- Possible involvement of radical intermediates in the inhibition of cysteine proteases by allenyl esters and amides
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In order to investigate crystallographically the mechanism of inhibition of cysteine protease by α-methyl-γ,γ-diphenylallenecarboxylic acid ethyl ester 3, a cysteine protease inhibitor having in vivo stability, we synthesized N-(α-methyl-γ,γ-diphenylallenecarbonyl)-l-phenylalanin e ethyl ester 4. Reaction of 4 with thiophenol, the SH group of which has similar pKa value to that of cysteine protease, produced oxygen-mediated radical adducts 6 and 7 in ambient air but did not proceed under oxygen-free conditions. Catalytic activities of two thiol enzymes including cathepsin B were also lowered in the absence of oxygen. These results suggest that cysteine protease can act through an oxygen-dependent radical mechanism.
- Takeuchi, Yoshio,Fujiwara, Tomoya,Shimone, Yoshihito,Miyataka, Hideki,Satoh, Toshio,Kirk, Kenneth L.,Hori, Hitoshi
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scheme or table
p. 6202 - 6205
(2009/08/07)
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