64356-74-7Relevant articles and documents
β-Lactones as a new class of cysteine proteinase inhibitors: inhibition of hepatitis A virus 3C proteinase by N-Cbz-serine β-Lactone
Lall, Manjinder S.,Karvellas, Constantine,Vederas, John C.
, p. 803 - 806 (2008/02/12)
Formula presented N-Benzyloxycarbonyl-L-serine β-lactone (1) is shown to irreversibly inactivate the 3C cysteine proteinase of hepatitis A virus (HAV) with kinact = 0.70 min-1, KI = 1.84 x 10-4 M and kinact/KI = 3800 M-1 min-1 at an enzyme concentration of 0.1 μM. Mass spectrometric and HMQC NMR studies using 13C-labeled 1 show that the active site cysteine (Cys-172) thiol of the HAV 3C proteinase attacks the β-position (i.e. C-4) of the oxetanone ring, thereby leading to ring opening and alkylation of the sulfur. In contrast, the enantiomer of this β-lactone, 2, is a reversible competitive inhibitor (Ki = 1.50 x 10-6 M) at similar enzyme concentrations. The β-lactone motif represents a new class of inhibitors of cysteine proteinases.
