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. 2007 Mar 7;129(9):2456-7.
doi: 10.1021/ja0693587. Epub 2007 Feb 7.

Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide

Federico Bernal  1 , Andrew F Tyler, Stanley J Korsmeyer, Loren D Walensky, Gregory L Verdine
Affiliations

Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide

Federico Bernal et al. J Am Chem Soc. .

Erratum in

  • J Am Chem Soc. 2007 Apr 25;129(16):5298
No abstract available

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Figures

Figure 1.
Figure 1.
Synthesis, sequence, and biochemical analysis of SAH-p53 peptides. (A) Non-natural amino acids were synthesized as described and cross-linked by ruthenium-catalyzed ring-closing olefin metathesis. (B) SAH-p53 compounds were generated by stapling the p5314-29 sequence at the indicated positions. Charge, α-helicity, hDM2 binding affinity, cell permeability, and impact on cell viability are indicated for each compound. (C, E) Circular dichroism spectra revealed enhancement of α-helicity for SAH-p53 compounds. (D, F) Fluorescence polarization assays using FITC-peptides and hDM217-125 demonstrated subnanomolar hDM2-binding affinities for select SAH-p53 peptides. Note: UAH-p53-8 is the “unstapled” form of SAH-p53-8.
Figure 2.
Figure 2.
SAH-p53-8 reactivates the p53 transcriptional pathway. The hDM2 overexpressing SJSA-1 cells were exposed to the indicated peptides, and Western analyses for p53, hDM2, and p21 were performed at 8–30 h of treatment.
Figure 3.
Figure 3.
Reactivation of apoptosis in SAH-p53-8-treated SJSA-1 cells. SAH-p53-8 demonstrated specific, dose-dependent cytotoxicity and apoptosis induction as measured by (A) CellTiter-Glo (Promega) and (B) Caspase-3 activation assays (Oncogene).
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