A recombinant protein and a chemically synthesized peptide containing the active peptides of the platelet collagen receptors inhibit ferric chloride-induced thrombosis in a rat model.
We have previously reported that a recombinant protein (M(r) 47 kDa), which contains both active peptide of platelet receptors for types I and III collagen inhibits both types I and III collagen-induced platelet aggregation. In order to eliminate non-reactive portion of the protein, we have constructed a recombinant of rHyB (M r 6 kDa). In addition, we chemically synthesized a hybrid peptide with 30 amino acid residues (cHyB, M r 3 kDa) that contains each of the active peptide derived from platelet receptors for types I and III collagen and a linker of 12 amino acid residues. In the present investigation, we report that both rHyB and cHyB inhibit type I and type III collagen-induced platelet aggregation, and the adhesion of radiolabeled platelets onto rabbit aortic segments in a dose-dependent manner. We have used an animal model, which employs FeCl3 to induce thrombi formation to study the effectiveness of both rHyb and cHyB on preventing thrombi formation. We obtained results that show that both rHyB and cHyB can inhibit thrombi formation in a dose-dependent manner. These results suggest that either rHyB or cHyB may be a possible therapeutic agent in preventing thrombi formation.
Du
Haiming
H
Department of Medicine, University of Tennessee-Health Science Center, Memphis, TN 38104, United States.
Zawaski
Janice A
JA
Gaber
M Waleed
MW
Chiang
Thomas M
TM
D000818:Animals; D001483:Base Sequence; D002712:Chlorides; D024042:Collagen Type I / Q000494:pharmacology; D024061:Collagen Type III / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D005290:Ferric Compounds / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D038981:Receptors, Collagen / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*
D002712:Chlorides; D024042:Collagen Type I; D024061:Collagen Type III; D017931:DNA Primers; D005290:Ferric Compounds; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D038981:Receptors, Collagen; D011994:Recombinant Proteins; C024555:ferric chloride