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Article Dans Une Revue Journal of Thrombosis and Haemostasis Année : 2006

Intrinsic stability and functional properties of disulfide bond-stabilized coagulation factor VIIIa variants

Résumé

The utility of purified coagulation factor (F)VIII for treatment of hemophilia A is limited in part by its instability following activation by thrombin, which is caused by spontaneous dissociation of the A2 domain from the activated FVIII (FVIIIa) heterotrimer. To prevent this A2 domain dissociation in FVIIIa, we previously engineered a cysteine pair (C664-C1826) in recombinant FVIII that formed a disulfide bond cross-linking the A2 domain in the heavy chain to the A3 domain in the light chain. This engineered disulfide bond resulted in a more stable FVIIIa.
Here, we characterize the functional parameters of C664-C1828 FVIII and of a new disulfide bond-stabilized FVIII (C662-C1828 FVIII).

Dates et versions

hal-03242813 , version 1 (31-05-2021)

Identifiants

Citer

A. Gale, K.-P. Radtke, M. Cunningham, D. Chamberlain, Jean-Luc Pellequer, et al.. Intrinsic stability and functional properties of disulfide bond-stabilized coagulation factor VIIIa variants. Journal of Thrombosis and Haemostasis, 2006, 4 (6), pp.1315-1322. ⟨10.1111/j.1538-7836.2006.01951.x⟩. ⟨hal-03242813⟩
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