Peptidomimetic aminomethylene ketone inhibitors of interleukin-1β- converting enzyme (ICE)

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 8, 1998, Pages 959-964

  Semple, Graeme ^a   Ashworth, Doreen M ^b   Batt, Andrzej R ^a   Baxter, Andrew J ^a   Benzies, David W M ^a   Elliot, Lucy H ^b   Evans, D Michael ^a   Franklin, Richard J ^a   Hudson, Peter ^a   Jenkins, Paul D ^a   Pitt, Gary R ^a   Rooker, David P ^a   Yamamoto, Satoshi ^c   Isomura, Yasuo ^c  

^a Chilworth Research Centre   (United Kingdom)

^b UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^c Yamanouchi Inst Drug Discov Res   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

DIPYRONE; INTERLEUKIN 1BETA CONVERTING ENZYME INHIBITOR; KETONE;

ARTICLE; DRUG SOLUBILITY; ENZYME INHIBITION; SOLUBILITY; STRUCTURE ACTIVITY RELATION;

AMIDES; CASPASE 1; CYSTEINE PROTEINASE INHIBITORS; HUMANS; KINETICS; MOLECULAR STRUCTURE; PYRIDONES; RECOMBINANT PROTEINS; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 18844474053     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00136-X     Document Type: Article

References (12)

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10. i values were determined using standard Dixon Plots and are ± S.E.M.
11. + 1 3.68 4.26 <0.2mg/mL 2 5.53 4.73 0.46mg/mL 6n 2.30 n.d. 0.9mg/mL 6e 0.91 n.d. >1.2mg/mL † Approximate solubility in 0.1% MeCN/0.1M Tris buffer at pH 7.4
12. 11) Irreversible inhibition was characterised by the lack of substrate turnover following pre-incubation of enzyme and inhibitor for up to 20 min prior to addition of substrate. All the compounds described herein were reversible inhibitors and hence the progress curves were independent of the order of addition of enzyme or inhibitor to the substrate/buffer mixture.