Pumpkin seed inhibitor of human factor XIIa (activated Hageman factor) and bovine trypsin

Biochemistry ◽  
1982 ◽  
Vol 21 (16) ◽  
pp. 3741-3746 ◽  
Author(s):  
Yoshio Hojima ◽  
Jack V. Pierce ◽  
John J. Pisano
Keyword(s):  
Human Factor ◽  
Pumpkin Seed ◽  
Hageman Factor ◽  
Bovine Trypsin ◽  
Factor Xiia

scholarly journals The synthesis of arginylfluoroalkanes, their inhibition of trypsin and blood-coagulation serine proteinases and their anticoagulant activity

1990 ◽  
Vol 265 (2) ◽  
pp. 539-545 ◽  
Author(s):  
T Ueda ◽  
C M Kam ◽  
J C Powers
Keyword(s):  
Blood Coagulation ◽  
Human Factor ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Activated Partial Thromboplastin Time ◽  
Serine Proteinases ◽  
Bovine Thrombin ◽  
Bovine Trypsin ◽  
Factor Xiia ◽  
Factor Xia

Seven arginylfluoroalkanes (‘arginine fluoroalkyl ketones’) were synthesized by using a modified Dakin-West procedure. The structure of benzoyl-Arg-CF2CF3 was analysed by 19F-n.m.r. spectroscopy and m.s. and the compound was shown to exist primarily as a hydrate or cyclic carbinolamine. Arginylfluoroalkanes are good inhibitors of blood-coagulation serine proteinases and were found to be slow-binding inhibitors for bovine trypsin with Ki values of 0.2-56 microM. Benzoyl-Arg-CF2CF3 was the best inhibitor for bovine thrombin and human Factor XIa, and inhibited thrombin and Factor XIa competitively with Ki values of 13 microM and 62 microM respectively. The best inhibitor for pig pancreatic kallikrein was p-toluoyl-Arg-CF3, with a Ki value of 35 microM. Benzoyl-Arg-CF3 and benzoyl-Arg-CF2CF3 inhibited human plasma kallikrein competitively, with Ki values of 50 microM. None of the seven arginylfluoroalkanes was a good inhibitor of human factor Xa or of Factor XIIa. The arginylfluoroalkanes were tested in the prothrombin time (PT) and activated partial thromboplastin time (APTT) coagulant assays. Two fluoroketones, benzoyl-Arg-CF2CF3 and 1-naphthoyl-Arg-CF3, had significant anticoagulant activity. Benzoyl-Arg-CF2CF3 was found to prolong the PT 1.8-fold at 120 microM and to prolong the APTT 2.4-fold at 90 microM, whereas 1-naphthoyl-Arg-CF3 only prolonged the APTT 1.7-fold at 100 microM.

INTERACTIONS OF DYSFUNCTIONAL Cl-INHIBITORS FROM PATIENTS WITH TYPE II HEREDITARY ANGIONEUROTIC EDEMA (HANE) WITH ACTIVATED HAGEMAN FACTOR (FACTOR XIIa).

1987 ◽  
Author(s):  
V H Donaldson ◽  
M D B H Mitchell
Keyword(s):  
Normal Serum ◽  
Type Ii ◽  
Inhibitor Protein ◽  
Amidolytic Activity ◽  
Hageman Factor ◽  
Hereditary Angioneurotic Edema ◽  
Coagulant Activity ◽  
Antigenic Properties ◽  
Factor Xiia

Type II HANE is characterized by a deficiency of Cl-inhibitor (Cl-INH) activity in serum which is associated with a dysfunctional inhibitor protein having a normal or increased quantity o|_the antigenic properties of normal serum Cl-inhibitor. Dysfunctional Cl-INH proteins were purified from members_of eight different kindred with Type II HANE and compared to normal Cl-inhibitor with respect to their inhibitory activity directed against the amidolytic and clot-promoting properties of purified activated Hageman factor. All but one dysfunctional Cl-inhibitor blocked the amidolytic activity of ellagic acid-activated Hageman factor; all eight blocked the clot-promoting activity of Hageman factor activated in solutions of sulfatides and BSA. The inhibition _of amidolytic activity was equal to or greater than that of normal Cl-INH (Donaldson, et al., 3. Clin. Invest. 75:124,1985). The impairment of the specific Hageman factor coagulant activity of activated Hageman factor by six^f the eight dysfunctional inhibitors was less than that of the normal Cl-inhibitor, although readily measured. Dysfunctional Cl-inhibitor proteins were also heterogeneous with respect to their formation of stable complexes and their susceptibility to cleavage by Hageman factor activated with BSA-sulfatides when analyzed in SDS-gel electrophoresis. Although these observatons cannot be directly applied to in vivo pathophysiologic changes in plasma, dysfunctional Cl-inhibitors do have the potential of regulating activated Hageman factor.

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