Factor VIII, a human blood plasma protein, plays an important role during the intrinsic pathway of blood coagulation cascade after its activation by thrombin. The activated form of FVIII acts as cofactor to the serine protease Factor IXa, in the conversion of the zymogen Factor X to the active enzyme Factor Xa. The Ser558–Gln565 region of the A2 subunit of Factor VIII has been shown to be crucial for FVIIIa–FIXa interaction. Based on this, a series of linear peptides, analogs of the 558–565 loop of the A2 subunit of the heavy chain of Factor VIII were synthesized using the acid labile 2-chlorotrityl chloride resin and biologically evaluated in vitro by measuring the chronic delay of activated partial thromboplastin time and the inhibition of Factor VIII activity, as potential anticoagulants.
Factor VIII Anticoagulant activity Activated partial thromboplastin time Synthetic peptides Blood coagulation cascade FVIII-FIX interaction
Reversed phase high performance liquid chromatography
Thin layer chromatography
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Anticoagulant assays were performed under the supervision of Professor of Haematology, Dr Pantelis Makris, School of Medicine, Aristotle University of Thessaloniki, Greece. This Research Project is co-financed: 80 % by European Union—European Social Fund and 20 % by General Secretary of Research & Technology (PENED 03ED569). We also thank SANOFI S.A., Athens, Greece for the financial support.
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