(S)-Thiirancarboxylic acid as a reactive building block for a new class of cysteine protease inhibitors.
For (S)-thiirancarboxylic acid a second-order rate constant of k2nd = 222 M(-1) min(-1) for the irreversible inhibition of papain was determined. The ethyl and methyl ester do not inhibit the enzyme time-dependently. An improved synthesis of enantiomerically pure thiirancarboxylic acid is described. It is shown that thiirancarboxylates can be substrates for serine proteases (alpha-chymotrypsin) and esterases (pig liver esterase) and even for metallo proteases (thermolysin).
Schirmeister
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Institute for Pharmacy and Food Chemistry, University of Würzburg, Germany. schirmei@pharmazie.uni-wuerzburg.de
D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry* / Q000378:metabolism; D002918:Chymotrypsin / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004950:Esterases / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D013379:Substrate Specificity; D013552:Swine; D013820:Thermolysin / Q000378:metabolism
D002264:Carboxylic Acids; D015853:Cysteine Proteinase Inhibitors; D006571:Heterocyclic Compounds; C419887:thiirancarboxylic acid; D004950:Esterases; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D013820:Thermolysin