Structure–Activity Studies in a Family of β‐Hairpin Protein Epitope Mimetic Inhibitors of the p53–HDM2 Protein–Protein Interaction
Open accessAbstract
Inhibitors of the interaction between the p53 tumor‐suppressor protein and its natural human inhibitor HDM2 are attractive as potential anticancer agents. In earlier work we explored designing β‐hairpin peptidomimetics of the α‐helical epitope on p53 that would bind tightly to the p53‐binding site on HDM2. The β‐hairpin is used as a scaffold to display energetically hot residues in an optimal array for interaction with HDM2. The initial lead β‐hairpin mimetic, with a weak inhibitory activity (IC 50=125 μM), was optimized to afford cyclo‐(L‐Pro‐Phe‐Glu‐6ClTrp‐Leu‐Asp‐Trp‐Glu‐Phe‐D‐Pro) (where 6ClTrp=L‐6‐chlorotryptophan), which has an affinity almost 1000 times higher (IC 50=140 n M). In this work, insights into the origins of this affinity maturation based on structure–activity studies and an X‐ray crystal structure of the inhibitor/HDM2(residues 17–125) complex at 1.4 Å resolution are described. The crystal structure confirms the β‐hairpin conformation of the bound ligand, and also reveals that a significant component of the affinity increase arises through new aromatic/aromatic stacking interactions between side chains around the hairpin and groups on the surface of HDM2.
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
Cites
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
MOLMOL: A program for display and analysis of macromolecular structures
Koradi, R., Billeter, M., & Kurt Wüthrich, A. (1996) · Journal of Molecular Graphics · doi:10.1016/0263-7855(96)00009-4 · Cited by 7,163 · see citing works
Nicholls, A. O., Sharp, K. A., & Honig, B. H. (1991) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340110407 · Cited by 5,253 · see citing works
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 · see citing works
Interactions with Aromatic Rings in Chemical and Biological Recognition
Meyer, E. A., Castellano, R. K., & Diederich, F. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200390319 · Cited by 3,554 · see citing works
Torsion angle dynamics for NMR structure calculation with the new program Dyana
Güntert, P., Mumenthaler, C., & Kurt Wüthrich, A. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1284 · Cited by 2,781 · see citing works
Cation-π Interactions in Chemistry and Biology: A New View of Benzene, Phe, Tyr, and Trp
Dougherty, D. A. (1996) · Science · doi:10.1126/science.271.5246.163 · Cited by 2,658 · see citing works
Aromatic-Aromatic Interaction: A Mechanism of Protein Structure Stabilization
Burley, S. K., & Petsko, G. A. (1985) · Science · doi:10.1126/science.3892686 · Cited by 2,547 · see citing works
[16] SHELXL: High-resolution refinement
Sheldrick, G. M., & Schneider, T. R. (1997) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(97)77018-6 · Cited by 2,488 · see citing works
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 · see citing works
Anatomy of hot spots in protein interfaces
Bogan, A. A., & Thorn, K. S. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.1843 · Cited by 1,988 · see citing works
A Hot Spot of Binding Energy in a Hormone-Receptor Interface
Clackson, T., & Wells, J. A. (1995) · Science · doi:10.1126/science.7529940 · Cited by 1,987 · see citing works
The atomic structure of protein-protein recognition sites 1 1Edited by A. R. Fersht
Conte, L. L., Chothia, C., & Janin, J. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2439 · Cited by 1,967 · see citing works
An extensively modified version of MolScript that includes greatly enhanced coloring capabilities
Esnouf, R. M. (1997) · Journal of Molecular Graphics and Modelling · doi:10.1016/s1093-3263(97)00021-1 · Cited by 1,710 · see citing works
The program XEASY for computer-supported NMR spectral analysis of biological macromolecules
Bartels, C., Xia, T.-H., Billeter, M., Güntert, P., & Kurt Wüthrich, A. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00417486 · Cited by 1,636 · see citing works
Evaluation of single-crystal X-ray diffraction data from a position-sensitive detector
Kabsch, W. (1988) · Journal of Applied Crystallography · doi:10.1107/s0021889888007903 · Cited by 1,509 · see citing works
Shape Complementarity at Protein/Protein Interfaces
Lawrence, M. C., & Colman, P. M. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1648 · Cited by 1,219 · see citing works
Shape complementarity at protein–protein interfaces
Norel, R., Lin, S. L., Wolfson, H. J., & Nussinov, R. (1994) · Biopolymers · doi:10.1002/bip.360340711 · Cited by 1,208 · see citing works
NMR Spectroscopy Techniques for Screening and Identifying Ligand Binding to Protein Receptors
Meyer, B., & Peters, T. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200390233 · Cited by 1,042 · see citing works
Efficient anisotropic refinement of macromolecular structures using FFT
Murshudov, G. N., Vagin, A. A., Lebedev, A., Wilson, K. S., & Dodson, E. J. (1999) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s090744499801405x · Cited by 937 · see citing works
Amino‐aromatic interactions in proteins
Burley, S. K., & Petsko, G. A. (1986) · FEBS Letters · doi:10.1016/0014-5793(86)80730-x · Cited by 769 · see citing works
Inhibiting the p53–MDM2 interaction: an important target for cancer therapy
Chène, P. (2003) · Nature Reviews Cancer · doi:10.1038/nrc991 · Cited by 765 · see citing works
Hunter, C. A., Singh, J., & Thornton, J. M. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)90271-7 · Cited by 644 · see citing works
Beyond Watson and Crick: DNA Methylation and Molecular Enzymology of DNA Methyltransferases
Jeltsch, A. (2002) · ChemBioChem · doi:10.1002/1439-7633(20020402)3:4 · Cited by 614 · see citing works
Self-citationWechselwirkungen mit aromatischen Ringen in chemischen und biologischen Erkennungsprozessen
Meyer, E. A., Castellano, R. K., & Diederich, F. (2003) · Angewandte Chemie · doi:10.1002/ange.200390290 · Cited by 552 · see citing works
Binding in the growth hormone receptor complex.
Wells, J. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.1.1 · Cited by 439 · see citing works
Discovery and Cocrystal Structure of Benzodiazepinedione HDM2 Antagonists That Activate p53 in Cells
Grasberger, B. L., Lu, T., Schubert, C., Parks, D. J., Carver, T. E., Koblish, H. K., Cummings, M. D., LaFrance, L. V., Milkiewicz, K. L., Calvo, R. R., et al. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm049137g · Cited by 433 · see citing works
Design of a synthetic Mdm2-binding mini protein that activates the p53 response in vivo
Böttger, A., Böttger, V., Sparks, A., Liu, W.-L., Howard, S. F., & Lane, D. P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00374-5 · Cited by 363 · see citing works
Molecular Mechanism of the Interaction between MDM2 and p53
Schön, O., Friedler, A., Bycroft, M., Freund, S. M. V., & Fersht, A. R. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00852-5 · Cited by 349 · see citing works
Minimal model systems for β-sheet secondary structure in proteins
Gellman, S. H. (1998) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(98)80109-9 · Cited by 332 · see citing works
Helical β-Peptide Inhibitors of the p53-hDM2 Interaction
Kritzer, J. A., Lear, J. D., Hodsdon, M. E., & Schepartz, A. (2004) · Journal of the American Chemical Society · doi:10.1021/ja031625a · Cited by 314 · see citing works
Inhibition of Protein−Protein Association by Small Molecules: Approaches and Progress
Toogood, P. L. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm010468s · Cited by 281 · see citing works
Clackson, T., Ultsch, M. H., Wells, J. A., & de Vos, A. M. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.1669 · Cited by 278 · see citing works
Chalcone Derivatives Antagonize Interactions between the Human Oncoprotein MDM2 and p53
Stoll, R., Renner, C., Hansen, S., Palme, S., Klein, C., Belling, A., Żesławski, W., Kamionka, M., Rehm, T., Mühlhahn, P., et al. (2000) · Biochemistry · doi:10.1021/bi000930v · Cited by 275 · see citing works
Halogenation of Drugs Enhances Membrane Binding and Permeation
Gerebtzoff, G., Li‐Blatter, X., Fischer, H., Frentzel, A., & Seelig, A. (2004) · ChemBioChem · doi:10.1002/cbic.200400017 · Cited by 273 · see citing works
Terphenyl‐Based Helical Mimetics That Disrupt the p53/HDM2 Interaction
Yin, H. H., Lee, G., Park, H. S., Payne, G. A., Rodriguez, J. M., Sebti, S. M., & Hamilton, A. D. (2005) · Angewandte Chemie International Edition · doi:10.1002/anie.200462316 · Cited by 254 · see citing works
Garcı́a-Echeverrı́a, C., Chêne, P., Blommers, M. J. J., & Furet, P. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm990966p · Cited by 246 · see citing works
The modular architecture of protein–protein binding interfaces
Reichmann, D., Rahat, O., Albeck, S., Meged, R., Dym, O., & Schreiber, G. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407280102 · Cited by 239 · see citing works
NMR-based screening in drug discovery
Hajduk, P. J., Meadows, R. P., & Fesik, S. W. (1999) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583500003528 · Cited by 229 · see citing works
Fasan, R., Dias, R. L. A., Moehle, K., Zerbe, O., Vrijbloed, J. W., Obrecht, D., & Robinson, J. A. (2004) · Angewandte Chemie International Edition · doi:10.1002/anie.200353242 · Cited by 183 · see citing works
Self-citationIdentification of novel mdm2 binding peptides by phage display.
Böttger, V., Böttger, A., Howard, S. F., Picksley, S. M., Chêne, P., Garcı́a-Echeverrı́a, C., Hochkeppel, H. K., & Lane, D. P. (1996) · PubMed · Cited by 182 · see citing works
Biosynthesis of Proteins Incorporating a Versatile Set of Phenylalanine Analogues
Kirshenbaum, K., Carrico, I. S., & Tirrell, D. A. (2002) · ChemBioChem · doi:10.1002/1439-7633(20020301)3:2/3 · Cited by 172 · see citing works
Isolation and Structure Elucidation of Chlorofusin, a Novel p53-MDM2 Antagonist from a Fusarium sp.
Duncan, S. J., Grüschow, S., Williams, D. H., McNicholas, C., Purewal, R., Hájek, M., Gerlitz, M., Martin, S., Wrigley, S. K., & Moore, M. (2001) · Journal of the American Chemical Society · doi:10.1021/ja002940p · Cited by 171 · see citing works
Parks, D. J., LaFrance, L. V., Calvo, R. R., Milkiewicz, K. L., Gupta, V., Lattanze, J., Ramachandren, K., Carver, T. E., Petrella, E. C., Cummings, M. D., et al. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2004.11.009 · Cited by 170 · see citing works
NMR‐Techniken zum Screening und zur Identifizierung der Bindung von Liganden an Proteinrezeptoren
Meyer, B., & Peters, T. (2003) · Angewandte Chemie · doi:10.1002/ange.200390202 · Cited by 150 · see citing works
In Vivo Photocrosslinking with Unnatural Amino Acid Mutagenesis
Chin, J. W., & Schultz, P. G. (2002) · ChemBioChem · doi:10.1002/1439-7633(20021104)3:11 · Cited by 149 · see citing works
Self-citationUhrı́nová, S., Uhrı́n, D., Powers, H., Watt, K., Zheleva, D. I., Fischer, P. M., McInnes, C., & Barlow, P. N. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.05.010 · Cited by 141 · see citing works
Chêne, P., Fuchs, J. P., Bohn, J. A., Garcı́a-Echeverrı́a, C., Furet, P., & Fabbro, D. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3738 · Cited by 139 · see citing works
Maignan, S., Guilloteau, J. P., Choi-Sledeski, Y. M., Becker, M. R., Ewing, W. R., Pauls, H. W., Spada, A. P., & Mikol, V. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm0203837 · Cited by 123 · see citing works
Design of β-sheet systems for understanding the thermodynamics and kinetics of protein folding
Searle, M. S., & Ciani, B. (2004) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2004.06.001 · Cited by 116 · see citing works
Takeuchi, Y., & Marshall, G. R. (1998) · Journal of the American Chemical Society · doi:10.1021/ja970855k · Cited by 114 · see citing works
Favre, M., Moehle, K., Jiang, L., Pfeiffer, B., & Robinson, J. A. (1999) · Journal of the American Chemical Society · doi:10.1021/ja984016p · Cited by 113 · see citing works
Self-citationTucker, T. J., Brady, S. F., Lumma, W. C., Lewis, S. D., Gardell, S. J., Naylor-Olsen, A. M., Yan, Y., Sisko, J. T., Stauffer, K. J., Lucas, B. J., et al. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm9801713 · Cited by 106 · see citing works
p53 α-Helix mimetics antagonize p53/MDM2 interaction and activate p53
Chen, L., Yin, H. H., Farooqi, B., Sebti, S. M., Hamilton, A. D., & Chen, J. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-04-0342 · Cited by 97 · see citing works
Athanassiou, Z., Dias, R. L. A., Moehle, K., Dobson, N., Varani, G., & Robinson, J. A. (2004) · Journal of the American Chemical Society · doi:10.1021/ja0497680 · Cited by 96 · see citing works
Self-citationFlexible lid to the p53-binding domain of human Mdm2: Implications for p53 regulation
McCoy, M. A., Gesell, J. J., Senior, M. M., & Wyss, D. F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0334477100 · Cited by 95 · see citing works
Isoindolinone-based inhibitors of the MDM2–p53 protein–protein interaction
Hardcastle, I. R., Ahmed, S. U., Atkins, H., Calvert, H., Curtin, N. J., Farnie, G., Golding, B. T., Griffin, R. J., Guyenne, S., Hutton, C., et al. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2004.12.061 · Cited by 93 · see citing works
Crystal Structures of Two Potent Nonamidine Inhibitors Bound to Factor Xa ,
Adler, M., Kochanny, M. J., Ye, B., Rumennik, G., Light, D. R., Biancalana, S., & Whitlow, M. D. (2002) · Biochemistry · doi:10.1021/bi0264061 · Cited by 93 · see citing works
Galatin, P. S., & Abraham, D. J. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm034182u · Cited by 90 · see citing works
Kanovsky, M., Raffo, A. J., Drew, L., Rosal, R. V., Do, T., Friedman, F. K., Rubinstein, P., Visser, J. W. M., Robinson, R., Brandt‐Rauf, P. W., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211280698 · Cited by 90 · see citing works
Aib‐based peptide backbone as scaffolds for helical peptide mimics
Banerjee, R., Basu, G., Roy, S., & Chêne, P. (2002) · Journal of Peptide Research · doi:10.1034/j.1399-3011.2002.201005.x · Cited by 84 · see citing works
Sibanda, B. L., & Thornton, J. M. (1991) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(91)02007-v · Cited by 82 · see citing works
Robinson, J. A., Shankaramma, S. C., Jetter, P., Kienzl, U., Schwendener, R. A., Vrijbloed, J. W., & Obrecht, D. (2005) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2005.01.009 · Cited by 80 · see citing works
Self-citationNMR Spectroscopy Tools for Structure‐Aided Drug Design
Homans, S. W. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200300581 · Cited by 80 · see citing works
Peptide models of protein β-sheets: design, folding and insights into stabilising weak interactions
Searle, M. S. (2001) · Journal of the Chemical Society Perkin Transactions 2 · doi:10.1039/b008074h · Cited by 77 · see citing works
Solution Structure of a β-Peptide Ligand for hDM2
Kritzer, J. A., Hodsdon, M. E., & Schepartz, A. (2005) · Journal of the American Chemical Society · doi:10.1021/ja042933r · Cited by 73 · see citing works
Haginoya, N., Kobayashi, S., Komoriya, S., Yoshino, T., Suzuki, M., Shimada, T., Watanabe, K., Hirokawa, Y., Furugori, T., & Nagahara, T. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049884d · Cited by 72 · see citing works
Terphenyl‐Based Helical Mimetics That Disrupt the p53/HDM2 Interaction
Yin, H. H., Lee, G., Park, H. S., Payne, G. A., Rodriguez, J. M., Sebti, S. M., & Hamilton, A. D. (2005) · Angewandte Chemie · doi:10.1002/ange.200462316 · Cited by 67 · see citing works
Thermodynamics of p53 Binding to hdm2(1–126): Effects of Phosphorylation and p53 Peptide Length
Lai, Z., Auger, K. R., Manubay, C. M., & Copeland, R. A. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2000.1998 · Cited by 64 · see citing works
Experimental Measurement of Noncovalent Interactions Between Halogens and Aromatic Rings
Adams, H., Cockroft, S. L., Guardigli, C., Hunter, C. A., Lawson, K. R., Perkins, J., Spey, S. E., Urch, C. J., & Ford, R. (2004) · ChemBioChem · doi:10.1002/cbic.200400018 · Cited by 60 · see citing works
Binding of p53-derived Ligands to MDM2 Induces a Variety of Long Range Conformational Changes
Schön, O., Friedler, A., Freund, S. M. V., & Fersht, A. R. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.11.051 · Cited by 58 · see citing works
Transformation of Low-Affinity Lead Compounds into High-Affinity Protein Capture Agents
Reddy, M. M., Bachhawat‐Sikder, K., & Kodadek, T. J. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.05.013 · Cited by 57 · see citing works
Binding of an inhibitor of the p53/MDM2 Interaction to MDM2
Duncan, S. J., Cooper, M. A., & Williams, D. H. (2003) · Chemical Communications · doi:10.1039/b211889k · Cited by 56 · see citing works
Fasan, R., Dias, R. L. A., Moehle, K., Zerbe, O., Vrijbloed, J. W., Obrecht, D., & Robinson, J. A. (2004) · Angewandte Chemie · doi:10.1002/ange.200353242 · Cited by 48 · see citing works
Self-citationSpäth, J., Stuart, F., Jiang, L., & Robinson, J. A. (1998) · Helvetica Chimica Acta · doi:10.1002/(sici)1522-2675(19980909)81:9 · Cited by 41 · see citing works
Self-citationPeptoid residues and β‐turn formation
Rainaldi, M., Moretto, V., Crisma, M., Peggion, E., Mammi, S., Toniolo, C., & Cavicchioni, G. (2002) · Journal of Peptide Science · doi:10.1002/psc.392 · Cited by 39 · see citing works
A family of macrocyclic antibiotics with a mixed peptide–peptoid ß-hairpin backbone conformation
Shankaramma, S. C., Moehle, K., James, S. P., Vrijbloed, J. W., Obrecht, D., & Robinson, J. A. (2003) · Chemical Communications · doi:10.1039/b304310j · Cited by 37 · see citing works
Self-citationKnight, S. M. G., Umezawa, N., Lee, H., Gellman, S. H., & Kay, B. K. (2002) · Analytical Biochemistry · doi:10.1006/abio.2001.5468 · Cited by 35 · see citing works
On the Use of Strong Patterson Function Signals in Many-Body Molecular Replacement
Navaza, J., Panepucci, E., & Martin, C. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444997019434 · Cited by 19 · see citing works
Garcı́a-Echeverrı́a, C., Furet, P., & Chêne, P. (2001) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(01)00394-8 · Cited by 15 · see citing works
Stoll, R., Renner, C., Mühlhahn, P., Hansen, S., Schumacher, R., Hesse, F., Kaluza, B., Engh, R. A., Voelter, W., & Holak, T. A. (2000) · Journal of Biomolecular NMR · doi:10.1023/a:1008365622798 · Cited by 15 · see citing works
Frank, O., & Hofmann, T. F. (2000) · Helvetica Chimica Acta · doi:10.1002/1522-2675(20001220)83:12 · Cited by 11 · see citing works
(1-Benzimidazolonyl)alanine (Bia): preliminary investigations into a potential tryptophan mimetic
Huber, V. J., Arroll, T. W., Lum, C., Goodman, B. A., & Nakanishi, H. (2002) · Tetrahedron Letters · doi:10.1016/s0040-4039(02)01501-0 · Cited by 11 · see citing works
NMR‐Methoden zum strukturgestützten Wirkstoff‐Design
Homans, S. W. (2003) · Angewandte Chemie · doi:10.1002/ange.200300581 · Cited by 6 · see citing works
Flagged first, then by citations
1 of the 84 references couldn’t be matched to a known paper.
Research works printed but not linked: 75
- D. Reichmann, O. Rahat, S. Albeck, R. Meged, O. Dym, G. Schreiber, Proc. Natl. Acad. Sci. USA 2005, 102, 57.
- A. A. Bogan, K. S. Thorn, J. Mol. Biol. 1998, 280, 1.
- T. Clackson, J. A. Wells, Science 1995, 267, 383.
- T. Clackson, M. H. Ultsch, J. A. Wells, A. M. de Vos, J. Mol. Biol. 1998, 277, 1111.
- L. Lo Conte, C. Chothia, J. Janin, J. Mol. Biol. 1999, 285, 2177.
- P. L. Toogood, J. Med. Chem. 2002, 45, 1543.
- J. A. Wells, Proc. Natl. Acad. Sci. USA 1996, 93, 1.
- J. Späth, F. Stuart, L. Jiang, J. A. Robinson, Helv. Chim. Acta 1998, 81, 1726.
- L. Jiang, K. Moehle, B. Dhanapal, D. Obrecht, J. A. Robinson, Helv. Chim. Acta 2000, 83, 3097.
- M. Favre, K. Moehle, L. Jiang, B. Pfeiffer, J. A. Robinson, J. Am. Chem. Soc. 1999, 121, 2679.
- A. Descours, K. Moehle, A. Renard, J. A. Robinson, ChemBioChem 2002, 3, 318.
- J. A. Robinson, S. C. Shankaramma, P. Jetter, U. Kienzl, R. A. Schwenden- er, J. W. Vrijbloed, D. Obrecht, Bioorg. Med. Chem. 2005, 13, 2055.
- S. C. Shankaramma, Z. Athanassiou, O. Zerbe, K. Moehle, C. Mouton, F. Bernardini, J. W. Vrijbloed, D. Obrecht, J. A. Robinson, ChemBioChem 2002, 3, 1126.
- Z. Athanassiou, R. L. A. Dias, K. Moehle, N. Dobson, G. Varani, J. A. Robinson, J. Am. Chem. Soc. 2004, 126, 6906.
- R. Fasan, R. L. A. Dias, K. Moehle, O. Zerbe, J. W. Vrijbloed, D. Obrecht, J. A. Robinson, Angew. Chem. 2004, 116, 2161; Angew. Chem. Int. Ed. 2004, 43, 2109.
- P. ChØne, Nat. Rev. Cancer 2003, 3, 102.
- P. H. Kussie, S. Gorina, V. Marechal, B. Elenbaas, J. Moreau, A. J. Levine, N. P. Pavletich, Science 1996, 274, 948.
- O. Schon, A. Friedler, M. Bycroft, S. M. Freund, A. R. Fersht, J. Mol. Biol. 2002, 323, 491.
- Z. Lai, K. R. Auger, C. M. Manubay, R. A. Copeland, Arch. Biochem. Bio- phys. 2000, 381, 278.
- B. L. Sibanda, J. M. Thornton, Methods Enzymol. 1991, 202, 59.
- B. Meyer, T. Peters, Angew. Chem. 2003, 115, 890; Angew. Chem. Int. Ed. 2003, 42, 864.
- S. W. Homans, Angew. Chem. 2004, 116, 292; Angew. Chem. Int. Ed. 2004, 43, 290.
- P. J. Hajduk, R. P. Meadows, S. W. Fesik, Quart. Rev. Biophys. 1999, 32, 211.
- R. Stoll, C. Renner, P. Mühlhahn, S. Hansen, R. Schumacher, F. Hesse, B. Kaluza, R. A. Engh, W. Voelter, T. A. Holak, J. Biomol. NMR 2000, 17, 91.
- O. Schon, A. Friedler, S. Freund, A. R. Fersht, J. Mol. Biol. 2004, 336, 197.
- S. H. Gellman, Curr. Opin. Chem. Biol. 1998, 2, 717.
- M. S. Searle, J. Chem. Soc. Perkin Trans. 2 2001, 1011.
- M. S. Searle, B. Ciani, Curr. Opin. Struct. Biol. 2004, 14, 458.
- M. Rainaldi, V. Moretto, M. Crisma, E. Peggion, S. Mammi, C. Toniolo, G. Cavicchioni, J. Pept. Sci. 2002, 8, 241.
- Y. Takeuchi, G. R. Marshall, J. Am. Chem. Soc. 1998, 120, 5363.
- C. Garcia-Echeverria, P. ChØne, M. J. J. Blommers, P. Furet, J. Med. Chem. 2000, 43, 3205.
- M. C. Lawrence, P. M. Colman, J. Mol. Biol. 1993, 234, 946.
- L. T. Vassilev, B. T. Vu, B. Graves, D. Carvajal, F. Podlaski, Z. Filipovic, N. Kong, U. Kammlott, C. Lukacs, C. Klein, N. Fotouhi, E. A. Liu, Science 2004, 303, 844.
- S. Uhrinova, D. Uhrin, H. Powers, K. Watt, D. Zheleva, P. Fischer, C. McInnes, P. N. Barlow, J. Mol. Biol. 2005, 350, 587.
- S. K. Burley, G. A. Petsko, Science 1985, 229, 23.
- C. A. Hunter, J. Singh, J. M. Thornton, J. Mol. Biol. 1991, 218, 837.
- E. A. Meyer, R. K. Castellano, F. Diederich, Angew. Chem. 2003, 115, 1244; Angew. Chem. Int. Ed. 2003, 42, 1210.
- M. A. McCoy, J. J. Gesell, M. M. Senior, D. F. Wyss, Proc. Natl. Acad. Sci. USA 2003, 100, 1645.
- H. Adams, S. Cockroft, C. Guardigli, C. A. Hunter, K. R. Lawson, J. Perkins, S. E. Spey, C. J. Urch, R. Ford, ChemBioChem 2004, 5, 657.
- D. A. Dougherty, Science 1996, 271, 163.
- S. K. Burley, G. A. Petsko, FEBS Lett. 1986, 203, 139.
- M. T. Stubbs, S. Reyda, F. Dullweber, M. Müller, G. Klebe, D. Dorsch, W. W. K. R. Mederski, H. Wurziger, ChemBioChem 2002, 3, 246.
- S. Maignan, J.-P. Guilloteau, Y. M. Choi-Sledeski, M. R. Becker, W. R. Ewing, H. W. Pauls, A. P. Spada, V. Mikol, J. Med. Chem. 2003, 46, 685.
- N. Haginoya, S. Kobayashi, S. Komoriya, T. Yoshino, M. Suzuki, T. Shi- mada, K. Watanabe, Y. Hirokawa, T. Furugori, T. Nagahara, J. Med. Chem. 2004, 47, 5167.
- M. Adler, M. J. Kochanny, B. Ye, G. Rumennik, D. R. Light, S. Biancalana, M. Whitlow, Biochemistry 2002, 41, 15 514.
- T. J. Tucker, S. F. Brady, W. C. Lumma, S. D. Lewis, S. J. Gardel, A. M. Naylor-Olsen, Y. Yan, J. T. Sisko, K. J. Stauffer, B. Y. Lucas, J. J. Lynch, J. J. Cook, M. T. Stranieri, M. A. Holahan, E. A. Lyle, E. P. Baskin, I.-W. Chen, K. B. Dancheck, J. A. Krueger, C. M. Cooper, J. P. Vacca, J. Med. Chem. 1998, 41, 3210.
- G. Gerebtzoff, X. LiBlatter, H. Fischer, A. Frentzel, A. Seelig, ChemBio- Chem 2004, 5, 676.
- S. J. Duncan, S. Grüschow, D. H. Williams, C. McNicholas, R. Purewal, M. Hajek, M. Gerlitz, S. Martin, S. K. Wrigley, M. Moore, J. Am. Chem. Soc. 2001, 123, 554.
- V. J. Huber, T. W. Arroll, C. Lum, B. A. Goodman, H. Nakanishi, Tetrahe- dron Lett. 2002, 43, 6729.
- S. M. G. Knight, N. Umezawa, H.-S. Lee, S. H. Gellman, B. K. Kay, Anal. Bio- chem. 2002, 300, 230.
- M. Kanovsky, A. Raffo, L. Drew, R. Rosal, T. Do, F. K. Friedman, P. Rubin- stein, J. Visser, R. Robinson, P. W. Brandt-Rauf, J. Michl, R. L. Fine, M. R. Pincus, Proc. Natl. Acad. Sci. USA 2001, 98, 12 438.
- A. Bçttger, V. Bçttger, A. Sparks, W.-L. Liu, S. F. Howard, D. P. Lane, Cur- rent Biol. 1997, 7, 860.
- V. Bçttger, A. Bçttger, S. F. Howard, S. M. Picksley, P. ChØne, C. Garcia- Echeverria, H.-K. Hochkeppel, D. P. Lane, Oncogene 1996, 13, 2141.
- P. ChØne, J. Fuchs, J. Bohn, C. Garcia-Echeverria, P. Furet, D. Fabbro, J. Mol. Biol. 2000, 299, 245.
- C. Garcia-Echeverria, P. Furet, P. ChØne, Bioorg. Med. Chem. Lett. 2001, 11, 2161.
- R. Banerjee, G. Basu, P. ChØne, S. Roy, J. Pept. Res. 2002, 60, 88.
- B. L. Grasberger, T. B. Lu, C. Schubert, D. J. Parks, T. E. Carver, H. K. Kob- lish, M. D. Cummings, L. V. LaFrance, K. L. Milkiewicz, R. R. Calvo, D. Ma- guire, J. Lattanze, C. F. Franks, S. Y. Zhao, K. Ramachandren, G. R. Bylebyl, M. Zhang, C. L. Manthey, E. C. Petrella, M. W. Pantoliano, I. C. Deckman, J. C. Spurlino, A. C. Maroney, B. E. Tomczuk, C. J. Molloy, R. F. Bone, J. Med. Chem. 2005, 48, 909.
- J. A. Kritzer, J. D. Lear, M. E. Hodsdon, A. Schepartz, J. Am. Chem. Soc. 2004, 126, 9468.
- J. A. Kritzer, M. E. Hodsdon, A. Schepartz, J. Am. Chem. Soc. 2005, 127, 4118.
- M. M. Reddy, K. Bachhawat-Sikder, T. Kodadek, Chem. Biol. 2004, 11, 1127.
- R. Stoll, C. Renner, S. Hansen, S. Palme, C. Klein, A. Belling, W. Zeslawski, M. Kamionka, T. Rehm, P. Muhlhahn, R. Schumacher, F. Hesse, B. Kaluza, W. Voelter, R. A. Engh, T. A. Holak, Biochemistry 2001, 40, 336.
- I. R. Hardcastle, S. U. Ahmed, H. Atkins, A. H. Calvert, N. J. Curtin, G. Farnie, B. T. Golding, R. J. Griffin, S. Guyenne, C. Hutton, P. Kallbad, S. J. Kemp, M. S. Kitching, D. R. Newell, S. Norbedo, J. S. Northen, R. J. Reid, K. Saravanan, H. M. G. Willems, J. Lunec, Bioorg. Med. Chem. Lett. 2005, 15, 1515.
- D. J. Parks, L. V. LaFrance, R. R. Calvo, K. L. Milkiewicz, V. Gupta, J. Lat- tanze, K. Ramachandren, T. E. Carver, E. C. Petrella, M. D. Cummings, D. Maguire, B. L. Grasberger, T. B. Lu, Bioorg. Med. Chem. Lett. 2005, 15, 765.
- H. Yin, G. I. Lee, H. S. Park, G. A. Payne, J. M. Rodriguez, S. M. Sebti, A. D. Hamilton, Angew. Chem. 2005, 117, 2764; Angew. Chem. Int. Ed. 2005, 44, 2704.
- L. H. Chen, H. Yin, B. Farooqi, S. Sebti, A. D. Hamilton, J. D. Chen, Mol. Cancer Ther. 2005, 4, 1019.
- P. S. Galatin, D. J. Abraham, J. Med. Chem. 2004, 47, 4163.
- W. Kabsch, J. Appl. Crystallogr. 1988, 21, 916.
- J. Navaza, E. H. Panepucci, C. Martin, Acta Crystallogr. Sect. D Biol. Crys- tallogr. 1998, 54, 817.
- G. N. Murshudov, A. A. Vagin, A. Lebedev, K. S. Wilson, E. J. Dodson, Acta Crystallogr. Sect. D Biol. Crystallogr. 1999, 55, 247.
- G. M. Sheldrick, T. R. Schneider, Methods Enzymol. 1997, 277, 319.
- A. Nicholls, K. Sharp, B. Honig, Proteins 1991, 11, 281.
- R. Koradi, M. Billeter, K. Wüthrich, J. Mol. Graphics 1996, 14, 51.
- R. M. Esnouf, J. Mol. Graphics Modell. 1997, 15, 132.
- P. Güntert, C. Mumenthaler, K. Wüthrich, J. Mol. Biol. 1997, 273, 283.
- C. Bartels, T. Xia, M, Billeter, P. Guentert, K. Wüthrich, J. Biomol. NMR 1995, 6, 1. Received: November 2, 2005 526 www.chembiochem.org 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim ChemBioChem 2006, 7, 515 -526
Cited by
Sorted by citations
Aromatic Rings in Chemical and Biological Recognition: Energetics and Structures
Salonen, L. M., Ellermann, M., & Diederich, F. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201007560 · Cited by 1,542 · see citing works
Inhibition of α-helix-mediated protein–protein interactions using designed molecules
Azzarito, V., Long, K., Murphy, N. S., & Wilson, A. J. (2013) · Nature Chemistry · doi:10.1038/nchem.1568 · Cited by 727 · see citing works
Pelay‐Gimeno, M., Glas, A., Koch, O., & Grossmann, T. N. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201412070 · Cited by 718 · see citing works
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 · see citing works
Constraining Cyclic Peptides To Mimic Protein Structure Motifs
Hill, T. A., Shepherd, N. E., Diness, F., & Fairlie, D. P. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201401058 · Cited by 418 · see citing works
Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX
Pazgier, M., Liu, M., Zou, G., Yuan, W., Li, C., Li, C., Li, J., Monbo, J., Zella, D., Tarasov, S. G., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900947106 · Cited by 391 · see citing works
β-Hairpin Peptidomimetics: Design, Structures and Biological Activities
Robinson, J. A. (2008) · Accounts of Chemical Research · doi:10.1021/ar700259k · Cited by 321 · see citing works
Self-citationInhibition of protein–protein interactions using designed molecules
Wilson, A. J. (2009) · Chemical Society Reviews · doi:10.1039/b807197g · Cited by 262 · see citing works
Aromatische Ringe in chemischer und biologischer Erkennung: Energien und Strukturen
Salonen, L. M., Ellermann, M., & Diederich, F. (2011) · Angewandte Chemie · doi:10.1002/ange.201007560 · Cited by 254 · see citing works
Binding Site Detection and Druggability Index from First Principles
Seco, J., Luque, F. J., & Barril, X. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm801385d · Cited by 240 · see citing works
Targeting protein–protein interactions: Lessons from p53/MDM2
Murray, J. K., & Gellman, S. H. (2007) · Biopolymers · doi:10.1002/bip.20741 · Cited by 186 · see citing works
Cino, E. A., Choy, W., & Karttunen, M. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct300323g · Cited by 184 · see citing works
Peptide-based inhibitors of protein–protein interactions
Wójcik, P., & Berlicki, Ł. (2015) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2015.12.084 · Cited by 177 · see citing works
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 · see citing works
Shaginian, A., Whitby, L. R., Hong, S., Hwang, I., Farooqi, B., Searcey, M., Chen, J., Vogt, P. K., & Boger, D. L. (2009) · Journal of the American Chemical Society · doi:10.1021/ja810025g · Cited by 144 · see citing works
The design, structures and therapeutic potential of protein epitope mimetics
Robinson, J. A., DeMarco, S. T., Gombert, F. O., Moehle, K., & Obrecht, D. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2008.07.008 · Cited by 137 · see citing works
Self-citationMolecular Basis for the Inhibition of p53 by Mdmx
Popowicz, G. M., Czarna, A., Rothweiler, U., Szwagierczak, A., Krajewski, M., Weber, L., & Holak, T. A. (2007) · Cell Cycle · doi:10.4161/cc.6.19.4740 · Cited by 131 · see citing works
Small Molecule Inhibitors of the MDM2-p53 Interaction Discovered by Ensemble-Based Receptor Models
Bowman, A. L., Nikolovska‐Coleska, Z., Zhong, H. A., Wang, S., & Carlson, H. A. (2007) · Journal of the American Chemical Society · doi:10.1021/ja073687x · Cited by 127 · see citing works
Hogg, T., Nagarajan, K., Herzberg, S., Chen, L., Shen, X., Jiang, H., Wecke, M., Blohmke, C. J., Hilgenfeld, R., & Schmidt, C. L. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603776200 · Cited by 126 · see citing works
Targeting Protein–Protein Interactions and Fragment-Based Drug Discovery
Valkov, E., Sharpe, T., Marsh, M., Greive, S., & Hyvönen, M. (2011) · Topics in Current Chemistry · doi:10.1007/128_2011_265 · Cited by 107 · see citing works
Pelay‐Gimeno, M., Glas, A., Koch, O., & Grossmann, T. N. (2015) · Angewandte Chemie · doi:10.1002/ange.201412070 · Cited by 90 · see citing works
de Vega, M. J. P., Martín‐Martinez, M., & González‐Muñiz, R. (2006) · Current Topics in Medicinal Chemistry · doi:10.2174/156802607779318325 · Cited by 90 · see citing works
Ninković, D. B., Filipović, J. P. B., Hall, M. B., Brothers, E. N., & Zarić, S. D. (2020) · ACS Central Science · doi:10.1021/acscentsci.0c00005 · Cited by 87 · see citing works
Small-molecule inhibitors of MDM2 as new anticancer therapeutics
Dickens, M. P., Fitzgerald, R. P., & Fischer, P. M. (2009) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2009.10.003 · Cited by 86 · see citing works
Discovery and optimization of peptide macrocycles
White, A. M., & Craik, D. J. (2016) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2016.1245720 · Cited by 83 · see citing works
N-alkylated oligoamide α-helical proteomimetics
Campbell, F., Plante, J. P., Edwards, T. A., Warriner, S. L., & Wilson, A. J. (2010) · Organic & Biomolecular Chemistry · doi:10.1039/c001164a · Cited by 82 · see citing works
Folding of a Linear Array of α-Amino Acids within a Helical Aromatic Oligoamide Frame
Kudo, M., Maurizot, V., Kauffmann, B., Tanatani, A., & Huc, I. (2013) · Journal of the American Chemical Society · doi:10.1021/ja404656z · Cited by 81 · see citing works
An Ultrahigh Affinity d -Peptide Antagonist Of MDM2
Zhan, C., Zhao, L., Wei, X., Wu, X., Chen, X., Yuan, W., Lu, W., Pazgier, M., & Lu, W. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3005465 · Cited by 80 · see citing works
Peptidomimetics: A Synthetic Tool for Inhibiting Protein–Protein Interactions in Cancer
Mabonga, L., & Kappo, A. P. (2019) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-019-09831-5 · Cited by 78 · see citing works
Stable Peptides Instead of Stapled Peptides: Highly Potent αvβ6‐Selective Integrin Ligands
Maltsev, O. V., Marelli, U. K., Kapp, T. G., Leva, F. S. D., Maro, S. D., Nieberler, M., Reuning, U., Schwaiger, M., Novellino, E., Marinelli, L., et al. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201508709 · Cited by 78 · see citing works
Molecular Motions in Functional Self-Assembled Nanostructures
Dhôtel, A., Chen, Z., Delbreilh, L., Youssef, B., Saiter, J., & Tan, L. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14022303 · Cited by 75 · see citing works
Fixierung cyclischer Peptide: Mimetika von Proteinstrukturmotiven
Hill, T. A., Shepherd, N. E., Diness, F., & Fairlie, D. P. (2014) · Angewandte Chemie · doi:10.1002/ange.201401058 · Cited by 72 · see citing works
β-Peptides with improved affinity for hDM2 and hDMX
Harker, E. A., Daniels, D. S., Guarracino, D. A., & Schepartz, A. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.01.039 · Cited by 71 · see citing works
Buratto, J., Colombo, C., Stupfel, M., Dawson, S. J., Dolain, C., d’Estaintot, B. L., Fischer, L., Granier, T., Laguerre, M. S., Gallois, B., et al. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201309160 · Cited by 69 · see citing works
Designed Peptides with Homochiral and Heterochiral Diproline Templates as Conformational Constraints
Chatterjee, B., Saha, I., Raghothama, S., Aravinda, S., Rai, R., Shamala, N., & Balaram, P. (2008) · Chemistry - A European Journal · doi:10.1002/chem.200702029 · Cited by 66 · see citing works
Smith, J. M., Vitali, F., Archer, S. A., & Fasan, R. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201101331 · Cited by 65 · see citing works
Self-citationThansandote, P., Harris, R. M., Dexter, H. L., Simpson, G. L., Pal, S., Upton, R. J., & Valko, K. L. (2014) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2014.11.034 · Cited by 61 · see citing works
Stereocontrolled protein surface recognition using chiral oligoamide proteomimetic foldamers
Azzarito, V., Miles, J. A., Fisher, J., Edwards, T. A., Warriner, S. L., & Wilson, A. J. (2015) · Chemical Science · doi:10.1039/c4sc03559c · Cited by 62 · see citing works
β-Hairpin protein epitope mimetic technology in drug discovery
Obrecht, D., Chevalier, É., Moehle, K., & Robinson, J. A. (2011) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2011.07.006 · Cited by 59 · see citing works
Self-citationOrts, J., Wälti, M. A., Marsh, M., Vera, L., Gossert, A. D., Güntert, P., & Riek, R. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.5b12391 · Cited by 57 · see citing works
Ricardo, M. G., Ali, A. M., Plewka, J., Surmiak, E., Łabuzek, B., Neochoritis, C. G., Atmaj, J., Skalniak, Ł., Zhang, R., Holak, T. A., et al. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.201916257 · Cited by 52 · see citing works
Differences in the transactivation domains of p53 family members: a computational study
Mavinahalli, J., Madhumalar, A., Beuerman, R. W., Lane, D. P., & Verma, C. S. (2010) · BMC Genomics · doi:10.1186/1471-2164-11-s1-s5 · Cited by 46 · see citing works
Toxin Neutralization Using Alternative Binding Proteins
Jenkins, T. P., Fryer, T., Dehli, R. I., Jürgensen, J. A., Fuglsang-Madsen, A. J., Føns, S., & Laustsen, A. H. (2019) · Toxins · doi:10.3390/toxins11010053 · Cited by 45 · see citing works
Fujiwara, D., Kitada, H., Oguri, M., Nishihara, T., Michigami, M., Shiraishi, K., Yuba, E., Nakase, I., Im, H., Cho, S., et al. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201603230 · Cited by 44 · see citing works
Selective Targeting of Integrin αvβ8 by a Highly Active Cyclic Peptide
Reichart, F., Maltsev, O. V., Kapp, T. G., Räder, A. F. B., Weinmüller, M., Marelli, U. K., Notni, J., Wurzer, A. J., Beck, R., Wester, H., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01588 · Cited by 43 · see citing works
Li, X., Gohain, N., Chen, S., Li, Y., Zhao, X., Li, B., Tolbert, W. D., He, W., Pazgier, M., Hu, H., et al. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.06.010 · Cited by 44 · see citing works
Frost, J. R., Jacob, N. T., Papa, L. J., Owens, A. E., & Fasan, R. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00119 · Cited by 42 · see citing works
Self-citationPositional effects of click cyclization on β-hairpin structure, stability, and function
Park, J. H., & Waters, M. L. (2012) · Organic & Biomolecular Chemistry · doi:10.1039/c2ob26445e · Cited by 39 · see citing works
Cheng, J., Zhou, J., Kong, L., Wang, H., Zhang, Y., Wang, X., Liu, G., & Chu, Q. (2023) · RSC Medicinal Chemistry · doi:10.1039/d3md00487b · Cited by 39 · see citing works
Ribosomal Synthesis of Natural‐Product‐Like Bicyclic Peptides in Escherichia coli
Bionda, N., & Fasan, R. (2015) · ChemBioChem · doi:10.1002/cbic.201500179 · Cited by 38 · see citing works
Self-citationMax Bergmann lecture Protein epitope mimetics in the age of structural vaccinology
Robinson, J. A. (2013) · Journal of Peptide Science · doi:10.1002/psc.2482 · Cited by 36 · see citing works
Self-citationSmith, J. M., Frost, J. R., & Fasan, R. (2014) · Chemical Communications · doi:10.1039/c4cc01199f · Cited by 37 · see citing works
Self-citationFrost, J. R., Vitali, F., Jacob, N. T., Brown, M. D., & Fasan, R. (2012) · ChemBioChem · doi:10.1002/cbic.201200579 · Cited by 33 · see citing works
Self-citationDesign of Protein–Protein Interaction Inhibitors Based on Protein Epitope Mimetics
Robinson, J. A. (2009) · ChemBioChem · doi:10.1002/cbic.200900055 · Cited by 33 · see citing works
Self-citationDiverse organo-peptide macrocyclesvia a fast and catalyst-free oxime/intein-mediated dual ligation
Maragani, S., Vitali, F., Frost, J. R., & Fasan, R. (2011) · Chemical Communications · doi:10.1039/c1cc13533c · Cited by 31 · see citing works
Self-citationCurrent Trends in Macrocyclic Drug Discovery and beyond -Ro5
Alihodžić, S., Bukvić, M., Elenkov, I., Hutinec, A., Koštrun, S., Pešić, D., Saxty, G., Tomašković, L., & Žiher, D. (2018) · Progress in medicinal chemistry · doi:10.1016/bs.pmch.2018.01.002 · Cited by 31 · see citing works
Headen, T. F., Cullen, P. L., Patel, R., Taylor, A., & Skipper, N. T. (2018) · Physical Chemistry Chemical Physics · doi:10.1039/c7cp06689a · Cited by 28 · see citing works
Comparative validated molecular modeling of p53-HDM2 inhibitors as antiproliferative agents
Mondal, C., Halder, A. K., Adhikari, N., Saha, A., Saha, K. D., Gayen, S., & Jha, T. (2014) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2014.12.011 · Cited by 27 · see citing works
Membranes with Functionalized Nanopores for Aromaticity-Based Separation of Small Molecules
Sadeghi, I., & Asatekin, A. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b00090 · Cited by 26 · see citing works
Wang, Y., Sun, K., Li, J., Guan, X., Zhang, O., Bagni, D., Zhang, Y., Carlson, H. A., & Head-Gordon, T. L. (2025) · Digital Discovery · doi:10.1039/d4dd00357h · Cited by 25 · see citing works
Singh, A. P., Goyal, S., Jamal, S., Subramani, B., Das, M., Admane, N., & Grover, A. (2015) · Structural Chemistry · doi:10.1007/s11224-015-0697-2 · Cited by 24 · see citing works
Danelius, E., Pettersson, M., Bred, M., Min, J., Waddell, M. B., Guy, R. K., Grøtli, M., & Erdélyi, M. (2016) · Organic & Biomolecular Chemistry · doi:10.1039/c6ob01510g · Cited by 24 · see citing works
Marques, J. M. C., Llanio-Trujillo, J. L., Albertí, M., Aguilar, A., & Pirani, F. (2013) · The Journal of Physical Chemistry A · doi:10.1021/jp405295b · Cited by 23 · see citing works
Alkali-Ion Microsolvation with Benzene Molecules
Marques, J. M. C., Llanio-Trujillo, J. L., Albertí, M., Aguilar, A., & Pirani, F. (2012) · The Journal of Physical Chemistry A · doi:10.1021/jp302136u · Cited by 23 · see citing works
Peptide Activators of the p53 Tumor Suppressor
Zhan, C., & Lu, W. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211795222577 · Cited by 23 · see citing works
N-Acylpolyamine inhibitors of HDM2 and HDMX binding to p53
Hayashi, R., Wang, D., Hara, T. J., Iera, J. A., Durell, S. R., & Appella, D. H. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.10.032 · Cited by 22 · see citing works
Aromatic–aromatic interactions in the formation of the MDM2–p53 complex
Espinoza-Fonseca, M., & García‐Machorro, J. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.03.053 · Cited by 22 · see citing works
Buratto, J., Colombo, C., Stupfel, M., Dawson, S. J., Dolain, C., d’Estaintot, B. L., Fischer, L., Granier, T., Laguerre, M. S., Gallois, B., et al. (2013) · Angewandte Chemie · doi:10.1002/ange.201309160 · Cited by 21 · see citing works
A Highly Potent and Cellularly Active β‐Peptidic Inhibitor of the p53/hDM2 Interaction
Hintersteiner, M., Kimmerlin, T., Garavel, G., Schindler, T., Bauer, R., Meisner-Kober, N. C., Seifert, J., Uhl, V., & Auer, M. (2009) · ChemBioChem · doi:10.1002/cbic.200800803 · Cited by 21 · see citing works
Knowledge-Based Virtual Screening: Application to the MDM4/p53 Protein–Protein Interaction
Jacoby, E., Boettcher, A., Mayr, L. M., Brown, N., Jenkins, J. L., Kallen, J. A., Engeloch, C., Schopfer, U., Furet, P., Masuya, K., et al. (2009) · Methods in molecular biology · doi:10.1007/978-1-60761-274-2_7 · Cited by 20 · see citing works
Thomas, E. B., Thankan, R. S., Purushottamachar, P., Weber, D. J., & Njar, V. C. O. (2023) · Cancers · doi:10.3390/cancers15041198 · Cited by 18 · see citing works
Yang, H., Li, S., Li, W., Yang, Y., Zhang, Y., Zhang, S., Yue, H., Cao, W., Xu, F., Wang, H., et al. (2023) · Carcinogenesis · doi:10.1093/carcin/bgad086 · Cited by 18 · see citing works
Verkhivker, G. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040897 · Cited by 18 · see citing works
Strategy and Tactics for Designing Analogs: Biochemical Characterization of the Large Molecules
Ahn, J., Kassees, K., Lee, T.-K., Manandhar, B., & Yousif, A. M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.12413-8 · Cited by 18 · see citing works
Miles, J. A., Hóbor, F., Trinh, C. H., Taylor, J. W., Tiede, C., Rowell, P. R., Jackson, B. R., Nadat, F., Ramsahye, P., Kyle, H. F., et al. (2020) · ChemBioChem · doi:10.1002/cbic.202000585 · Cited by 16 · see citing works
Study of MDM2 Binding to p53-Analogues: Affinity, Helicity, and Applicability to Drug Design
Kalid, O., & Ben‐Tal, N. (2009) · Journal of Chemical Information and Modeling · doi:10.1021/ci800352c · Cited by 17 · see citing works
Temperature dependent structural changes in liquid benzene studied using neutron diffraction
Headen, T. F. (2019) · Molecular Physics · doi:10.1080/00268976.2019.1631496 · Cited by 17 · see citing works
Giant Macrolactams Based on β-Sheet Peptides
Cheng, P.-N., & Nowick, J. S. (2011) · The Journal of Organic Chemistry · doi:10.1021/jo102598n · Cited by 15 · see citing works
Bandyopadhyay, A., Misra, R., & Gopi, H. N. (2016) · Chemical Communications · doi:10.1039/c6cc00127k · Cited by 15 · see citing works
Hetherington, K., Hegedüs, Z., Edwards, T. A., Sessions, R. B., Nelson, A. S., & Wilson, A. J. (2020) · Chemistry - A European Journal · doi:10.1002/chem.202000417 · Cited by 14 · see citing works
Grässlin, A., Amoreira, C., Baldridge, K. K., & Robinson, J. A. (2009) · ChemBioChem · doi:10.1002/cbic.200900008 · Cited by 15 · see citing works
Self-citationGe, Y., Zhang, S., Erdélyi, M., & Voelz, V. A. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.1c00029 · Cited by 14 · see citing works
Carotti, A., Macchiarulo, A., Giacchè, N., & Pellicciari, R. (2009) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22464 · Cited by 13 · see citing works
Smith, J. M., Vitali, F., Archer, S. A., & Fasan, R. (2011) · Angewandte Chemie · doi:10.1002/ange.201101331 · Cited by 13 · see citing works
Self-citationDezi, C., Carotti, A., Magnani, M., Baroni, M., Padova, A., Cruciani, G., Macchiarulo, A., & Pellicciari, R. (2010) · Journal of Chemical Information and Modeling · doi:10.1021/ci100113p · Cited by 12 · see citing works
Structural Effects on ss‐ and dsDNA Recognition by a β‐Hairpin Peptide
Stewart, A. L., & Waters, M. L. (2009) · ChemBioChem · doi:10.1002/cbic.200800524 · Cited by 12 · see citing works
Stabile Peptide statt “gestapelte Peptide”: hochaffine αvβ6‐selektive Integrinliganden
Maltsev, O. V., Marelli, U. K., Kapp, T. G., Leva, F. S. D., Maro, S. D., Nieberler, M., Reuning, U., Schwaiger, M., Novellino, E., Marinelli, L., et al. (2015) · Angewandte Chemie · doi:10.1002/ange.201508709 · Cited by 12 · see citing works
Seitz, M., Rusert, P., Moehle, K., Trkola, A., & Robinson, J. A. (2010) · Chemical Communications · doi:10.1039/c0cc02913k · Cited by 12 · see citing works
Self-citationRamamoorthy, D., Turos, E., & Guida, W. C. (2013) · Journal of Chemical Information and Modeling · doi:10.1021/ci3003528 · Cited by 12 · see citing works
Structure-activity studies of Mdm2/Mdm4-binding stapled peptides comprising non-natural amino acids
Chee, S. M. Q., Wongsantichon, J., Siau, J. W., Thean, D., Ferrer, F. J., Robinson, R. C., Lane, D. P., Brown, C. J., & Ghadessy, F. J. (2017) · PLoS ONE · doi:10.1371/journal.pone.0189379 · Cited by 11 · see citing works
Design and synthesis of functionalized trisaccharides as p53-peptide mimics
Sakurai, K., & Kahne, D. E. (2010) · Tetrahedron Letters · doi:10.1016/j.tetlet.2010.05.012 · Cited by 11 · see citing works
Des agents thérapeutiques ciblant des interactions protéine-protéine
Laudet, B., Prudent, R., Filhol, O., & Cochet, C. (2007) · médecine/sciences · doi:10.1051/medsci/2007233273 · Cited by 10 · see citing works
Anananuchatkul, T., Tsutsumi, H., Miki, T., & Mihara, H. (2020) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2020.127605 · Cited by 9 · see citing works
Aromatic interactions with naphthylalanine in a β‐hairpin peptide
Meyer, D., Mutschler, C., Robertson, I., Batt, A., & Tatko, C. D. (2013) · Journal of Peptide Science · doi:10.1002/psc.2496 · Cited by 10 · see citing works
Conformational stabilization of a β-hairpin through a triazole–tryptophan interaction
Diana, D., Salvo, C. D., Celentano, V., Rosa, L. D., Romanelli, A., Fattorusso, R., & D’Andrea, L. D. (2018) · Organic & Biomolecular Chemistry · doi:10.1039/c7ob02815f · Cited by 9 · see citing works
Diller, D., Swanson, J., Bayden, A. S., Brown, C. J., Thean, D., Lane, D. P., Partridge, A. W., Sawyer, T. K., & Audie, J. (2019) · Molecules · doi:10.3390/molecules24244586 · Cited by 7 · see citing works
Kueh, J. T. B., Choi, K. W., Williams, G. M., Moehle, K., Bacsa, B., Robinson, J. A., & Brimble, M. A. (2013) · Chemistry - A European Journal · doi:10.1002/chem.201204546 · Cited by 7 · see citing works
Self-citationProbing Protein Surfaces: QSAR Analysis with Helix Mimetics
Azzarito, V., Rowell, P. R., Barnard, A., Edwards, T. A., Macdonald, A., Warriner, S. L., & Wilson, A. J. (2015) · ChemBioChem · doi:10.1002/cbic.201500504 · Cited by 7 · see citing works
Macrocyclization and labeling of helix–loop–helix peptide with intramolecular bis‐thioether linkage
Nishihara, T., Kitada, H., Fujiwara, D., & Fujii, I. (2016) · Biopolymers · doi:10.1002/bip.22826 · Cited by 7 · see citing works
Fujiwara, D., Kitada, H., Oguri, M., Nishihara, T., Michigami, M., Shiraishi, K., Yuba, E., Nakase, I., Im, H., Cho, S., et al. (2016) · Angewandte Chemie · doi:10.1002/ange.201603230 · Cited by 7 · see citing works
- Authors
- Fasan, R., Dias, R. L. A., Moehle, K., Zerbe, O., Obrecht, D., Mittl, P. R. E., Grütter, M. G., & Robinson, J. A.
- Affiliations
- University of Zurich (CH)
- Polyphor (Switzerland) (CH)
- Venue
- ChemBioChem
- Publisher
- Wiley
- Published
- 2006-03
- Volume
- 7
- Issue
- 3
- Pages
- 515-526
- ISSN
- 1439-4227 (ISSN-L)
- 1439-7633
- OpenAlex
- W2003327089
- Cited by
- 129
- References
- 84
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 3 · 2017: 3 · 2016: 14 · 2015: 13 · 2014: 8 · 2013: 11 · 2012: 6
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- ChemBioChem (publishedVersion)
- PubMed (publishedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- p53-MDM2 interaction, protein-protein interaction inhibitors, structure-activity relationship, affinity maturation, π-π stacking, X-ray crystal structure, anticancer agents, p53 tumor suppressor
- MeSH terms
- Amino Acid Sequence, Epitopes, Crystallization, Models, Molecular, Protein Binding, Protein Conformation, Structure-Activity Relationship, Tumor Suppressor Protein p53, Molecular Mimicry, Nuclear Magnetic Resonance, Biomolecular, 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