The action of thrombin on modified fibrinogen.
The modification of canine fibrinogen with citraconic anhydride modified the epsilon-amino groups of the fibrinogen and at the same time generated additional negative charges into the protein. The addition of thrombin to the modified fibrinogen did not induce polymerization; however, the fibrinopeptide was released at a faster rate than from the unmodified fibrinogen. The physical properties of the citraconylated fibrinogen were markedly altered by the modification of 50-60 lysine residues in one hour. A modified fibrinopeptide-A was released by thrombin from the modified fibrinogen and was electrophoretically more anionic than the unmodified fibrinopeptide-A. Edman analysis confirmed the modification of the lysine residue present in the peptide. The rate of removal of citraconylated fibrinopeptide-A from modified fibrinogen by thrombin was 30 to 40 percent greater than the cleavage of unmodified fibrinopeptide-A from unmodified fibrinogen. However, the modification of 60 or more lysine residues in the fibrinogen produced a decrease in the rate of cleavage of citraconylated fibrinopeptide-A. The results suggest that additional negative charge in the vicinity of the attachment of fibrinopeptide-A to canine fibrinogen aids in the removal of the peptide by thrombin.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002949:Citraconic Anhydrides / Q000494:pharmacology*; D004285:Dogs; D005340:Fibrinogen / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000032:analysis / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D007700:Kinetics; D008239:Lysine / Q000032:analysis / Q000378:metabolism; D046911:Macromolecular Substances; D013917:Thrombin / Q000494:pharmacology*
D000596:Amino Acids; D002949:Citraconic Anhydrides; D005663:Furans; D046911:Macromolecular Substances; D005344:Fibrinopeptide A; D005340:Fibrinogen; D013917:Thrombin; D008239:Lysine