and potential clinical consequences of enhanced proteolysis in commercial concentrates has to be further evaluated. Disclosures: Fuchs: octapharma: Employment. Solecka:Octapharma: Employment. Kröning:Octapharma: Employment. Kannicht:Octapharma: Employment. Schwartz:Octapharma: Employment.

Role of Von Willebrand Factor Triplet Bands in Glycoprotein Ib-Dependent Platelet Adhesion Under Flow Conditions

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3356-3356
Author(s):  
Bruce A. Schwartz ◽  
Christoph Kannicht ◽  
Birte Fuchs ◽  
Mario Kröning ◽  
Barbera Solecka
Keyword(s):  
Shear Flow ◽  
Platelet Adhesion ◽  
Collagen Type ◽  
Peptide Sequence ◽  
High Shear ◽  
Collagen Type Iii ◽  
Flow Conditions ◽  
Triplet Structure ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Abstract 3356 Objective: Multimeric glycoprotein von Willebrand factor (VWF) exhibits a unique triplet structure of individual oligomers, resulting from ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs 13) cleavage. The faster and slower migrating triplet bands of a given VWF multimer respectively have one shorter or longer N-terminal peptide sequence. Within this peptide sequence, the A1 domain regulates interaction of VWF with platelet glycoprotein (GP)Ib. Distribution of VWF triplet bands is significantly altered in some types of VWD, however, the impact of triplet structure on VWF function has not been investigated so far. Methods: Platelet-adhesive properties of two VWF preparations with similar multimeric distribution but different triplet composition obtained by size exclusion in addition to heparin affinity chromatography were investigated for differential functional activities. Preparation A was enriched in intermediate triplet bands, while preparation B predominantly contained larger triplet bands. Collagen- and GPIb-binding was determined by surface plasmon resonance (SPR). Platelet adhesion under flow was determined using flow-chamber models. Results: Binding studies revealed that preparation A displayed a reduced affinity for recombinant GPIb, but an unchanged affinity for collagen type III, when compared to preparation B. Under high-shear flow conditions, preparation A was less active in recruiting platelets to collagen type III. Furthermore, when added to blood from patients with von Willebrand disease (VWD), defective thrombus formation was less restored. Conclusion: Thus, VWF forms lacking larger size triplet bands appear to have a decreased potential to recruit platelets to collagen-bound VWF under arterial flow conditions. By implication, changes in triplet band distribution observed in patients with VWD may result in altered platelet adhesion at high-shear flow. Disclosures: Schwartz: Octapharma: Employment. Kannicht:Octapharma: Employment. Fuchs:octapharma: Employment. Kröning:octapharma: Employment. Solecka:Octapharma: Employment.

On the triplet structure of binary liquids

2000 ◽  
Vol 113 (8) ◽  
pp. 3302-3309 ◽  
Author(s):  
S. Jorge ◽  
G. Kahl ◽  
E. Lomba ◽  
J. L. F. Abascal
Keyword(s):  
Binary Liquids ◽  
Triplet Structure

Altered von Willebrand factor subunit proteolysis and multimer processing associated with the Cys2362Phe mutation in the B2 domain

2007 ◽  
Vol 97 (04) ◽  
pp. 527-533 ◽  
Author(s):  
Luigi Marco ◽  
Lisa Gallinaro ◽  
Maryta Sztukowska ◽  
Mario Mazzuccato ◽  
Monica Battiston ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Proteolytic Processing ◽  
Triplet Structure ◽  
Von Willebrand ◽  
A2 Domain ◽  
Willebrand Factor ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity ◽  
Marked Drop

SummaryThe normal von Willebrand factor (vWF) multimer pattern results from the ADAMTS-13 cleavage of the Tyr1605-Met1606 bond in the A2 domain of vWF. We identified a patient with severe von Willebrand disease (vWD) homozygously carrying a Cys to Phe mutation in position 2362 of vWF with markedly altered vWF multimers and an abnormal proteolytic pattern. The proband’s phenotype was characterized by a marked drop in plasma vWF antigen and ristocetin cofactor activity, and a less pronounced decrease in FVIII. The vWF multimers lacked any triplet structure, replaced by single bands with an atypical mobility, surrounded by a smear, and abnormally large vWF multimers. Analysis of the plasma vWF subunit's composition revealed the 225 kDa mature form and a single 205 kDa fragment, but not the 176 kDa and 140 kDa fragments resulting from cleavage by ADAMTS-13.The 205 kDa fragment was distinctly visible, along with the normal vWF cleavage products, in the patient's parents who were heterozygous for the Cys2362Phe mutation. Their vWF levels were mildly decreased and vWF multimers were organized in triplets, but also demonstrated abnormally large forms and smearing. Our findings indicate that a proper conformation of the B2 domain, which depends on critical Cys residues, may be required for the normal proteolytic processing of vWF multimers.

Optical Characterization of Bulk GaN Grown from a Na/Ga Flux

2002 ◽  
Vol 743 ◽  
Author(s):  
K. Palle ◽  
L. Chen ◽  
H. X. Liu ◽  
B. J. Skromme ◽  
H. Yamane ◽  
...  
Keyword(s):  
Large Scale ◽  
Deep Level ◽  
Optical Characterization ◽  
Flux Method ◽  
Triplet Structure ◽  
Bulk Gan ◽  
Scale Reactor ◽  
Low Temperature Photoluminescence ◽  
Residual Zn

ABSTRACTBulk GaN crystals up to several mm in size, grown by a Na/Ga flux method, have been characterized using room and low temperature photoluminescence (PL) and panchromatic cathodoluminescence (CL) imaging. Highly resolved excitonic PL spectra are obtained for material grown in a new, large-scale reactor. The crystal polarity affects the incorporation of residual Zn and Mg or Si acceptors and the deep level luminescence bands in c-oriented platelets. A Zn (A°,X) triplet structure with unusual thermalization properties and a highly resolved structural defect related PL peak are observed. Striations are found in some of the smaller platelets by CL imaging, but are absent in the prismatic crystals.

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