A novel approach in potential anticoagulants from peptides epitope 558–565 of A2 subunit of factor VIII

• Published in: Amino acids Vol. 44; no. 4; pp. 1159 - 1165
• Main Authors: Anastasopoulos, C., Sarigiannis, Y., Stavropoulos, G.
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.04.2013
• Subjects: Activated; Activation; Amino Acid Motifs; Amino Acid Sequence; Analytical Chemistry; Anticoagulants; Anticoagulants - chemical synthesis; Anticoagulants - chemistry; Anticoagulants - metabolism; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Cascades; Chlorides; Drug Design; Enzymes; Factor IXa - metabolism; Factor VIII - chemical synthesis; Factor VIII - chemistry; Factor VIII - genetics; Factor VIII - metabolism; Factor X - metabolism; Humans; Life Sciences; Molecular Sequence Data; Neurobiology; Original Article; Peptides; Peptides - chemical synthesis; Peptides - chemistry; Peptides - genetics; Peptides - metabolism; Protein Binding; Proteomics; Solid-Phase Synthesis Techniques - methods; Thrombin; Blood coagulation cascade; Synthetic peptides; Activated partial thromboplastin time; Anticoagulant activity; Factor VIII; FVIII-FIX interaction
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-012-1448-y

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 Ser 558 –Gln 565 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.