Cyclic peptide analogs of 558-565 epitope of A2 subunit of Factor VIII prolong aPTT. Toward a novel synthesis of anticoagulants.
Novel anticoagulant therapies target specific clotting factors in blood coagulation cascade. Inhibition of the blood coagulation through Factor VIII-Factor IX interaction represents an attractive approach for the treatment and prevention of diseases caused by thrombosis. Our research efforts are continued by the synthesis and biological evaluation of cyclic, head to tail peptides, analogs of the 558-565 sequence of the A2 subunit of FVIII, aiming at the efficient inhibition of Factor VIIIa-Factor IXa interaction. The analogs were synthesized on solid phase using the acid labile 2-chlorotrityl chloride resin, while their anticoagulant activities were examined in vitro by monitoring activated partial thromboplastin time and the inhibition of Factor VIII activity. The results reveal that these peptides provide bases for the development of new anticoagulant agents.
Department of Chemistry, University of Patras, Patras, Greece.
C
C
Anastasopoulos
Y
Y
Sarigiannis
G
G
Stavropoulos
D000595:Amino Acid Sequence; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D000939:Epitopes / Q000737:chemistry / Q000494:pharmacology; D015944:Factor VIIIa / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010314:Partial Thromboplastin Time; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021122:Protein Subunits / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D000925:Anticoagulants; D000939:Epitopes; D010456:Peptides, Cyclic; D021122:Protein Subunits; D015944:Factor VIIIa