Document Detail


Nanosensing protein allostery using a bivalent mouse double minute two (MDM2) assay.
MedLine Citation:
PMID:  22556265     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The tumor suppressor protein, p53, is either mutated or absent in >50% of cancers and is negatively regulated by the mouse double minute (MDM2) protein. Understanding and inhibition of the MDM2-p53 interaction are, therefore, critical for developing novel chemotherapeutics, which are currently limited because of a lack of appropriate study tools. We present a nanosensing approach to investigate full-length MDM2 interactions with p53, thus providing an allosteric assay for identifying binding ligands. Surface-enhanced Raman scattering (SERS)-active nanoparticles, functionalized with a p53 peptide mimic (peptide 12.1), display biologically specific aggregation following addition of MDM2. Nanoparticle assembly is competitively inhibited by the N-terminal MDM2-binding ligands peptide 12.1 and Nutlin-3. This study reports nanoparticle assembly through specific protein-peptide interactions that can be followed by SERS. We demonstrate solution-based MDM2 allosteric interaction studies that use the full-length protein.
Authors:
Anna F Robson; Ted R Hupp; Fiona Lickiss; Kathryn L Ball; Karen Faulds; Duncan Graham
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-03
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-23     Completed Date:  2012-08-02     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8073-8     Citation Subset:  IM    
Affiliation:
Centre for Molecular Nanometrology, WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Allosteric Regulation
Animals
Biosensing Techniques / methods*
Carrier Proteins / chemistry*,  metabolism*
Dimerization
Drug Design
Metal Nanoparticles / chemistry
Mice
Nanotechnology / methods*
Neoplasms / diagnosis,  metabolism
Protein Binding / physiology
Protein Interaction Domains and Motifs / physiology
Silver / chemistry
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Spectrum Analysis, Raman / methods*
Tumor Suppressor Protein p53 / metabolism
Grant Support
ID/Acronym/Agency:
//Biotechnology and Biological Sciences Research Council; //Cancer Research UK
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Mtbp protein, mouse; 0/Tumor Suppressor Protein p53; 7440-22-4/Silver
Comments/Corrections

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