Inhibition of cancer procoagulant by peptidyl diazomethyl ketones and peptidyl sulfonium salts.
Cancer procoagulant (CP) is a cysteine proteinase from cancer cells that initiates blood coagulation. Members of two classes of unique and highly specific cysteine proteinase inhibitors, peptidyl diazomethyl ketones (PDK) and peptidyl sulfonium salts (PSS), were studied to determine whether or not they inhibited CP. The inhibitors did not impair the activity of the coagulation system. There was a differential inhibitory effect of the 6 PDK and 2 PSS inhibitors, influenced by the amino acid composition or sequence of the peptide moiety, that suggests differences in structural features of the active site of CP and papain. CP was inhibited by both classes of inhibitors.
Mario Negri Institute, Milan, Italy.
A
A
Falanga
E
E
Shaw
M B
MB
Donati
R
R
Consonni
T
T
Barbui
S
S
Gordon
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors; D003978:Diazomethane / Q000031:analogs & derivatives* / Q000494:pharmacology; D009363:Neoplasm Proteins; D009861:Onium Compounds / Q000494:pharmacology*; D010206:Papain / Q000037:antagonists & inhibitors; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D013452:Sulfonium Compounds / Q000494:pharmacology*; D013925:Thromboplastin / Q000037:antagonists & inhibitors; D014121:Toxoids; D014757:Viper Venoms / Q000037:antagonists & inhibitors
D001779:Blood Coagulation Factors; D015853:Cysteine Proteinase Inhibitors; D009363:Neoplasm Proteins; D009861:Onium Compounds; D010455:Peptides; D013452:Sulfonium Compounds; D014121:Toxoids; D014757:Viper Venoms; C050899:viper venoid; D003978:Diazomethane; D013925:Thromboplastin; D003546:Cysteine Endopeptidases; D010206:Papain; C030910:cancer procoagulant