PPACK (trifluoroacetate salt) (Synonyms: Pebac, DPhenylalanylprolylarginyl Chloromethyl Ketone)

PPACK is a synthetic peptide derivative that irreversibly and specifically inhibits thrombin-mediated platelet activation by binding with high affinity to the active site of thrombin (K_i = 0.24 nM).^1,2,3 It has been used as an anticoagulant (100 μM) and to study thrombin-mediated fibrin deposition, angiogenesis, and proinflammatory processes.^4,5

1.Kovach, I.M., Kelley, P., Eddy, C., et al.Proton bridging in the interactions of thrombin with small inhibitorsBiochemistry48(30)7296-7304(2009) 2.Bode, W., Turk, D., and Karshikov, A.The refined 1.9-Å x-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human α-thrombin: Structure analysis, overall structure, electrostatic properties, detailed active-site geometry, and structure-function relationshipsProtein Science1(4)426-471(1992) 3.Hanson, S.R., and Harker, L.A.Interruption of acute platelet-dependent thrombosis by the synthetic antithrombin D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketoneProceedings of the National Academy of Sciences of the United States of America85(9)3184-3488(1988) 4.Lyon, M.E., Fine, J.S., Henderson, P.J., et al.D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK): Alternative anticoagulant to heparin salts for blood gas and electrolyte specimensClinical Chemistry41(7)1038-1041(1995) 5.Liu, J.F., Hou, S.M., Tsai, C.H., et al.Thrombin induces heme oxygenase-1 expression in human synovial fibroblasts through protease-activated receptor signaling pathwaysArthritis Research & Therapy14(2)R91(2012)