GTC Biotherapeutics (fka GTCB)

[DewDiligence]

Cofactor-Induced and Mutational Activity Enhancement of FVIIa

[This paper may be of interest to hard-core chemists, but the rest of us probably wouldn’t understand very much of it. The author works for Novo Nordisk, the maker of NovoSeven.]

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=HistorySearch&query_key=2&WebEnv=0O9oJQ0C5wZku5JVJaV-sXLUxLOLuI8Y-OuzwBQZRCr-qsKyNjC1eAG4YY6Bl_kAVVQTRI3qvAU8N%401FBF01FC6FC15320_0040SID&WebEnvRq=1&db=pubmed

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Cell Mol Life Sci. 2007 Dec 8.

Olsen OH, Persson E.

Haemostasis Biochemistry, Novo Nordisk A/S, Novo Nordisk Park, DK-2760, Måløv, Denmark.

Coagulation factor VIIa (FVIIa) is an atypical member of the trypsin family of serine proteases. It fails to attain spontaneously its catalytically competent conformation and requires its protein cofactor tissue factor (TF) to accomplish this. Over a number of years, this unique behaviour of FVIIa has prompted investigations of the TF-induced activation mechanism and the zymogenicity determinants in factor VIIa. Factor VIIa has gained additional interest in the past decade because of its development into a clinically useful haemostatic agent. Here, we present an overview of the current knowledge about the TF-induced allosteric activation of FVIIa and the various molecular approaches to enhance the intrinsic activity and efficacy of FVIIa.
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