The synthesis and properties of peptidylmethylsulphonium salts with two cationic residues as potential inhibitors of prohormone processing.
Peptidylmethylsulphonium salts incorporating consecutive basic residues at the C-terminus of the peptidyl portion such as -Arg-Arg-, -Arg-Lys-, -Lys-Lys- and -Lys-Arg- were synthesized and examined as proteinase inhibitors. Serine proteinases with a specificity directed towards hydrolysis at cationic residues were found to be unaffected by these derivatives. On the other hand, cysteine proteinases, cathepsin B and, in particular, clostripain were readily inactivated by affinity labelling. The reagents thus are of promise for the study of prohormone processing promoted by cysteine proteinases.
Zumbrunn
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A
Friedrich Miescher-Institut, Basel, Switzerland.
Stone
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S
Shaw
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E
D002401:Cathepsin B / Q000037:antagonists & inhibitors; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides / Q000138:chemical synthesis*; D009861:Onium Compounds / Q000138:chemical synthesis*; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D013452:Sulfonium Compounds / Q000138:chemical synthesis*
D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D009861:Onium Compounds; D011480:Protease Inhibitors; D013452:Sulfonium Compounds; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C019913:clostripain