Helix stabilized, thermostable, and protease-resistant self-assembled peptide nanostructures as potential inhibitors of protein-protein interactions

Woo Jin Jeong, Myeong Sup Lee, Yong-beom Lim

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Self-assembled peptide nanostructures with actively folded secondary structures have potential to mimic the function of proteins. We here show that α-helix-stabilized self-assembled peptide nanostructures (αSSPNs), whose sizes are comparable to those of proteins, have potential to be developed as protein-protein interaction (PPI) inhibitors along with several unprecedented properties. Using p53-MDM2 PPI as a model system, the molecular recognition and modulation of PPIs by αSSPN grafted with a p53 α-helix (p53 αSSPN) were investigated. The competition assay showed that the p53 αSSPN can inhibit the p53-MDM2 interaction. Interestingly, the p53 αSSPN was far more resistant to degradation by the protease chymotrypsin than the monomeric p53 peptide and had high thermal stability. These results suggest that the αSSPN scaffold holds great potential to be developed as a novel class of PPI inhibitors.

Original languageEnglish
Pages (from-to)2684-2689
Number of pages6
JournalBiomacromolecules
Volume14
Issue number8
DOIs
Publication statusPublished - 2013 Aug 12

Fingerprint

Peptides
Nanostructures
Peptide Hydrolases
Proteins
Molecular recognition
Chymotrypsin
Scaffolds (biology)
Scaffolds
Assays
Thermodynamic stability
Modulation
Degradation

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

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abstract = "Self-assembled peptide nanostructures with actively folded secondary structures have potential to mimic the function of proteins. We here show that α-helix-stabilized self-assembled peptide nanostructures (αSSPNs), whose sizes are comparable to those of proteins, have potential to be developed as protein-protein interaction (PPI) inhibitors along with several unprecedented properties. Using p53-MDM2 PPI as a model system, the molecular recognition and modulation of PPIs by αSSPN grafted with a p53 α-helix (p53 αSSPN) were investigated. The competition assay showed that the p53 αSSPN can inhibit the p53-MDM2 interaction. Interestingly, the p53 αSSPN was far more resistant to degradation by the protease chymotrypsin than the monomeric p53 peptide and had high thermal stability. These results suggest that the αSSPN scaffold holds great potential to be developed as a novel class of PPI inhibitors.",
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Helix stabilized, thermostable, and protease-resistant self-assembled peptide nanostructures as potential inhibitors of protein-protein interactions. / Jeong, Woo Jin; Lee, Myeong Sup; Lim, Yong-beom.

In: Biomacromolecules, Vol. 14, No. 8, 12.08.2013, p. 2684-2689.

Research output: Contribution to journalArticle

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