Nanosensing protein allostery using a bivalent mouse double minute two (MDM2) assay

Anna F. Robson, Ted R. Hupp, Fiona Lickiss, Kathryn L. Ball, Karen Faulds, Duncan Graham

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages8073-8078
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume109
Issue number21
DOIs
Publication statusPublished - 22 May 2012

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Nanoparticles
Peptides
Raman Spectrum Analysis
Proteins
Ligands
Tumor Suppressor Protein p53
Neoplasms
nutlin 3

Keywords

  • nanosensing
  • protein allostery
  • bivalent mouse

Cite this

Robson, Anna F. ; Hupp, Ted R. ; Lickiss, Fiona ; Ball, Kathryn L. ; Faulds, Karen ; Graham, Duncan. / Nanosensing protein allostery using a bivalent mouse double minute two (MDM2) assay. In: Proceedings of the National Academy of Sciences . 2012 ; Vol. 109, No. 21. pp. 8073-8078.
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Nanosensing protein allostery using a bivalent mouse double minute two (MDM2) assay. / Robson, Anna F.; Hupp, Ted R.; Lickiss, Fiona; Ball, Kathryn L.; Faulds, Karen; Graham, Duncan.

In: Proceedings of the National Academy of Sciences , Vol. 109, No. 21, 22.05.2012, p. 8073-8078.

Research output: Contribution to journalArticle

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