Aza-Peptide Epoxides: Potent and Selective Inhibitors of Schistosoma mansoni and Pig Kidney Legumains (Asparaginyl Endopeptidases)
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K. E. James
Abstract
Aza-peptide epoxides are a new class of irreversible cysteine protease inhibitors. Derivatives containing a P1 aza-asparagine residue are specific for Schistosoma mansoni and pig kidney legumains, which are clan CD cysteine proteases. The inhibitors have secondorder rate constants of up to 104 M-1s -1 with pig kidney legumain and IC50 values as low as 45 nM with S. mansoni legumain. The most potent epoxides contain an ester moiety with S,S stereochemistry attached to the epoxide. Interestingly, amide and amino acid derivatives of the epoxysuccinate moiety were not inhibitors of legumain, while disubstituted amide derivatives are quite potent. The inhibitors have little or no inhibitory activity with other proteases such as caspases, chymotrypsin, papain, cathepsin B, granzyme B, and various aspartyl proteases.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
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- Substrate Specificity of Glutaminyl Cyclases from Plants and Animals
- The Binding of Haptoglobin to Apolipoprotein AI: Influence of Hemoglobin and Concanavalin A
- A Novel Water-Soluble and Cell-Permeable Calpain Inhibitor Protects Myocardial and Mitochondrial Function in Postischemic Reperfusion
- Potent Bivalent Inhibition of Human Tryptase-? by a Synthetic Inhibitor
- Aza-Peptide Epoxides: Potent and Selective Inhibitors of Schistosoma mansoni and Pig Kidney Legumains (Asparaginyl Endopeptidases)
- Semisynthesis and Application of Carboxyfluorescein-Labelled Biologically Active Human Interleukin-8
- Acknowledgment
- Content Index
- Author Index
- Subject Index
Articles in the same Issue
- Metabolic Stability, Receptor Binding, cAMP Generation, Insulin Secretion and Antihyperglycaemic Activity of Novel N-Terminal Glu9-Substituted Analogues of Glucagon-Like Peptide-1
- Characterisation of Human Dipeptidyl Peptidase IV Expressed in Pichia pastoris. A Structural and Mechanistic Comparison between the Recombinant Human and the Purified Porcine Enzyme
- Effects of Iron Limitation on the Respiratory Chain and the Membrane Cytochrome Pattern of the Euryarchaeon Halobacterium salinarum
- Anti-Mouse GPI-PLD Antisera Highlight Structural Differences between Murine and Bovine GPI-PLDs
- Substrate Specificity of Glutaminyl Cyclases from Plants and Animals
- The Binding of Haptoglobin to Apolipoprotein AI: Influence of Hemoglobin and Concanavalin A
- A Novel Water-Soluble and Cell-Permeable Calpain Inhibitor Protects Myocardial and Mitochondrial Function in Postischemic Reperfusion
- Potent Bivalent Inhibition of Human Tryptase-? by a Synthetic Inhibitor
- Aza-Peptide Epoxides: Potent and Selective Inhibitors of Schistosoma mansoni and Pig Kidney Legumains (Asparaginyl Endopeptidases)
- Semisynthesis and Application of Carboxyfluorescein-Labelled Biologically Active Human Interleukin-8
- Acknowledgment
- Content Index
- Author Index
- Subject Index
