Discovery and Development of Cyclic Peptide Proteasome Stimulators
Abstract: The proteasome degrades proteins, which is essential for cellular homeostasis. Ubiquitin independent proteolysis degrades highly disordered and misfolded proteins. A decline of proteasomal activity has been associated with multiple neurodegenerative diseases due to the accumulation of misfolded proteins. In this work, cyclic peptide proteasome stimulators (CyPPSs) that enhance the clearance of misfolded proteins were discovered. In the initial screen of predicted natural products (pNPs), several cyclic peptides were found to stimulate the 20S core particle (20S CP). Development of a robust structural activity relationship led to the identification of potent, cell permeable CyPPSs. In vitro assays revealed that CyPPSs stimulate degradation of highly disordered and misfolded proteins without affecting ordered proteins. Furthermore, using a novel flow‐based assay for proteasome activity, several CyPPSs were found to stimulate the 20S CP in cellulo. Overall, this work describes the development of CyPPSs as chemical tools capable of stimulating the proteasome and provides strong support for proteasome stimulation as a therapeutic strategy for neurodegenerative diseases.
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Bibliographic citation
-
Discovery and Development of Cyclic Peptide Proteasome Stimulators ; day:15 ; month:12 ; year:2023 ; extent:8
ChemBioChem ; (15.12.2023) (gesamt 8)
- Creator
-
Nelson, Samantha
Harris, Timothy J.
Muli, Christine S.
Maresh, Marianne E.
Baker, Braden
Smith, Chloe
Neumann, Chris
Trader, Darci J.
Parkinson, Elizabeth I.
- DOI
-
10.1002/cbic.202300671
- URN
-
urn:nbn:de:101:1-2023121614141151412303
- Rights
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
15.08.2025, 7:20 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Nelson, Samantha
- Harris, Timothy J.
- Muli, Christine S.
- Maresh, Marianne E.
- Baker, Braden
- Smith, Chloe
- Neumann, Chris
- Trader, Darci J.
- Parkinson, Elizabeth I.
Other Objects (12)
Chlorofusin Cyclic Peptide Synthesis
Discovery and Characterization of Novel Proteasome Ligand Binding Sites
Peptide and Peptide-Like Modulators of 20S Proteasome Enzymatic Activity in Cancer Cells
Targeted Discovery of Tetrapeptides and Cyclic Polyketide‐Peptide Hybrids from a Fungal Antagonist of Farming Termites
Sequence-optimized peptide nanofibrils as growth stimulators for regeneration of peripheral neurons
Cyclic Peptide Synthesis Using Peptidyl Salicylaldehyde Esters
Modelling water molecules inside cyclic peptide nanotubes
Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis
Pflanzliche Stimulatoren der Sexualfunktion
Mode als Stimulator : Bekleidung
The Development of a Fluorescence‐Based Competitive Assay Enabled the Discovery of Dimeric Cyclic Peptide Modulators of Ubiquitin Chains
The Development of a Fluorescence‐Based Competitive Assay Enabled the Discovery of Dimeric Cyclic Peptide Modulators of Ubiquitin Chains
Chlorofusin Cyclic Peptide Synthesis
Discovery and Characterization of Novel Proteasome Ligand Binding Sites
Peptide and Peptide-Like Modulators of 20S Proteasome Enzymatic Activity in Cancer Cells
Targeted Discovery of Tetrapeptides and Cyclic Polyketide‐Peptide Hybrids from a Fungal Antagonist of Farming Termites
Sequence-optimized peptide nanofibrils as growth stimulators for regeneration of peripheral neurons
Cyclic Peptide Synthesis Using Peptidyl Salicylaldehyde Esters
Modelling water molecules inside cyclic peptide nanotubes
Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis
Pflanzliche Stimulatoren der Sexualfunktion
Mode als Stimulator : Bekleidung
The Development of a Fluorescence‐Based Competitive Assay Enabled the Discovery of Dimeric Cyclic Peptide Modulators of Ubiquitin Chains
The Development of a Fluorescence‐Based Competitive Assay Enabled the Discovery of Dimeric Cyclic Peptide Modulators of Ubiquitin Chains
Chlorofusin Cyclic Peptide Synthesis
Discovery and Characterization of Novel Proteasome Ligand Binding Sites
Peptide and Peptide-Like Modulators of 20S Proteasome Enzymatic Activity in Cancer Cells
Targeted Discovery of Tetrapeptides and Cyclic Polyketide‐Peptide Hybrids from a Fungal Antagonist of Farming Termites
Sequence-optimized peptide nanofibrils as growth stimulators for regeneration of peripheral neurons
Cyclic Peptide Synthesis Using Peptidyl Salicylaldehyde Esters
Modelling water molecules inside cyclic peptide nanotubes
Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis
Pflanzliche Stimulatoren der Sexualfunktion
Mode als Stimulator : Bekleidung
The Development of a Fluorescence‐Based Competitive Assay Enabled the Discovery of Dimeric Cyclic Peptide Modulators of Ubiquitin Chains