リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Grafting Hydrophobic Amino Acids Critical for Inhibition of Protein–Protein Interactions on a Cell-Penetrating Peptide Scaffold」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Grafting Hydrophobic Amino Acids Critical for Inhibition of Protein–Protein Interactions on a Cell-Penetrating Peptide Scaffold

Nagano, Yuki Arafiles, Jan Vincent V. Kuwata, Keiko Kawaguchi, Yoshimasa Imanishi, Miki Hirose, Hisaaki Futaki, Shiroh 京都大学 DOI:10.1021/acs.molpharmaceut.1c00671

2022.02

概要

Stapled peptides are a promising class of conformationally restricted peptides for modulating protein-protein interactions (PPIs). However, the low membrane permeability of these peptides is an obstacle to their therapeutic applications. It is common that only a few hydrophobic amino acid residues are mandatory for stapled peptides to bind to their target proteins. Hoping to create a novel class of membrane-permeable PPI inhibitors, the phenylalanine, tryptophan, and leucine residues that play a critical role in inhibiting the p53-HDM2 interaction were grafted into the framework of CADY2─a cell-penetrating peptide (CPP) having a helical propensity. Two analogues (CADY-3FWL and CADY-10FWL) induced apoptotic cell death but lacked the intended HDM2 interaction. Pull-down experiments followed by proteomic analysis led to the elucidation of nesprin-2 as a candidate binding target. Nesprin-2 is considered to play a role in the nuclear translocation of β-catenin upon activation of the Wnt signaling pathway, which leads to the expression of antiapoptosis proteins and cell survival. Cells treated with the two analogues showed decreased nuclear localization of β-catenin and reduced mRNA expression of related antiapoptotic proteins. These data suggest inhibition of β-catenin nuclear translocation as a possible mode of action of the described cell-penetrating stapled peptides.

参考文献

(1) Lu, H.; Zhou, Q.; He, J.; Jiang, Z.; Peng, C.; Tong, R.; Shi, J. Recent Advances in the Development of Protein–Protein Interactions Modulators: Mechanisms and Clinical Trials. Signal Transduction and Targeted Therapy. Springer Nature December 1, 2020, pp 1–23.

(2) Pelay-Gimeno, M.; Glas, A.; Koch, O.; Grossmann, T. N. Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes. Angewandte Chemie - International Edition. Wiley-VCH Verlag July 1, 2015, pp 8896–8927.

(3) Verdine, G. L.; Hilinski, G. J. Stapled Peptides for Intracellular Drug Targets. Methods Enzymol. 2012, 503, 3–33.

(4) Grossmann, T. N.; Yeh, J. T. H.; Bowman, B. R.; Chu, Q.; Moellering, R. E.; Verdine, G. L. Inhibition of Oncogenic Wnt Signaling through Direct Targeting of β-Catenin. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 17942–17947.

(5) Cromm, P. M.; Spiegel, J.; Grossmann, T. N. Hydrocarbon Stapled Peptides as Modulators of Biological Function. ACS Chemical Biology. American Chemical Society June 19, 2015, pp 1362–1375.

(6) Walensky, L. D.; Bird, G. H. Hydrocarbon-Stapled Peptides: Principles, Practice, and Progress. Journal of Medicinal Chemistry. American Chemical Society August 14, 2014, pp 6275–6288.

(7) Martinek, T. A.; Fülöp, F. Peptidic Foldamers: Ramping up Diversity. Chem. Soc. Rev. 2012, 41, 687–702.

(8) Sun, T.-L.; Sun, Y.; Lee, C.-C.; Huang, H. W. Membrane Permeability of Hydrocarbon-Cross-Linked Peptides. Biophys. J. 2013, 104, 1923–1932.

(9) Sakagami, K.; Masuda, T.; Kawano, K.; Futaki, S. Importance of Net Hydrophobicity in the Cellular Uptake of All-Hydrocarbon Stapled Peptides. Mol. Pharm. 2018, 15, 1332–1340.

(10) Bernal, F.; Tyler, A. F.; Korsmeyer, S. J.; Walensky, L. D.; Verdine, G. L. Reactivation of the P53 Tumor Suppressor Pathway by a Stapled P53 Peptide. J. Am. Chem. Soc. 2007, 129, 2456–2457.

(11) Dietrich, L.; Rathmer, B.; Ewan, K.; Bange, T.; Heinrichs, S.; Dale, T. C.; Schade, D.; Grossmann, T. N. Cell Permeable Stapled Peptide Inhibitor of Wnt Signaling That Targets β-Catenin Protein-Protein Interactions. Cell Chem. Biol. 2017, 24, 958-968.e5.

(12) Bird, G. H.; Mazzola, E.; Opoku-Nsiah, K.; Lammert, M. A.; Godes, M.; Neuberg, D. S.; Walensky, L. D. Biophysical Determinants for Cellular Uptake of Hydrocarbon-Stapled Peptide Helices. Nat. Chem. Biol. 2016, 12, 845–852.

(13) Young, L.; Jernigan, R. L.; Covell, D. G. A Role for Surface Hydrophobicity in Protein‐protein Recognition. Protein Sci. 1994, 3, 717–729.

(14) Yan, C.; Wu, F.; Jernigan, R. L.; Dobbs, D.; Honavar, V. Characterization of Protein-Protein Interfaces. Protein J. 2008, 27, 59–70.

(15) Chang, Y. S.; Graves, B.; Guerlavais, V.; Tovar, C.; Packman, K.; To, K. H.; Olson, K. A.; Kesavan, K.; Gangurde, P.; Mukherjee, A.; Baker, T.; Darlak, K.; Elkin, C.; Filipovic, Z.; Qureshi, F. Z.; Cai, H.; Berry, P.; Feyfant, E.; Shi, X. E.; Horstick, J.; Annis, D. A.; Manning, A. M.; Fotouhi, N.; Nash, H.; Vassilev, L. T.; Sawyer, T. K. Stapled α-Helical Peptide Drug Development: A Potent Dual Inhibitor of MDM2 and MDMX for P53-Dependent Cancer Therapy. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, E3445–E3454.

(16) Yuen, T. Y.; Brown, C. J.; Xue, Y.; Tan, Y. S.; Ferrer Gago, F. J.; Lee, X. E.; Neo, J. Y.; Thean, D.; Kaan, H. Y. K.; Partridge, A. W.; Verma, C. S.; Lane, D. P.; Johannes, C. W. Stereoisomerism of Stapled Peptide Inhibitors of the P53-Mdm2 Interaction: An Assessment of Synthetic Strategies and Activity Profiles. Chem. Sci. 2019, 10, 6457–6466.

(17) Shi, Y.; Sang, P.; Lu, J.; Higbee, P.; Chen, L.; Yang, L.; Odom, T.; Daughdrill, G.; Chen, J.; Cai, J. Rational Design of Right-Handed Heterogeneous Peptidomimetics as Inhibitors of Protein-Protein Interactions. J. Med. Chem. 2020, 63, 13187– 13196.

(18) Ben-Nun, Y.; Seo, H.-S.; Harvey, E. P.; Hauseman, Z. J.; Wales, T. E.; Newman, C. E.; Cathcart, A. M.; Engen, J. R.; Dhe-Paganon, S.; Walensky, L. D. Identification of a Structural Determinant for Selective Targeting of HDMX. Structure 2020, 28, 847-857.e5.

(19) Wójcik, P.; Berlicki, Ł. Peptide-Based Inhibitors of Protein-Protein Interactions. Bioorganic and Medicinal Chemistry Letters. Elsevier Ltd February 1, 2016, pp 707–713.

(20) Kritzer, J. A.; Zutshi, R.; Cheah, M.; Ran, F. A.; Webman, R.; Wongjirad, T. M.; Schepartz, A. Miniature Protein Inhibitors of the P53-HDM2 Interaction. ChemBioChem 2006, 7, 29–31.

(21) Ji, Y.; Majumder, S.; Millard, M.; Borra, R.; Bi, T.; Elnagar, A. Y.; Neamati, N.; Shekhtman, A.; Camarero, J. A. In Vivo Activation of the P53 Tumor Suppressor Pathway by an Engineered Cyclotide. J. Am. Chem. Soc. 2013, 135, 11623–11633.

(22) Fujiwara, D.; Kitada, H.; Oguri, M.; Nishihara, T.; Michigami, M.; Shiraishi, K.; Yuba, E.; Nakase, I.; Im, H.; Cho, S.; Joung, J. Y.; Kodama, S.; Kono, K.; Ham, S.; Fujii, I. A Cyclized Helix-Loop-Helix Peptide as a Molecular Scaffold for the Design of Inhibitors of Intracellular Protein-Protein Interactions by Epitope and Arginine Grafting. Angew. Chemie Int. Ed. 2016, 55, 10612–10615.

(23) Li, C.; Liu, M.; Monbo, J.; Zou, G.; Li, C.; Yuan, W.; Zella, D.; Lu, W. Y.; Lu, W. Turning a Scorpion Toxin into an Antitumor Miniprotein. J. Am. Chem. Soc. 2008, 130, 13546–13548.

(24) Ricardo, M. G.; Ali, A. M.; Plewka, J.; Surmiak, E.; Labuzek, B.; Neochoritis, C. G.; Atmaj, J.; Skalniak, L.; Zhang, R.; Holak, T. A.; Groves, M.; Rivera, D. G.; Dömling, A. Multicomponent Peptide Stapling as a Diversity-Driven Tool for the Development of Inhibitors of Protein–Protein Interactions. Angew. Chemie - Int. Ed. 2020, 59, 5235–5241.

(25) Rosenfeld, J.; Capdevielle, J.; Guillemot, J. C.; Ferrara, P. In-Gel Digestion of Proteins for Internal Sequence Analysis after One- or Two-Dimensional Gel Electrophoresis. Anal. Biochem. 1992, 203, 173–179.

(26) Schindelin, J.; Arganda-Carreras, I.; Frise, E.; Kaynig, V.; Longair, M.; Pietzsch, T.; Preibisch, S.; Rueden, C.; Saalfeld, S.; Schmid, B.; Tinevez, J. Y.; White, D. J.; Hartenstein, V.; Eliceiri, K.; Tomancak, P.; Cardona, A. Fiji: An Open-Source Platform for Biological-Image Analysis. Nat. Methods 2012, 9, 676–682.

(27) Klein, C.; Vassilev, L. T. Targeting the P53-MDM2 Interaction to Treat Cancer. British Journal of Cancer. Nature Publishing Group October 18, 2004, pp 1415– 1419.

(28) Kussie, P. H.; Gorina, S.; Marechal, V.; Elenbaas, B.; Moreau, J.; Levine, A. J.; Pavletich, N. P. Structure of the MDM2 Oncoprotein Bound to the P53 Tumor Suppressor Transactivation Domain. Science (80-. ). 1996, 274, 948–953.

(29) Lin, J.; Chen, J.; Elenbaas, B.; Levine, A. J. Several Hydrophobic Amino Acids in the P53 Amino-Terminal Domain Are Required for Transcriptional Activation, Binding to Mdm-2 and the Adenovirus 5 E1B 55-KD Protein. Genes Dev. 1994, 8, 1235–1246.

(30) Baek, S.; Kutchukian, P. S.; Verdine, G. L.; Huber, R.; Holak, T. A.; Lee, K. W.; Popowicz, G. M. Structure of the Stapled P53 Peptide Bound to Mdm2. J. Am. Chem. Soc. 2012, 134, 103–106.

(31) Kurzawa, L.; Pellerano, M.; Morris, M. C. PEP and CADY-Mediated Delivery of Fluorescent Peptides and Proteins into Living Cells. Biochim. Biophys. Acta - Biomembr. 2010, 1798, 2274–2285.

(32) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. Efficient and Recyclable Monomeric and Dendritic Ru-Based Metathesis Catalysts. J. Am. Chem. Soc. 2000, 122, 8168–8179.

(33) Matsuoka, M.; Wispriyono, B.; Igisu, H. Increased Cytotoxicity of Cadmium in Fibroblasts Lacking C-Fos. Biochem. Pharmacol. 2000, 59, 1573–1576.

(34) Li, J.; Yuan, J. Caspases in Apoptosis and Beyond. Oncogene 2008, 27, 6194–6206.

(35) Ward, T. H.; Cummings, J.; Dean, E.; Greystoke, A.; Hou, J. M.; Backen, A.; Ranson, M.; Dive, C. Biomarkers of Apoptosis. Br. J. Cancer 2008, 99, 841–846.

(36) Logue, S. E.; Elgendy, M.; Martin, S. J. Expression, Purification and Use of Recombinant Annexin V for the Detection of Apoptotic Cells. Nat. Protoc. 2009, 4, 1383–1395.

(37) Zhang, Q.; Minaisah, R. M.; Ferraro, E.; Li, C.; Porter, L. J.; Zhou, C.; Gao, F.; Zhang, J.; Rajgor, D.; Autore, F.; Shanahan, C. M.; Warren, D. T. N-Terminal Nesprin-2 Variants Regulate β-Catenin Signalling. Exp. Cell Res. 2016, 345, 168– 179.

(38) Chen, S.; Guttridge, D. C.; You, Z.; Zhang, Z.; Fribley, A.; Mayo, M. W.; Kitajewski, J.; Wang, C. Y. Wnt-1 Signaling Inhibits Apoptosis by Activating β- Catenin/T Cell Factor-Mediated Transcription. J. Cell Biol. 2001, 152, 87–96.

(39) Kim, E.; Lisby, A.; Ma, C.; Lo, N.; Ehmer, U.; Hayer, K. E.; Furth, E. E.; Viatour, P. Promotion of Growth Factor Signaling as a Critical Function of β-Catenin during HCC Progression. Nat. Commun. 2019, 10, 1–17.

(40) Clevers, H.; Nusse, R. Wnt/β-Catenin Signaling and Disease. Cell 2012, 149, 1192–1205.

(41) Willert, J.; Epping, M.; Pollack, J. R.; Brown, P. O.; Nusse, R. A Transcriptional Response to Wnt Protein in Human Embryonic Carcinomacells. BMC Dev. Biol. 2002, 2, 1–7.

(42) Jho, E. H.; Lomvardas, S.; Costantini, F. A GSK3β Phosphorylation Site in Axin Modulates Interaction with β-Catenin and Tcf-Mediated Gene Expression. Biochem. Biophys. Res. Commun. 1999, 266, 28–35.

(43) Tajadura, V.; Hansen, M. H.; Smith, J.; Charles, H.; Rickman, M.; Farrell-Dillon, K.; Claro, V.; Warboys, C.; Ferro, A. β-Catenin Promotes Endothelial Survival by Regulating ENOS Activity and Flow-Dependent Anti-Apoptotic Gene Expression. Cell Death Dis. 2020, 11, 1–16.

(44) Mikhailov, V.; Mikhailova, M.; Pulkrabek, D. J.; Dong, Z.; Venkatachalam, M. A.; Saikumar, P. Bcl-2 Prevents Bax Oligomerization in the Mitochondrial Outer Membrane. J. Biol. Chem. 2001, 276, 18361–18374.

(45) Marie Hardwick, J.; Soane, L. Multiple Functions of BCL-2 Family Proteins. Cold Spring Harb. Perspect. Biol. 2013, 5.

(46) Garg, H.; Suri, P.; Gupta, J. C.; Talwar, G. P.; Dubey, S. Survivin: A Unique Target for Tumor Therapy. Cancer Cell Int. 2016, 16, 49.

(47) Czabotar, P. E.; Lessene, G.; Strasser, A.; Adams, J. M. Control of Apoptosis by the BCL-2 Protein Family: Implications for Physiology and Therapy. Nat. Rev. Mol. Cell Biol. 2014, 15, 49–63.

(48) Mihara, E.; Hirai, H.; Yamamoto, H.; Tamura-Kawakami, K.; Matano, M.; Kikuchi, A.; Sato, T.; Takagi, J. Active and Water-Soluble Form of Lipidated Wnt Protein Is Maintained by a Serum Glycoprotein Afamin/α-Albumin. Elife 2016, 5.

(49) Kelkar, P.; Walter, A.; Papadopoulos, S.; Mroß, C.; Munck, M.; Peche, V. S.; Noegel, A. A. Nesprin-2 Mediated Nuclear Trafficking and Its Clinical Implications. Nucleus 2015, 6, 479–489.

参考文献をもっと見る