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BioAssay: AID 499041

Inhibition of alpha-synuclein-mediated toxicity in yeast transfected with human alpha-synuclein by spotting assay

Phage display has demonstrated the utility of cyclic peptides as general protein ligands but cannot access proteins inside eukaryotic cells. Expanding a new chemical genetics tool, we describe the first expressed library of head-to-tail cyclic peptides in yeast (Saccharomyces cerevisiae). We applied the library to selections in a yeast model of alpha-synuclein toxicity that recapitulates much of more ..
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 Tested Compounds
 Tested Compounds
All(4)
 
 
Active(4)
 
 
 Tested Substances
 Tested Substances
All(4)
 
 
Active(4)
 
 
AID: 499041
Data Source: ChEMBL (649081)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2011-02-25
Modify Date: 2014-08-24

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Alpha-synuclein; AltName: Full=Non-A beta component of AD amyloid; AltName: Full=Non-A4 component of amyloid precursor; Short=NACP
Description ..   
Protein Family: Synuclein
Comment ..   

Gene:SNCA     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 4
Description:
Title: Rapid selection of cyclic peptides that reduce alpha-synuclein toxicity in yeast and animal models.

Abstract: Phage display has demonstrated the utility of cyclic peptides as general protein ligands but cannot access proteins inside eukaryotic cells. Expanding a new chemical genetics tool, we describe the first expressed library of head-to-tail cyclic peptides in yeast (Saccharomyces cerevisiae). We applied the library to selections in a yeast model of alpha-synuclein toxicity that recapitulates much of the cellular pathology of Parkinson's disease. From a pool of 5 million transformants, we isolated two related cyclic peptide constructs that specifically reduced the toxicity of human alpha-synuclein. These expressed cyclic peptide constructs also prevented dopaminergic neuron loss in an established Caenorhabditis elegans Parkinson's model. This work highlights the speed and efficiency of using libraries of expressed cyclic peptides for forward chemical genetics in cellular models of human disease.
(PMID: 19597508)
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Inhibition activity commentInhibition activity commentString
2Inhibition standard flagInhibition standard flagInteger
3Inhibition qualifierInhibition qualifierString
4Inhibition published valueInhibition published valueFloat
5Inhibition standard valueInhibition standard valueFloat

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
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