TY - JOUR
T1 - Cyclic peptide analogs of 558-565 epitope of A2 subunit of Factor VIII prolong aPTT. Toward a novel synthesis of anticoagulants
AU - Anastasopoulos, C.
AU - Sarigiannis, Y.
AU - Stavropoulos, G.
PY - 2014/4/1
Y1 - 2014/4/1
N2 - 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.
AB - 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.
KW - Activated partial thromboplastin time
KW - Anticoagulant activity
KW - Antithrombotic agents
KW - Factor VIII
KW - FVIII-FIX interaction
KW - Peptoid-peptides
KW - Synthetic cyclic peptides
UR - http://www.scopus.com/inward/record.url?scp=84898879809&partnerID=8YFLogxK
U2 - 10.1007/s00726-014-1673-7
DO - 10.1007/s00726-014-1673-7
M3 - Article
C2 - 24464027
AN - SCOPUS:84898879809
SN - 0939-4451
VL - 46
SP - 1087
EP - 1096
JO - Amino Acids
JF - Amino Acids
IS - 4
ER -