Arecoline Tripeptide Inhibitors of Proteasome
- 10 February 2004
- journal article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 47 (6), 1587-1590
- https://doi.org/10.1021/jm0309102
Abstract
The 26S proteasome is a multicatalytic protease complex that plays an essential role in intracellular protein degradation. We have synthesized and tested a series of arecoline peptide derivatives where the peptide portion derives from a screening of tripeptide sequences, and the arecoline moiety has been considered as a potential substrate for catalytic threonine. Derivatives 17−19 are the best compounds of the series, showing chymotryptic-like (β5) inhibition (IC50 ≅ 1 μM) and favorable pharmacokinetic properties.Keywords
This publication has 16 references indexed in Scilit:
- Proteasome inhibitors reconstitute the presentation of cytotoxic T‐cell epitopes in Epstein‐Barr virus–associated tumorsInternational Journal of Cancer, 2002
- Towards subunit-specific proteasome inhibitors: synthesis and evaluation of peptide α', β'-epoxyketonesCell Chemical Biology, 1999
- The role of the ubiquitin-proteasome pathway in apoptosisCell Death & Differentiation, 1999
- Bifunctional inhibitors of the trypsin-like activity of eukaryotic proteasomesCell Chemical Biology, 1999
- Lactacystin and clasto-Lactacystin β-Lactone Modify Multiple Proteasome β-Subunits and Inhibit Intracellular Protein Degradation and Major Histocompatibility Complex Class I Antigen PresentationJournal of Biological Chemistry, 1997
- Potent α-ketocarbonyl and boronic ester derived inhibitors of proteasomeBioorganic & Medicinal Chemistry Letters, 1996
- Potent Inhibitors of ProteasomeJournal of Medicinal Chemistry, 1995
- The ubiquitin-proteasome proteolytic pathwayCell, 1994
- The human multicatalytic proteinase: affinity purification using a monoclonal antibodyJournal of Biochemical and Biophysical Methods, 1991
- Involvement of the proteasome in various degradative processes in mammalian cells.Proceedings of the National Academy of Sciences, 1989