Alkynyl phosphates are potent inhibitors of serine enzyme

[摘要]

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 10⁷–10⁸ M⁻¹ min⁻¹. Most proteases were inhibited with a rate constant of 10⁴–10⁵ 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.

[学科分类] 生物化学/生物物理

[关键词] Alkynyl phosphate;Covalent inhibition;Serine enzyme;AChE;acetylcholinesterase;BChE;butyrylcholinesterase;CT;chymotrypsin;t-BEDEP;1-t-butylethynyl diethyl phosphate;HDEP;1-hexynyl diethyl phosphate;PDEP;1-propynyl diethyl phosphate;DFP;diisopropyl fluoro phosphate;TCA;trichloroacetic acid;PAM;pyridine aldoxime methiodide;Z-Ala-pNP;benzyloxycarbonyl-l-alanine p-nitrophenyl ester;BAEE;benzoylarginine ethyl ester;ATEE;acetyltyrosine ethyl ester;PMSF;phenylmethanesulfonyl fluoride;cpm;counts per minute