Cited by 403Cancer-related Molecular PathwaysProtein Structure and DynamicsChemical Synthesis and Analysis

The DOI matches its Crossref record; 51 of the 53 references it cites were found in a registry or an index.

Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX

Open access

Pazgier, Marzena, Liu, Min, Zou, Guozhang, Yuan, Weirong, Li, Changqing, Li, Chong, Li, Jing, Monbo, Juahdi, Zella, Davide, Tarasov, Sergey G., Lu, Wuyuan·2009·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0900947106PMC PMC2660734

Open this paper in CoChat — free account

Abstract

The oncoproteins MDM2 and MDMX negatively regulate the activity and stability of the tumor suppressor protein p53—a cellular process initiated by MDM2 and/or MDMX binding to the N-terminal transactivation domain of p53. MDM2 and MDMX in many tumors confer p53 inactivation and tumor survival, and are important molecular targets for anticancer therapy. We screened a duodecimal peptide phage library against site-specifically biotinylated p53-binding domains of human MDM2 and MDMX chemically synthesized via native chemical ligation, and identified several peptide inhibitors of the p53-MDM2/MDMX interactions. The most potent inhibitor (TSFAEYWNLLSP), termed PMI, bound to MDM2 and MDMX at low nanomolar affinities—approximately 2 orders of magnitude stronger than the wild-type p53 peptide of the same length (ETFSDLWKLLPE). We solved the crystal structures of synthetic MDM2 and MDMX, both in complex with PMI, at 1.6 Å resolution. Comparative structural analysis identified an extensive, tightened intramolecular H-bonding network in bound PMI that contributed to its conformational stability, thus enhanced binding to the 2 oncogenic proteins. Importantly, the C-terminal residue Pro of PMI induced formation of a hydrophobic cleft in MDMX previously unseen in the structures of p53-bound MDM2 or MDMX. Our findings deciphered the structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX, shedding new light on structure-based rational design of different classes of p53 activators for potential therapeutic use.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1073/pnas.0900947106

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features
Kabsch, W., & Sander, C. (1983) · Biopolymers · doi:10.1002/bip.360221211 · Cited by 15,320
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,796
Surfing the p53 network
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607
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
Mdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506
Synthesis of Proteins by Native Chemical Ligation
Dawson, P. E., Muir, T. W., Clark‐Lewis, I., & Kent, S. B. H. (1994) · Science · doi:10.1126/science.7973629 · Cited by 4,190
How to measure and predict the molar absorption coefficient of a protein
Pace, C., Vajdos, F., Fee, L. R., Grimsley, G., & Gray, T. (1995) · Protein Science · doi:10.1002/pro.5560041120 · Cited by 3,924
Regulation of p53 stability by Mdm2
Kubbutat, M. H. G., Jones, S. N., & Vousden, K. H. (1997) · Nature · doi:10.1038/387299a0 · Cited by 3,312 · cited 1×
“Growing evidence supports that in unstressed cells MDM2 primarily controls p53 stability through ubiquitylation to target the tumor suppressor protein for constitutive degradation by the proteasome (13, 14), whereas MDMX mainly functions as a significant p53 transcriptional antagonist independently of MDM2 (15, 16).”
Background
Live or let die: the cell's response to p53
Vousden, K. H., & Lü, X. (2002) · Nature reviews. Cancer · doi:10.1038/nrc864 · Cited by 3,231

Flagged first, then by citations

Show all 53 references

2 of the 53 references couldn’t be matched to a known paper.

Sorted by citations

Items 301–400 of 403

A Dual-Specificity d -Peptide Antagonist of MDM2 and MDMX for Antitumor Immunotherapy
Liao, C., Yan, J., Tolbert, W. D., Chen, X., Pazgier, M., Lu, W., Zhan, C., & Lu, W. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c02057 · Cited by 6
Self-citation
Decoding the Central Dogma: Quantitative Insights into Transcription and Translation Dynamics in the p53-Mediated DNA Damage Response
François, J., Jambhekar, A., & Lahav, G. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169436 · Cited by 4
Systematic mutational analysis of an ubiquitin ligase (MDM2)-binding peptide: computational studies
Liu, Y., Lane, D. P., & Verma, C. S. (2011) · Theoretical Chemistry Accounts · doi:10.1007/s00214-011-1049-y · Cited by 4
Peptide and protein chemistry approaches to study the tumor suppressor protein p53
Chatterjee, C., & Singh, S. K. (2022) · Organic & Biomolecular Chemistry · doi:10.1039/d2ob00902a · Cited by 4
Design and synthesis of novel cyclopeptide p53-MDM2 inhibitors with isoindolinone as antitumor agent
Zhao, L., Wei, L., Li, X., Chen, H., Liu, J., Wang, X., & Guan, F. (2022) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2022.134604 · Cited by 4
Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signaling axis
Zhou, T., Ke, Z., Ma, Q., Xiang, J., Gao, M., Huang, Y., Cheng, X., & Su, Z. (2023) · Scientific Reports · doi:10.1038/s41598-023-47808-z · Cited by 4
Multiplex peptide evolution via efficient solid-phase and side-chain guanidyl-construction
Wang, N., Chen, B., Li, Y., Li, X., & Hu, H. (2025) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2025.102651 · Cited by 4
The Mimic Chain Reaction
Norris, V., Thierry, A. R., Amar, P., Holland, I. B., & Molina, F. (2012) · Microbial Physiology · doi:10.1159/000345328 · Cited by 4
Structural Basis for α‐Helix Mimicry and Inhibition of Protein–Protein Interactions with Oligourea Foldamers
Cussol, L., Mauran, L., Buratto, J., Belorusova, A. Y., Neuville, M., Ősz, J., Fribourg, S., Frémaux, J., Dolain, C., Goudreau, S. R., et al. (2020) · Angewandte Chemie · doi:10.1002/ange.202008992 · Cited by 4
Generative Design of High-Affinity Peptides Using BindCraftPreprint
Filius, M., Patsos, T., Minnee, H., Turco, G., Liu, J., Gnatzy, M. T., Rooth, R. S. M., Liu, A. C. H., Ta, R. D. T., Rijk, I. H. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.23.666285 · Cited by 4
Cellular, Structural Basis, and Recent Progress for Targeting Murine Double Minute X (MDMX) in Tumors
Yin, Q., Hu, Y., Dong, Z., Lu, J., & Wang, H. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00913 · Cited by 3
Analysis and Prediction of Chymotrypsin Substrate Preferences through Large Data Acquisition with Target‐Free mRNA Display
Iskandar, S. E., Guan, L., Maini, R., Hipolito, C. J., Sun, C., Vasicek, L. A., Sindhikara, D., Weinglass, A. B., & Saldanha, S. A. (2024) · ChemBioChem · doi:10.1002/cbic.202400760 · Cited by 3
Reengineering of a Proteomimetic Pan‐Ras Inhibitor into a Ras Degrader
Ongkingco, J. F., Hong, S. H., Toth, E. D., Nguyễn, T. T., & Arora, P. S. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202507092 · Cited by 4
A Quantitative Systems Approach to Define Novel Effects of Tumour p53 Mutations on Binding Oncoprotein MDM2
Fuentes, M., Srivastava, S., Gronenborn, A. M., & LaBaer, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010053 · Cited by 3
Peptide‑based therapeutic strategies for glioma: Current state and prospects
Mi, Y., Jiang, P., Luan, J., Feng, L., Zhang, D., & Gao, X. (2025) · Peptides · doi:10.1016/j.peptides.2025.171354 · Cited by 3
Interchain doubly-bridged α-helical peptides for the development of protein binders
Chen, Y., Liang, J., Li, T., Lin, P. J., Zhao, Y., & Wu, C. (2019) · Chinese Chemical Letters · doi:10.1016/j.cclet.2019.02.013 · Cited by 3
Interactions of HIV-1 Proteins as Targets for Developing Anti-HIV-1 Peptides
Chandra, K., Maes, M., & Friedler, A. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.15.46 · Cited by 3
Insight into binding modes of p53 and inhibitors to MDM2 based on molecular dynamic simulations and principal component analysis
Cheng, W.-Y., Liang, Z., Wang, W., Yi, C., Li, H., Zhang, S., & Zhang, Q. (2015) · Molecular Physics · doi:10.1080/00268976.2015.1087598 · Cited by 3
P53-MDM2 interaction monitoring and inhibitors potency evaluation based on CRISPR-Cas12a sensing platform
Zhu, M., Pan, J., Xu, M., Cao, J., Zhu, Y., Zhu, H., Su, G., & Yu, Y. (2022) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2022.131710 · Cited by 3
Intracellular Targeting of Cyclotides for Therapeutic Applications
Lawrence, N., & Craik, D. J. (2021) · Methods in pharmacology and toxicology · doi:10.1007/978-1-0716-1250-7_11 · Cited by 3
An adeno-associated virus vector-based intracellular peptide delivery system for treating hepatocellular carcinoma with wild-type p53
Qie, B., Li, J., Wan, M., & Zhu, Y. (2025) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2025.126298 · Cited by 2
Self-citation
p53-Reactivating Molecules as Research Tools and Anticancer Drugs
Grinkevich, V. V., Warnecke, A., & Selivanova, G. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3676-8_13 · Cited by 2
Merging the Isonitrile‐Tetrazine (4+1) Cycloaddition and the Ugi Four‐Component Reaction into a Single Multicomponent Process
Méndez, Y., Vasco, A. V., Ivey, G., Dias, A. L., Gierth, P. T., Sousa, B. B., Navo, C. D., Torres-Mozas, Á., Rodrigues, T., Jiménez‐Osés, G., et al. (2023) · Angewandte Chemie · doi:10.1002/ange.202311186 · Cited by 2
Structural Adaptation of Secondary P53 Binding Sites on Mdm2 and Mdmx
Higbee, P. S., Dayhoff, G. W., Anbanandam, A., Varma, S., & Daughdrill, G. W. (2024) · Journal of Molecular Biology · doi:10.1016/j.jmb.2024.168626 · Cited by 2
Designer polyQ fusion proteins sequester USP7/HDM2 for modulating P53 functionality
Zhang, X., Yue, H.-W., Liu, Y., Wang, J., Duan, H.-T., Liu, Y.-H., Jiang, L., & Hu, H. (2025) · iScience · doi:10.1016/j.isci.2025.112025 · Cited by 3
Discovery of a Phenylalanine‐Derived Natural Compound as a Potential Dual Inhibitor of MDM2 and MDMX
Cho, J. Y., Park, S., Kim, T., Eom, J., Rho, J., & Bai, H. (2025) · ChemMedChem · doi:10.1002/cmdc.202500397 · Cited by 2
Rational design and selection of next-generation cyclotide drugs using the knotted cyclic peptide scaffold MCoTI-II
Ullrich, S., Philippe, G. J.-B., Li, C. Y., & Suga, H. (2025) · Australian Journal of Chemistry · doi:10.1071/ch25086 · Cited by 2
Self-citation
A biocatalytic peptidobiosensing molecular bridge for detecting osteosarcoma marker protein
Jing, P., Wang, Y., Sun, W., Li, G., Zhang, Z., Xu, Q., & Li, H. (2023) · Frontiers in Chemistry · doi:10.3389/fchem.2022.1112111 · Cited by 2
Mimicking a p53‐MDM2 interaction based on a stable immunoglobulin‐like domain scaffold
Jiménez‐Sandoval, P., Madrigal‐Carrillo, E. A., Santamaría‐Suárez, H. A., Maturana, D., Rentería‐González, I., Benítez‐Cardoza, C. G., Torres‐Larios, A., & Brieba, L. G. (2018) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.25519 · Cited by 2
Thrombopoietin receptor‐based protein–protein interaction screening (THROPPIS)
Horikawa, M., Kakiuchi, Y., Kashima, D., Ogawa, K., & Kawahara, M. (2021) · Biotechnology and Bioengineering · doi:10.1002/bit.27975 · Cited by 2
A small HDM2 antagonist peptide and a USP7 inhibitor synergistically inhibit the p53‐HDM2‐USP7 circuit
Mukherjee, S., Saha, G., Roy, N. S., Naiya, G., Ghosh, M. K., & Roy, S. (2023) · Chemical Biology & Drug Design · doi:10.1111/cbdd.14255 · Cited by 2
Evolution of KIPPIS as a versatile platform for evaluating intracellularly functional peptide aptamers
Kashima, D., & Kawahara, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-91287-z · Cited by 2
Generation of highly diverse peptide library by linear-double-stranded DNA based AND gate genetic circuit in mammalian cellsPreprint
Li, S., Su, W., & Zhang, C. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/392498 · Cited by 2
Dissecting the geometric and hydrophobic constraints of stapled peptides
Li, J., Tan, Y. S., & Verma, C. S. (2024) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26662 · Cited by 1
Self-citation
Guanidinium‐Stapled Helical Peptides for Targeting Protein‐Protein Interactions
Perdriau, C., Luton, A., Zimmeter, K., Neuville, M., Saragaglia, C., Peluso‐Iltis, C., Ősz, J., Kauffmann, B., Collie, G. W., Rochel, N., et al. (2024) · Angewandte Chemie · doi:10.1002/ange.202416348 · Cited by 1
Polyethylene glycol incorporation to reduce the cytotoxicity associated with cationic cell-penetrating-peptide conjugation
Umezawa, N., Arakawa, K., Kato, M., Hisamatsu, Y., Yagi, H., Miyajima, C., & Inoue, Y. (2025) · RSC Medicinal Chemistry · doi:10.1039/d5md00503e · Cited by 1
A General Synthesis Approach to Double‐Guanidinium Stapled Peptides and Foldamers
Neuville, M., Bornez, M. M., Bourgeais, M., Samueli, H., Mauran, L., Goudreau, S. R., Khatib, A., Guichard, G., & Pasco, M. (2025) · Chemistry - A European Journal · doi:10.1002/chem.202502273 · Cited by 3
FLASH-AWAY: Intrabody-Directed Targeting of Optogenetic Tools for Protein Degradation
Zhuang, Z., Li, R., Wang, B., Meng, Y., Li, Y., Nan, J., Zhao, X., & Ji, J. (2025) · ACS Synthetic Biology · doi:10.1021/acssynbio.4c00822 · Cited by 1
Reduced structural rigidity of MDMX protein enhances binding to TP53 mRNA
Kucerikova, M., Bonczek, O., Olivares‐Illana, V., Rodriguez-Rodriguez, A., Sampedro, J. G., Hernychová, L., Hrabal, V., Zatloukalová, P., Krejčíř, R., Fåhræus, R., et al. (2025) · Bioscience Reports · doi:10.1042/bsr20253646 · Cited by 1
De novo grafted coiled-coil peptides as p53/ h DM2 inhibitors
Spain, F., Giménez, D., Acevedo‐Jake, A. M., Mylemans, B., Brooks, N. J., Korona, B., Huang, D. T. C., Edwards, T. A., Leney, A. C., Itzhaki, L. S., et al. (2026) · RSC Chemical Biology · doi:10.1039/d6cb00063k · Cited by 1
Multivalent peptides displayed on OEGMA-based copolymers for the modulation of protein–protein interactions
Li, Y., Li, T., Wang, J., Bao, X., Zhao, Y., & Wu, C. (2015) · Polymer Chemistry · doi:10.1039/c5py01080b · Cited by 1
All about that Amide Bond: The Sixth Chemical Protein Synthesis (CPS) Meeting
Weller, C. E., & Chatterjee, C. (2015) · ChemBioChem · doi:10.1002/cbic.201500473 · Cited by 1
The facile and visualizable identification of broad-spectrum inhibitors of MDM2/p53 using co-expressed protein complexes
Yang, Y., Dong, Z., Hu, H., Peng, J., Sheng, Y., Yang, T., Yuan, S., Li, Z., Yang, J., Wells, T., et al. (2019) · The Analyst · doi:10.1039/c9an00350a · Cited by 1
Detecting ligand–protein interactions inside cells using reactive peptide tags and split luciferase
Takahashi, T., & Hagiwara, H. (2021) · Chemical Communications · doi:10.1039/d1cc03556h · Cited by 1
In silico design of anti-tumor mini-protein targeting MDM2
Zhang, J., Xu, H., Wang, B., Zhang, X., Fu, L., Li, Y., Wu, G., Zhao, Z., Liu, L., Yang, T., et al. (2022) · Chinese Chemical Letters · doi:10.1016/j.cclet.2022.107871 · Cited by 2
Design, synthesis, and anti-tumor activity of cyclic peptide–lenalidomide conjugated small molecules
Li, T., Li, T., Zhang, X., Xu, H., Xie, Y., Yan, R., Wu, X., Jin, Y., & Wang, Z. (2024) · New Journal of Chemistry · doi:10.1039/d3nj05320b · Cited by 1
Assembly of Glycopeptides in Living Cells Resembling Viral Infection for Cargo Delivery
Tian, F., Guo, R., Wu, C., Liu, X., Zhang, Z., Wang, Y., Wang, H., Li, G., & Yu, Z. (2024) · Angewandte Chemie · doi:10.1002/ange.202404703 · Cited by 1
Translation of Deoxyribonucleic Acid into Synthetic Alpha Helical Peptides for Darwinian Evolution
Dockerill, M., Sabale, P. M., Russo, F., Barluenga, S., & Winssinger, N. (2024) · JACS Au · doi:10.1021/jacsau.4c00738 · Cited by 1
Disrupting Protein–Protein Interfaces Using GRID Molecular Interaction Fields
Cross, S., Baroni, M., Ortuso, F., Alcaro, S., & Cruciani, G. (2013) · Springer eBooks · doi:10.1007/978-3-642-37999-4_3 · Cited by 1
Macrocyclic Organo‐Peptide Hybrids by Intein‐Mediated Ligation: Synthesis and Applications
Frost, J. R., & Fasan, R. (2017) · Wiley eBooks · doi:10.1002/9781119044116.ch11 · Cited by 1
The biophysical basis of protein domain compatibilityPreprint
Coyote‐Maestas, W., Nedrud, D., Suma, A., He, Y., Matreyek, K. A., Fowler, D. M., Carnevale, V., Myers, C. L., & Schmidt, D. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.09.418442 · Cited by 1
CNS Cancers
Graeme, R. (2010) · Wiley eBooks · doi:10.1002/0471266949.bmc223 · Cited by 1
Deep Alanine Scanning Reveals Potent Multi-alanine-substituted Protein–protein Interaction InhibitorsPreprint
Ye, X., Lee, Y., Gates, Z. P., Ling, Y., Mortensen, J., Yang, F.-S., Lin, Y., & Pentelute, B. L. (2021) · ChemRxiv · doi:10.26434/chemrxiv.13609499 · Cited by 1
Protein–Protein Interactions as Drug Discovery Targets
Dömling, A. S. S. (2010) · Wiley eBooks · doi:10.1002/0471266949.bmc129
Expression levels of MDM2 and MDMX proteins and their associated effects on P53 in human liposarcomas
Touqan, N. (2014) · UPT. Syiah Kuala University Library (Syiah Kuala University)
Molecular mechanisms of growth suppression by pharmacologically activated p53
Hedström, E. (2009) · Figshare
Insight into Interaction Mechanism of the Inhibitor pDI6W with MDM2 Based on Molecular Dynamics
Chen, J., Liang, Z.-Q. L. Z.-Q., Zhang, Q., Liu, X.-Y., Wang, W., & Liu, J.-Q. L. J.-Q. (2013) · The Journal of Atomic and Molecular Sciences · doi:10.4208/jmas.063012.072912a
Molecular Dynamics Insight into the Interaction Mechanism of Inhibitor PMI with MDMX
程, 伟. (2012) · Hans Journal of Computational Biology · doi:10.12677/hjcb.2012.23003
Development of a Mirror-Image Screening System for Chiral Natural Products
Noguchi, T. (2017) · Springer theses · doi:10.1007/978-981-10-6623-8_2
Macrocycles for Protein–Protein Interactions
Leitch, E. K., & Tavassoli, A. (2017) · doi:10.1002/9781119092599.ch8
Structure-guided disruption of pseudopilus tip inhibits Type II secretion in Pseudomonas aeruginosaPreprint
Jia, Z., Zhang, Y., Faucher, F., Zhang, W., Wang, S., Neville, N., Poole, K., & Zheng, J. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/303123
Cyclic Peptides as Chemical Probes
Serrano, L., Roper, G., & Kawamura, A. (2020) · Royal Society of Chemistry eBooks · doi:10.1039/9781839160745-00100
Helix-mimetics as Protein–Protein Interaction Inhibitors
Naiya, G., Chakraborty, M., Ghosh, P., & Roy, S. (2020) · Royal Society of Chemistry eBooks · doi:10.1039/9781788016544-00147
Yin Yang 1 regulation of tumor cell resistance to chemotherapeutic drugs
López-Pérez, T. V., Tirado-Rodríguez, B., Morales-Martínez, M., Montecillo-Aguado, M. R., & Huerta‐Yépez, S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821909-6.00016-x
Hitting "Undruggable" Targets: Determining the Properties of Cell Penetrant Stabilized Peptide Therapeutics for Intracellular Targets
Atangcho, L. (2020) · Deep Blue (University of Michigan)
The Role of the Mdm2/MdmX E3 Ligase System in Carcinogenesis, and Current Chemotherapeutic Interventions: A Literature Review
Ives, R., & Gandhi, K. (2021) · Undergraduate Research in Natural and Clinical Science and Technology (URNCST) Journal · doi:10.26685/urncst.262
A Novel Intramolecular Interaction in P53
He, F. (2020) · Digital Commons - University of South Florida (University of South Florida)
Vigor Kekuatan Tumbuh terhadap Fusarium sp. Pada Benih Kedelai (Glycine max. (L) Merrill)
Erawati (1989)
Applications of Constrained Helices
Li, Z., Zhao, H., & Wan, C. (2021) · Wiley eBooks · doi:10.1002/9783527343430.ch4
Protein-Protein Interaction Monitoring and Inhibitors Potency Evaluation Based on Crispr-Cas12a Sensing PlatformPreprint
Zhu, M., Pan, J., Xu, M., Cao, J., Zhu, Y., Zhu, H., Su, G., & Yu, Y. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4003254
A growth-based platform for detecting domain–peptide interactions in the cytoplasm of mammalian cells
Kimura, Y., Kashima, D., & Kawahara, M. (2022) · Scientific Reports · doi:10.1038/s41598-022-22770-4
Stapled peptides for new drug discovery
Liu, C., Wang, N., Chen, B., & Hu, H. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18611-0.00003-6
The solution structure of macrocyclic glecaprevir and its conformational adaptation mechanism towards antitumor targets
Wang, Q., Zhang, X., Xu, H., Jiang, Z., Jin, Y., Fang, W., & Wang, Z. (2024) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2024.139814
The Significant Role of Peptide Synthesis in the Early Days of Antimicrobial Peptide Research
Andreu, D. (2025) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-024-10678-8
Selection of MDM2-binding peptides in Escherichia coli using an engineered split intein and aminoglycoside phosphotransferase
Watanabe, Y., Tezuka, C., Nobusawa, K., & Takahashi, T. (2025) · Chemical Communications · doi:10.1039/d4cc06138a
Reengineering of a Proteomimetic Pan‐Ras Inhibitor into a Ras Degrader
Ongkingco, J. F., Hong, S. H., Toth, E. D., Nguyễn, T. T., & Arora, P. S. (2025) · Angewandte Chemie · doi:10.1002/ange.202507092
Cyclic Peptides for PPI Drug Discovery
Hu, H., & Li, X. (2025) · doi:10.1002/9783527845828.ch11
Conformational Heterogeneity of Pro–Pro Containing 23-Membered Ring Conopeptides by NMR
Dhurjad, P., Dannarm, S. R., Shaik, K., Wanjari, P., & Sonti, R. (2025) · ACS Omega · doi:10.1021/acsomega.5c05404
The role of NEDD8 pathway in cell invasion and strategies for the use of NEDD8 inhibitors in the clinic
Malhab, L. J. B. (2016) · theses.fr (ABES) · doi:10.70675/a9a79207z0857z4ed5zb207z749cdceb9430
Foldamères stabilisateurs d’hélices peptidiques : Applications à l’inhibition d’interactions protéine-protéine.
Mauran, L. (2017) · theses.fr (ABES) · doi:10.70675/98da08c1z91dbz4512za73dz22bf34b81ba6
Stabilisation et mimes de structures secondaires peptidiques : applications aux hélices alpha et feuillets beta
Perdriau, C. (2019) · theses.fr (ABES) · doi:10.70675/2e7e187bz8675z4e07zb97cz5cdd9e451dfd
SPAFESTWDILK, a plant-derived dodecapeptide from Zingiber officinale , as a predicted inhibitor of the MDM2–p53 interaction: computational discovery and multi-method evaluationPreprint
Massimiliano, R., Sandri, C., Paiola, G., & Ashtiani, M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.06.730565
Opto-MDMi: a dual-lock optogenetic system for robust activation of endogenous p53Preprint
Tsuruoka, T., Sumikama, T., Nakashima, S., Goto, Y., & Aoki, K. (2026) · eLife · doi:10.7554/elife.112082
Opto-MDMi: a dual-lock optogenetic system for robust activation of endogenous p53Preprint
Tsuruoka, T., Sumikama, T., Nakashima, S., Goto, Y., & Aoki, K. (2026) · eLife · doi:10.7554/elife.112082.1
BRCA1-derived peptide constructs exhibit sequence-dependent features compatible with modulation of the p53–MDM2 axis
Pektaş, S. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-12535-x
Protein–protein interaction inhibitors in the human proteome: lessons from 117 targeted interactions
Hyde, E., & Beekman, A. M. (2026) · RSC Medicinal Chemistry · doi:10.1039/d6md00552g
A Self-Assembled Affibody-Drug Conjugate Nanoagent for EGFR-Targeted Synergistic Codelivery of Exatecan and an MDM2 Inhibitory Peptide
Zhao, M., Gao, W., Xia, X., Xia, X., & Qian, Z. (2026) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.6c00580
Peptide-protein interactions in drug discovery
Ying, H., Lei, Y., Luo, Y., Zeng, J., & de la Fuente‐Núñez, C. (2026) · Cell Biomaterials · doi:10.1016/j.celbio.2026.100598
Organoid-Guided Synthetic Micropeptide Therapeutics to Target Ovarian Cancer Stem Cells
Balayoganandh, B., Gamit, N., Kallepalli, H., Dev, B., Dharmarajan, A., & Warrier, S. R. (2026) · Cancers · doi:10.3390/cancers18203289
BindingDB Entry 50012111: hDM2 protein-binding peptides screened from stapled α-helical peptide phage display libraries with different types of staple linkers.
BindingDB (2022) · UC San Diego · doi:10.7270/q2c82dz2
BindingDB Entry 50008481: Enhancing the Cell Permeability of Stapled Peptides with a Cyclic Cell-Penetrating Peptide.
BindingDB (2021) · UC San Diego · doi:10.7270/q2r49v5t
BindingDB Entry 50000844: d-Amino acid mutation of PMI as potent dual peptide inhibitors of p53-MDM2/MDMX interactions.
BindingDB (2020) · UC San Diego · doi:10.7270/q2dz0bsf
BindingDB Entry 3460: N-acylpolyamine inhibitors of HDM2 and HDMX binding to p53.
BindingDB (2009) · UC San Diego · doi:10.7270/q2057d90
BindingDB Entry 50044630: Rational improvement of the affinity and selectivity of integrin binding of grafted lasso peptides.
BindingDB (2015) · UC San Diego · doi:10.7270/q29w0h3x
BindingDB Entry 50001421: Artificial Macrocycles as Potent p53-MDM2 Inhibitors.
BindingDB (2020) · UC San Diego · doi:10.7270/q2tq6424
BindingDB Entry 50021995: Cellular, Structural Basis, and Recent Progress for Targeting Murine Double Minute X (MDMX) in Tumors.
BindingDB (2025) · UC San Diego · doi:10.7270/q2tf032p
BindingDB Entry 50032328: Functional profiling of p53-binding sites in Hdm2 and Hdmx using a genetic selection system.
BindingDB (2011) · UC San Diego · doi:10.7270/q2gm87j8
BindingDB Entry 50019884: Discovery of Sulanemadlin (ALRN-6924), the First Cell-Permeating, Stabilized α-Helical Peptide in Clinical Development.
BindingDB (2024) · UC San Diego · doi:10.7270/q2xd163b
BindingDB Entry 50012148: Rational Design of Right-Handed Heterogeneous Peptidomimetics as Inhibitors of Protein-Protein Interactions.
BindingDB (2022) · UC San Diego · doi:10.7270/q24m986g
BindingDB Entry 50040300: An ultrahigh affinity d-peptide antagonist Of MDM2.
BindingDB (2013) · UC San Diego · doi:10.7270/q20p1143

Authors: Pazgier, M., Liu, M., Zou, G., Yuan, W., Li, C., Li, C., Li, J., Monbo, J., Zella, D., Tarasov, S. G., & Lu, W.
Affiliations: University of Maryland, Baltimore (US)
National Cancer Institute (US)
ORCID: Pazgier, Marzena
Liu, Min
Zou, Guozhang
Li, Changqing
Li, Chong
Li, Jing
Zella, Davide
Tarasov, Sergey G.
Lu, Wuyuan
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2009-03-24
Volume: 106
Issue: 12
Pages: 4665-4670
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0900947106
PMC: PMC2660734
OpenAlex: W2076060796
Cited by: 391
References: 53
Citations by year: 2026: 10 · 2025: 28 · 2024: 27 · 2023: 23 · 2022: 18 · 2021: 29 · 2020: 25 · 2019: 24 · 2018: 18 · 2017: 31 · 2016: 18 · 2015: 20 · 2014: 24 · 2013: 21 · 2012: 19
FWCI: 12.67
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (AI056264)
National Institute of Allergy and Infectious Diseases (AI 061482, AI 056264, R21AI056264, R01AI061482)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
Keywords: p53, MDM2, MDMX, peptide inhibitors, transactivation domain, crystal structure, hydrogen bond network, hydrophobic cleft, p53 activators, anticancer drug design, phage display peptide library, native chemical ligation
MeSH terms: Amino Acid Sequence, Humans, Models, Molecular, Molecular Sequence Data, Nuclear Proteins, Oligopeptides, Peptides, Protein Binding, Proto-Oncogene Proteins, Structure-Activity Relationship, Tumor Suppressor Protein p53, Protein Structure, Secondary, Cell Cycle Proteins, Peptide Library, Proto-Oncogene Proteins c-mdm2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks