Alkynyl phosphates are potent inhibitors of serine enzyme

Abstract

Propynyl, hexynyl and t-butylethynyl diethyl phosphates were found to be very powerful covalent inhibitors of serine enzymes. Esterases were inhibited with second-order rate constants of 10(7)-10(8) m(-1) min(-1). Most proteases were inhibited with a rate constant of 10(4)-10(5) M(-1) min(-1). By inhibiting chymotrypsin with (3-14C)-1-propynyl diethyl phosphate, it was established that inhibition was caused by binding of the phosphate group to the enzyme active site.