A leading cause of death in Western society is due to the inappropriate formation of blood clots. Clots form due to the coagulation cascade, leading to the formation by thrombin of fibrin from fibrinogen, forming an insoluble polymer. Direct inhibition of thrombin would result in a reduction of clot formation. In the work presented here, blood clots were formed in a fibrinogen and thrombin-containing clotting assay. Triplicate assays each of uninhibited, inhibited using acet-ISPR-amide and acet-LSPR-amide, and inhibited using the commercial irreversible serine protease inhibitor Pefabloc ®, were analyzed by visible spectroscopy to determine if clot inhibition occurred. Acet-ISPR-amide and acet-LSPR-amide provided slight but significant inhibition at 14 mM, compared to the uninhibited case; however the 30 μM concentration, for both the acet-ISPR-amide and acet-LSPR-amide, demonstrated more inhibition than the 14 μM and uninhibited case. The spectra were then fit to a sigmoidal curve using the three-coefficient Hill equation. Coefficient “a” provided the maximum clot density (clotmax), coefficient “b” showed the level of cooperativity in clot formation as a function of the sigmoidality of the curve, while “c” provided the time of half clot formation (time1/2clot). The clot density was similar throughout the first three cases; however Pefabloc ® was slightly smaller. The time1/2clot increased as the concentration of each peptide inhibitor increased.

Inhibition of formation of blood clots by tetrapeptide inhibitors acet-LSPR-amide and acet-ISPR-amide

249th National Meeting (2015)

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