Polymer-Supported Approach for Solution-Phase Synthesis of Cysteine Trap Protease Inhibitors: Procedure for Straightforward Optimization of the P1−P1‘ Pocket
- 11 December 2001
- journal article
- Published by American Chemical Society (ACS) in Journal of Combinatorial Chemistry
- Vol. 4 (1) , 49-55
- https://doi.org/10.1021/cc010037v
Abstract
Peptide-based reversible and irreversible cysteine proteases inhibitors are well reported in the literature. Many of these compounds have an electrophilic carbonyl group as a cysteine trap in the place of a scissile amide moiety of the natural substrate. As a common mechanism strategy, we have designed a probe library of a cysteine trap for rapid optimization of P1−P1‘ pockets of different cysteine proteases. The synthesis of this library using a straightforward methodology based on polymer-supported reagents and scavengers to avoid tedious purification steps has been achieved. For the selective monobromination of diazo ketones, preparation of a new supported reagent, piperidinoaminomethylpolystyrene hydrobromide, is also described.Keywords
This publication has 11 references indexed in Scilit:
- On the size of the active site in proteases. I. PapainPublished by Elsevier ,2005
- Cathepsin K, but Not Cathepsins B, L, or S, Is Abundantly Expressed in Human OsteoclastsJournal of Biological Chemistry, 1996
- Inhibition of Human Neutrophil Elastase with Peptidyl Electrophilic Ketones. 2. Orally Active PG-Val-Pro-Val Pentafluoroethyl KetonesJournal of Medicinal Chemistry, 1994
- Cysteine Proteinase Inhibitors Decrease Articular Cartilage and Bone Destruction in Chronic Inflammatory ArthritisArthritis & Rheumatism, 1994
- Stereocontrolled Synthesis of Erythro N-Protected α-Amino Epoxides and Peptidyl Epoxides.Tetrahedron, 1994
- Inhibition studies of some serine and thiol proteinases by new leupeptin analogsJournal of Medicinal Chemistry, 1993
- Synthetic inhibitors of human neutrophil elastaseTrends in Pharmacological Sciences, 1987
- Synthesis of fluorinated α-amino ketones part I: α-benzamidoalkyl mono- di- and trifluoromethyl ketonesTetrahedron Letters, 1986
- Cysteine proteinases and metastasisCancer and Metastasis Reviews, 1984
- Lipid solubility and affinity for N-demethylation of dansylamides in isolated rat hepatocytesJournal of Medicinal Chemistry, 1976