Interleukin-1/3- converting enzyme

This ceramide-mediated apoptosis was shown to be inhibited by the simultaneous addition of PKC activators (Ni et at, 1994 Obeid et al, 1993), implying that PS may activate the ceramide-mediated apoptotic pathway. However, the inhibitors of interleukin-1 converting enzyme (ICE)-like proteases (Caspase), such as tosyl-L-lysine chloromethyl ketone (TLCK), and tosyl-L-phenylalanine chloromethyl ketone (TPCK) which inhibit ceramide-mediated apoptosis, had no effect on PS-induced apoptosis (Figure 4). Thus, PS-induced apoptotic pathway appears to be distinct from that mediated by ceramide. Further studies are required to clarify the molecular mechanisms underlying the PS-induced apoptosis. 

The application of multiple reaction parameters executed in a parallel array format has been used to expedite the identification of optimal conditions for the synthesis of a collection of almost 600 new interleukin-1/ converting enzyme inhibitors [89]. The reaction in question was the problematic conversion of a / -tert-butyl aspartic acid bromoethylketone to the corresponding acyloxyketone (Scheme 2.63). The study en-... 

Yamin TT, Ayala JM, Miller DK (1996), Activation of the native 45-kDa precursor form of interleukin-1-converting enzyme, J. Biol. Chem. 271 13273-13282. 

Peptidomimetic modifications of the tet-rapeptide sequence have led to the conforma-tionally constrained compound (69)as a selective inhibitor of caspase-1 or interleukin-1 converting enzyme (ICE) as potential anti-inflammatory compounds (131). Recently, new non-peptide peptidomimetic diphenyl ether sulfonamides have been described as novel lead structures (70) (Fig. 15.32) (132). 

Fulda S, Meyer E, Debatin KM. Metabolic inhibitors sensitize for CD95 (APO-1/ Fas)-induced apoptosis by down-regulating Fas-associated death domain-like interleukin 1-converting enzyme inhibitory protein expression. Cancer Res 2000 60 3947-3956. 

NEMO kinase (regulatory subunit IKKy), NFkB (nuclear factor kappa B lymphoma) essential modulator, inhibitor of kappa kinase gamma (IKKy). Protein kinase C-interacting protein p62/sequestosome-l, is activated by interleukin IL-IP in sequence, it activates of nuclear factor NFkB in TNFa-stimulated cells (Zotti T et al Mol Immunol 2014 58 27-31). NEMO promotes vFFlP (Fas-associated death domain-like interleukin-1-converting enzyme inhibitory protein) expression by Kaposi sarcoma associated herpesvirus (KSHV) (Tolani B et al J Virol 2014 March 26 PMID 24672029). 

N. A., A combinatorial approach for determining protease specificities Application to interleukin-1 converting enzyme (ICE), Chem. Biol., 4 (1997) 149-155. 

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