Peptidyl antithrombogenic agents for extracorporeal blood circulation.
The reduction of platelet aggregation and adhesion is essential for preventing thrombus formation during extracorporeal circulation. This report addresses some performances of peptidyl antithrombogenic agents which bind to the adhesive site of fibrinogen. This was based on the recent finding that the sequence of the binding domain of the platelet membrane receptor to fibrinogen was identified as TDVNGDGRHDL (one-letter amino acid code; Thr-Asp-Val-Asn-Gly-Asp-Gly-Arg-His-Asp-Leu), entitled B12. The addition of B12 and shorter-chain analogue peptides dose-dependently suppressed platelet aggregation and adhesion onto a fibrinogen-coated surface. The shorter the amino acid sequence, the less effective was inhibition. The inhibitory effect on platelet adhesion in vivo was significant under continuous infusion of B12. These inhibitory effects were compared with those by a receptor-binding RGD (Arg-Gly-Asp) peptide, which is the common active site to adhesive proteins.
Ito
S
S
Department of Bioengineering, Osaka City University Medical College, Japan.
Matsuda
T
T
Takemoto
Y
Y
Yamamoto
K
K
Kishimoto
T
T
Maekawa
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D004285:Dogs; D005112:Extracorporeal Circulation; D005340:Fibrinogen / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D017348:Microscopy, Electron, Scanning Transmission; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen; C046617:arginyl-glycyl-aspartyl-serine