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Turoctocog alfa (NovoEight®)--from design to clinical proof of concept.

Ezban M, Vad K, Kjalke M - Eur. J. Haematol. (2014)

Bottom Line: Viral inactivation is ensured by a detergent inactivation step as well as a 20-nm nano-filtration step.Tyr1680 was also fully sulphated in turoctocog alfa resulting in strong affinity (low nm Kd ) for binding to von Willebrand factor (VWF).The non-clinical data thus confirm the haemostatic effect of turoctocog alfa and, together with the comprehensive clinical evaluation, support the use as FVIII replacement therapy in patients with haemophilia A.

View Article: PubMed Central - PubMed

Affiliation: Novo Nordisk A/S, Maaloev, Denmark.

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Crystallographic structure of turoctocog alfa. The heavy chain consists of the A1 (blue) and A2 (red) domain while the light chain consists of the A3 (yellow), C1 (grey) and C1 (black) domains. The three ions, calcium (green), copper (blue) and zink (red), observed in the structure are shown as spheres. The structure is available at protein database with the entry code 4bdv (http://www.rcsb.org/pdb/explore/explore.do?structureId=4BDV) 29.
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fig04: Crystallographic structure of turoctocog alfa. The heavy chain consists of the A1 (blue) and A2 (red) domain while the light chain consists of the A3 (yellow), C1 (grey) and C1 (black) domains. The three ions, calcium (green), copper (blue) and zink (red), observed in the structure are shown as spheres. The structure is available at protein database with the entry code 4bdv (http://www.rcsb.org/pdb/explore/explore.do?structureId=4BDV) 29.

Mentions: The purity and homogeneity of turoctocog alfa allowed crystallisation of the protein. The resulting X-ray crystallographic structure of turoctocog alfa (Fig.4) confirms that the protein has a structure similar to those previously reported for other rFVIII molecules 27,28. The X-ray fluorescence wavelength scan of the turoctocog alfa crystals identified two significant peaks, indicating copper (Cu+) and zinc (Zn2+), respectively 29. The presence of both copper and zinc was supported by colorimetric data, indicating that the ion-binding site in the A1 domain is predominantly populated by zinc, while that in the A3 domain is predominantly populated by copper 29.


Turoctocog alfa (NovoEight®)--from design to clinical proof of concept.

Ezban M, Vad K, Kjalke M - Eur. J. Haematol. (2014)

Crystallographic structure of turoctocog alfa. The heavy chain consists of the A1 (blue) and A2 (red) domain while the light chain consists of the A3 (yellow), C1 (grey) and C1 (black) domains. The three ions, calcium (green), copper (blue) and zink (red), observed in the structure are shown as spheres. The structure is available at protein database with the entry code 4bdv (http://www.rcsb.org/pdb/explore/explore.do?structureId=4BDV) 29.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232928&req=5

fig04: Crystallographic structure of turoctocog alfa. The heavy chain consists of the A1 (blue) and A2 (red) domain while the light chain consists of the A3 (yellow), C1 (grey) and C1 (black) domains. The three ions, calcium (green), copper (blue) and zink (red), observed in the structure are shown as spheres. The structure is available at protein database with the entry code 4bdv (http://www.rcsb.org/pdb/explore/explore.do?structureId=4BDV) 29.
Mentions: The purity and homogeneity of turoctocog alfa allowed crystallisation of the protein. The resulting X-ray crystallographic structure of turoctocog alfa (Fig.4) confirms that the protein has a structure similar to those previously reported for other rFVIII molecules 27,28. The X-ray fluorescence wavelength scan of the turoctocog alfa crystals identified two significant peaks, indicating copper (Cu+) and zinc (Zn2+), respectively 29. The presence of both copper and zinc was supported by colorimetric data, indicating that the ion-binding site in the A1 domain is predominantly populated by zinc, while that in the A3 domain is predominantly populated by copper 29.

Bottom Line: Viral inactivation is ensured by a detergent inactivation step as well as a 20-nm nano-filtration step.Tyr1680 was also fully sulphated in turoctocog alfa resulting in strong affinity (low nm Kd ) for binding to von Willebrand factor (VWF).The non-clinical data thus confirm the haemostatic effect of turoctocog alfa and, together with the comprehensive clinical evaluation, support the use as FVIII replacement therapy in patients with haemophilia A.

View Article: PubMed Central - PubMed

Affiliation: Novo Nordisk A/S, Maaloev, Denmark.

Show MeSH
Related in: MedlinePlus