Cyclic peptide analogs of 558–565 epitope of A2 subunit of Factor VIII prolong aPTT. Toward a novel synthesis of anticoagulants

• Published in: Amino acids Vol. 46; no. 4; pp. 1087 - 1096
• Main Authors: Anastasopoulos, C, Sarigiannis, Y, Stavropoulos, G
• Format: Journal Article
• Language: English
• Published: Vienna Springer-Verlag 01.04.2014; Springer Vienna; Springer Nature B.V
• Subjects: Amino Acid Sequence; Analogs; Analytical Chemistry; anticoagulant activity; Anticoagulants; Anticoagulants - chemical synthesis; Anticoagulants - chemistry; Anticoagulants - pharmacology; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Blood coagulation; Blood Coagulation - drug effects; Chlorides; disease prevention; epitopes; Epitopes - chemistry; Epitopes - pharmacology; factor VIII; Factor VIIIa - chemical synthesis; Factor VIIIa - chemistry; Factor VIIIa - pharmacology; factors; Humans; Inhibition; Life Sciences; Medical services; Molecular Structure; monitoring; Neurobiology; Original Article; Partial Thromboplastin Time; Peptides; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - chemistry; Peptides, Cyclic - pharmacology; Protein Subunits - chemical synthesis; Protein Subunits - chemistry; Protein Subunits - metabolism; Proteomics; Synthesis; thromboplastin; thrombosis; Activated partial thromboplastin time; Synthetic cyclic peptides; Factor VIII; Antithrombotic agents; Peptoid-peptides; FVIII–FIX interaction; Anticoagulant activity
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-014-1673-7

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.