Synthesis of taurine- and/or acetyl group-conjugated poly(D-Glu, D-Lys) derivatives and their effects on fibrinolysis.
A series of C-sulfoethylated and/or N-acetylated poly(D-Glu, D-Lys) (polyGL) derivatives was synthesized and their effects on tissue-type plasminogen activator (t-PA)-induced fibrinolysis were investigated. These derivatives accelerated t-PA-induced plasma (fibrin) clot lysis and t-PA-catalyzed plasminogen activation with the following order of potency: C-sulfoethylated and N-acetylated polyGL greater than N-acetylated polyGL greater than C-sulfoethylated polyGL greater than polyGL. The most potent stimulator C-sulfoethylated and N-acetylated polyGL associated with both t-PA and plasminogen under low ionic conditions, whereas it did not prevent the bindings of t-PA and plasminogen to fibrin. These results suggest that t-PA and plasminogen preferentially bind to sulfated or carboxylated polyanions, which may be required to possess certain neutral groups, and such complex formation may improve the plasminogen activation kinetics in a different manner from that of fibrin.
Soeda
S
S
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Ohki
H
H
Shimeno
H
H
Nagamatsu
A
A
D000107:Acetylation; D001665:Binding Sites / Q000187:drug effects; D002384:Catalysis; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis*; D010958:Plasminogen / Q000378:metabolism; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011107:Polylysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D013654:Taurine / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D010455:Peptides; D013654:Taurine; D011107:Polylysine; D011099:Polyglutamic Acid; C030391:poly(glutamic acid-lysine); D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator