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Reactivation of the p53 Tumor Suppressor Pathway by a Stapled p53 Peptide
Open accessAbstract
The p53-hDM2 protein interaction is a validated therapeutic target in cancer. We report the synthesis of stabilized alpha-helix of p53 (SAH-p53) compounds that antagonize the p53-hDM2 interaction. We demonstrate that hydrocarbon stapling confers cellular permeability to a p53 peptide that is then capable of modulating transcriptional activity. The lead SAH-p53 compound triggers apoptosis in hDM2-overexpressing cancer cells by reactivating the native p53 signaling pathway. SAH-p53 is the first example of an all-hydrocarbon i, i+ 7 stabilized peptide that subverts cancer through direct modulation of a transcriptional pathway.
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Citations
Cites
p53 Mutations in Human Cancers
Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991) · Science · doi:10.1126/science.1905840 · Cited by 8,018
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661
Momand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90644-r · Cited by 3,113
Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain
Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.948 · Cited by 2,206
Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
Honda, R., Tanaka, H., & Yasuda, H. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01480-4 · Cited by 1,951
Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix
Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., Wagner, G., Verdine, G. L., & Korsmeyer, S. J. (2004) · Science · doi:10.1126/science.1099191 · Cited by 1,349
Self-citationSchafmeister, C. E., Po, J., & Verdine, G. L. (2000) · Journal of the American Chemical Society · doi:10.1021/ja000563a · Cited by 1,037
Self-citationMono- Versus Polyubiquitination: Differential Control of p53 Fate by Mdm2
Li, M., Brooks, C. L., Wu-Baer, F., Chen, D., Baer, R., & Gu, W. (2003) · Science · doi:10.1126/science.1091362 · Cited by 804
Inhibiting the p53–MDM2 interaction: an important target for cancer therapy
Chène, P. (2003) · Nature Reviews Cancer · doi:10.1038/nrc991 · Cited by 765
Redistribution of Intracellular Oxygen in Hypoxia by Nitric Oxide: Effect on HIF1α
Hagen, T., Taylor, C. T., Lam, F., & Moncada, S. (2003) · Science · doi:10.1126/science.1088805 · Cited by 704
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Awakening guardian angels: drugging the p53 pathway
Brown, C. J., Lain, S., Verma, C. S., Fersht, A. R., & Lane, D. P. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2763 · Cited by 881
Drugging the p53 pathway: understanding the route to clinical efficacy
Khoo, K. H., Verma, C. S., & Lane, D. P. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4236 · Cited by 719
Pelay‐Gimeno, M., Glas, A., Koch, O., & Grossmann, T. N. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201412070 · Cited by 717
Strategic Approaches to Optimizing Peptide ADME Properties
Di, L. (2015) · The AAPS Journal · doi:10.1208/s12248-014-9687-3 · Cited by 669
Peptide stapling techniques based on different macrocyclisation chemistries
Lau, Y. H., de Andrade, P., Wu, Y., & Spring, D. R. (2015) · Chemical Society Reviews · doi:10.1039/c4cs00246f · Cited by 586
Modulators of Protein–Protein Interactions
Milroy, L.-G., Grossmann, T. N., Hennig, S., Brunsveld, L., & Ottmann, C. (2014) · Chemical Reviews · doi:10.1021/cr400698c · Cited by 497
Stapled Peptides for Intracellular Drug Targets
Verdine, G. L., & Hilinski, G. J. (2012) · Methods in Enzymology · doi:10.1016/b978-0-12-396962-0.00001-x · Cited by 433
Self-citationNew Modalities for Challenging Targets in Drug Discovery
Valeur, E., Guéret, S. M., Adihou, H., Gopalakrishnan, R., Lemurell, M., Waldmann, H., Grossmann, T. N., & Plowright, A. T. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201611914 · Cited by 382
Translating p53 into the clinic
Cheok, C. F., Verma, C. S., Baselga, J., & Lane, D. P. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.174 · Cited by 381
Synthesis of all-hydrocarbon stapled α-helical peptides by ring-closing olefin metathesis
Kim, Y.-W., Grossmann, T. N., & Verdine, G. L. (2011) · Nature Protocols · doi:10.1038/nprot.2011.324 · Cited by 376
Self-citationHydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic
Bird, G. H., Madani, N., Perry, A. F., Princiotto, A. M., Supko, J. G., He, X., Gavathiotis, E., Sodroski, J. G., & Walensky, L. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002713107 · Cited by 347
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Stiles, C. D., & Rowitch, D. H. (2008) · Neuron · doi:10.1016/j.neuron.2008.05.031 · Cited by 330
MDM4 is a key therapeutic target in cutaneous melanoma
Gembarska, A., Luciani, F., Fedele, C., Russell, E. A., Dewaele, M., Villar, S., Zwolinska, A., Haupt, S., de Lange, J., Yip, D., et al. (2012) · Nature Medicine · doi:10.1038/nm.2863 · Cited by 327
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Hydrocarbon Stapled Peptides as Modulators of Biological Function
Cromm, P. M., Spiegel, J., & Grossmann, T. N. (2015) · ACS Chemical Biology · doi:10.1021/cb501020r · Cited by 290
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Nevola, L., & Giralt, E. (2015) · Chemical Communications · doi:10.1039/c4cc08565e · Cited by 289
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Uversky, V. N., Davé, V., Iakoucheva, L. M., Malaney, P., Metallo, S. J., Pathak, R. R., & Joerger, A. C. (2014) · Chemical Reviews · doi:10.1021/cr400713r · Cited by 288
Contemporary strategies for the stabilization of peptides in the α-helical conformation
Henchey, L. K., Jochim, A. L., & Arora, P. S. (2008) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2008.08.019 · Cited by 288
A Stapled p53 Helix Overcomes HDMX-Mediated Suppression of p53
Bernal, F., Wade, M., Godes, M., Davis, T. N., Whitehead, D. G., Kung, A. L., Wahl, G. M., & Walensky, L. D. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.10.024 · Cited by 285
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Grossmann, T. N., Yeh, J. T.-H., Bowman, B. R., Chu, Q., Moellering, R. E., & Verdine, G. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208396109 · Cited by 268
Self-citationMDM2 and MDM4: p53 regulators as targets in anticancer therapy
Toledo, F., & Wahl, G. M. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.03.022 · Cited by 261
Structure of the Stapled p53 Peptide Bound to Mdm2
Baek, S., Kutchukian, P. S., Verdine, G. L., Huber, R., Holak, T. A., Lee, K. W., & Popowicz, G. M. (2012) · Journal of the American Chemical Society · doi:10.1021/ja2090367 · Cited by 259
Self-citationDual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia
Carvajal, L. A., Neriah, D. B., Senecal, A., Benard, L., Thiruthuvanathan, V., Yatsenko, T., Narayanagari, S.-R., Wheat, J. C., Todorova, T. I., Mitchell, K., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aao3003 · Cited by 249
Design and Structure of Stapled Peptides Binding to Estrogen Receptors
Phillips, C., Roberts, L. R., Schade, M., Bazin, R., Bent, A., Davies, N. L., Moore, R., Pannifer, A. D., Pickford, A. R., Prior, S. H., et al. (2011) · Journal of the American Chemical Society · doi:10.1021/ja202946k · Cited by 247
Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics
Ding, Y., Ting, J. P., Liu, J., Al-Azzam, S., Pandya, P., & Afshar, S. (2020) · Amino Acids · doi:10.1007/s00726-020-02890-9 · Cited by 200
How Chemoproteomics Can Enable Drug Discovery and Development
Moellering, R. E., & Cravatt, B. F. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.01.001 · Cited by 182
Peptides As Therapeutics with Enhanced Bioactivity
Goodwin, D., Simerska, P., & Toth, I. (2012) · Current Medicinal Chemistry · doi:10.2174/092986712803251548 · Cited by 176
Phan, J., Li, Z., Kasprzak, A., Li, B., Sebti, S., Guida, W., Schönbrunn, E., & Chen, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.073056 · Cited by 173
Targeting Mdm2 and Mdmx in cancer therapy: better living through medicinal chemistry?
Wade, M., & Wahl, G. M. (2009) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-08-0423 · Cited by 170
The role of ubiquitin modification in the regulation of p53
Hock, A. K., & Vousden, K. H. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.05.022 · Cited by 168
Saleh, M. N., Patel, M. R., Bauer, T. M., Goel, S., Falchook, G. S., Shapiro, G. I., Chung, K. Y., Infante, J. R., Conry, R. M., Rabinowits, G., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0715 · Cited by 159
A Left‐Handed Solution to Peptide Inhibition of the p53–MDM2 Interaction
Liu, M., Pazgier, M., Li, C., Yuan, W., Li, C., & Lu, W. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.201000329 · Cited by 115
Pharmacological reactivation of p53 as a strategy to treat cancer
Zawacka‐Pankau, J., & Selivanova, G. (2015) · Journal of Internal Medicine · doi:10.1111/joim.12336 · Cited by 82
Translational approaches targeting the p53 pathway for anti‐cancer therapy
Essmann, F., & Schulze‐Osthoff, K. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01570.x · Cited by 77
Meek, D. W., & Hupp, T. R. (2010) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2009.10.005 · Cited by 76
Plucking the high hanging fruit: A systematic approach for targeting protein–protein interactions
Raj, M., Bullock, B. N., & Arora, P. S. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2012.11.023 · Cited by 66
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Zhang, Z., Ding, Q., Liu, J.-J., Zhang, J., Jiang, N., Chu, X.-J., Bartkovitz, D., Luk, K.-C., Janson, C., Tovar, C., et al. (2014) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2014.05.072 · Cited by 60
Inhibition of Wild-Type p53-Expressing AML by the Novel Small Molecule HDM2 Inhibitor CGM097
Weisberg, E., Halilovic, E., Cooke, V. G., Nonami, A., Ren, T., Sanda, T., Simkin, I., Yuan, J., Antonakos, B., Barys, L., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0429 · Cited by 56
Hahne, G., & Grossmann, T. N. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2013.02.050 · Cited by 46
Targeted covalent inhibitors of MDM2 using electrophile-bearing stapled peptides
Charoenpattarapreeda, J., Tan, Y. S., Iegre, J., Walsh, S. J., Fowler, E., Eapen, R. S., Wu, Y., Sore, H. F., Verma, C. S., Itzhaki, L., et al. (2019) · Chemical Communications · doi:10.1039/c9cc04022f · Cited by 35
p53: from understanding its structure to advances in therapeutic targeting
Wang, W., Liu, X., Liu, H., Abolhassani, H., Yan, H., Zhang, H., & Wang, X. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02549-5 · Cited by 30
Unprotected peptide macrocyclization and stapling via a fluorine-thiol displacement reaction
Islam, M. S., Junod, S. L., Zhang, S., Buuh, Z. Y., Guan, Y., Zhao, M., Kaneria, K. H., Kafley, P., Cohen, C., Maloney, R., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-27995-5 · Cited by 28
A general synthesis of dirhodium metallopeptides as MDM2 ligands
Zaykov, A. N., & Ball, Z. T. (2011) · Chemical Communications · doi:10.1039/c1cc13169a · Cited by 27
Muppidi, A., Li, X., Chen, J., & Lin, Q. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.10.009 · Cited by 16
Metadata
- Authors
- Bernal, F., Tyler, A. F., Korsmeyer, S. J., Walensky, L. D., & Verdine, G. L.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-02-07
- Volume
- 129
- Issue
- 9
- Pages
- 2456-2457
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2079945282
- Cited by
- 556
- References
- 11
- FWCI
- 10.30
- Type
- journal article
- Language
- en
- Open access
- green
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