Peptidic p-nitroanilide substrates of interleukin-1 beta-converting enzyme.
Peptidic p-nitroanilides are useful colorimetric substrates for enzymes. With the aim of developing a convenient, quantitative assay for inhibitors of interleukin-1 beta-converting enzyme (ICE), we have explored three approaches to the synthesis of peptidic p-nitroanilides relevant to this enzyme. The first approach involved a late stage oxidation of a p-aminoanilide such as CbzValAlaAsp(beta- tert-butyl)-p-(t-Boc-amino)anilide. The second and third approaches used the preformed amino acid p-nitroanilides HAsp-p-nitroanilide hydrochloride and HAsp(beta-tert-butyl)-p-nitroanilide which were coupled iteratively with preactivated amino acid derivatives or with an appropriate peptide, respectively. While each approach had it merits and limitations, all three produced p-nitroanilides that were substrates for ICE.
Reiter
L A
LA
Department of Medicinal Chemistry, Pfizer Inc, Groton, Connecticut.
D000595:Amino Acid Sequence; D000596:Amino Acids; D000813:Anilides / Q000138:chemical synthesis* / Q000378:metabolism; D000814:Aniline Compounds / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D020170:Caspase 1; D003124:Colorimetry; D005449:Fluorenes; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism; D013379:Substrate Specificity
D000596:Amino Acids; D000813:Anilides; D000814:Aniline Compounds; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009842:Oligopeptides; C019498:4-nitroaniline; D001224:Aspartic Acid; D020170:Caspase 1; D008666:Metalloendopeptidases