title: Helix stabilized, thermostable, and protease-resistant self-assembled peptide nanostructures as potential inhibitors of protein-protein interactions.
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.
authors.affiliation: Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.
authors.forename: Woo-jin
authors.initials: WJ
authors.lastname: Jeong
authors.forename: Myeong Sup
authors.initials: MS
authors.lastname: Lee
authors.forename: Yong-beom
authors.initials: YB
authors.lastname: Lim
mesh_terms: D000595:Amino Acid Sequence; D002918:Chymotrypsin / Q000737:chemistry; D002942:Circular Dichroism; D006207:Half-Life; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D049329:Nanostructures / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D059748:Proteolysis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
chemical_list: D010446:Peptide Fragments; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D002918:Chymotrypsin