High-affinity binders selected from designed ankyrin repeat protein libraries
Abstract
We report here the evolution of ankyrin repeat (AR) proteins in vitro for specific, high-affinity target binding. Using a consensus design strategy, we generated combinatorial libraries of AR proteins of varying repeat numbers with diversified binding surfaces. Libraries of two and three repeats, flanked by 'capping repeats,' were used in ribosome-display selections against maltose binding protein (MBP) and two eukaryotic kinases. We rapidly enriched target-specific binders with affinities in the low nanomolar range and determined the crystal structure of one of the selected AR proteins in complex with MBP at 2.3 A resolution. The interaction relies on the randomized positions of the designed AR protein and is comparable to natural, heterodimeric protein-protein interactions. Thus, our AR protein libraries are valuable sources for binding molecules and, because of the very favorable biophysical properties of the designed AR proteins, an attractive alternative to antibody libraries.
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POI-targeting polypeptides can either be single chain antibodies (e.g. nanobodies) or a variety of synthetic polypeptide scaffolds that bind POIs such as monobodies, DARPINs, affimers, or Affibodies.
“These POI-targeting polypeptides can either be single chain antibodies (e.g. variable domains from camelid or shark-derived heavy chain only antibodies, nanobodies), or a variety of synthetic polypeptide scaffolds that bind POIs such as fibronectin type III domain-based monobodies [110, 111], designed ankyrin repeats (DARPINs) [112, 113], cystatin-derived affimers [114] or Affibodies derived from”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [113]
Cites
1 retracted
Fluorobodies combine GFP fluorescence with the binding characteristics of antibodies
Zeytun, A., Jeromin, A., Scalettar, B. A., Waldo, G. S., & Bradbury, A. M. (2003) · Nature Biotechnology · doi:10.1038/nbt911 · Cited by 31 · see citing works
RetractedMolecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Molecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684 · see citing works
The CCP4 suite: programs for protein crystallography
Number Collaborative Computational Project (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994003112 · Cited by 17,299 · see citing works
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse‐Kunstleve, R. W., Jiang, J., Kuszewski, J. J., Nilges, M., Pannu, N., et al. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998003254 · Cited by 15,720 · see citing works
Jones, T. A., Zou, J.-Y., Cowan, S. W., & Kjeldgaard, M. (1991) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767390010224 · Cited by 12,650 · see citing works
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
LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions
Wallace, A. C., Laskowski, R. A., & Thornton, J. M. (1995) · Protein Engineering Design and Selection · doi:10.1093/protein/8.2.127 · Cited by 5,705 · 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
AMoRe: an automated package for molecular replacement
Navaza, J. (1994) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767393007597 · Cited by 4,941 · see citing works
Principles of protein-protein interactions
Jones, S., & Thornton, J. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.1.13 · Cited by 2,684 · see citing works
Satisfying Hydrogen Bonding Potential in Proteins
McDonald, I. K., & Thornton, J. M. (1994) · Journal of Molecular Biology · doi:10.1006/jmbi.1994.1334 · Cited by 2,136 · 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
In vitro selection and evolution of functional proteins by using ribosome display
Hanes, J., & Plückthun, A. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.4937 · Cited by 1,090 · see citing works
Self-citationWinter, G., & Milstein, C. (1991) · Nature · doi:10.1038/349293a0 · Cited by 946 · see citing works
The ankyrin repeat: a diversity of interactions on a common structural framework
Sedgwick, S. G., & Smerdon, S. J. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01426-7 · Cited by 823 · see citing works
Antibody Multispecificity Mediated by Conformational Diversity
James, L. C., Roversi, P., & Tawfik, D. S. (2003) · Science · doi:10.1126/science.1079731 · Cited by 719 · see citing works
Structure, function and evolution of plant disease resistance genes
Ellis, J. G., Dodds, P. N., & Pryor, T. (2000) · Current Opinion in Plant Biology · doi:10.1016/s1369-5266(00)00080-7 · Cited by 619 · see citing works
Protein Repeats: Structures, Functions, and Evolution
Andrade-Navarro, M. A., Perez‐Iratxeta, C., & Ponting, C. P. (2001) · Journal of Structural Biology · doi:10.1006/jsbi.2001.4392 · Cited by 613 · see citing works
Binz, H. K., Stumpp, M. T., Forrer, P., Amstutz, P., & Plückthun, A. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00896-9 · Cited by 589 · see citing works
Self-citationPeer Bork, B. (1993) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340170405 · Cited by 512 · see citing works
Structure, function and properties of antibody binding sites
Mian, S. I., Bradwell, A. R., & Olson, A. J. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)90617-f · Cited by 442 · see citing works
Marcotte, E. M., Pellegrini, M. A., Yeates, T. O., & Eisenberg, D. S. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3136 · Cited by 412 · see citing works
Hanes, J., Schaffitzel, C., Knappik, A., & Plückthun, A. (2000) · Nature Biotechnology · doi:10.1038/82407 · Cited by 373 · see citing works
Self-citationConsensus-derived structural determinants of the ankyrin repeat motif
Mosavi, L. K., Minor, D. L., & Peng, Z. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252537899 · Cited by 360 · see citing works
Topological characteristics of helical repeat protein
Groves, M. R., & Barford, D. (1999) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(99)80052-9 · Cited by 331 · see citing works
When protein folding is simplified to protein coiling: the continuum of solenoid protein structures
Kobe, B., & Kajava, A. V. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01667-4 · Cited by 281 · see citing works
Designed to be stable: Crystal structure of a consensus ankyrin repeat protein
Kohl, A., Binz, H. K., Forrer, P., Stumpp, M. T., Plückthun, A., & Grütter, M. G. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0337680100 · Cited by 279 · see citing works
Self-citationDesign of Stable α-Helical Arrays from an Idealized TPR Motif
Main, E. R. G., Xiong, Y., Cocco, M. J., D’Andrea, L. D., & Regan, L. (2003) · Structure · doi:10.1016/s0969-2126(03)00076-5 · Cited by 274 · see citing works
Molecular recognition in antibody-antigen complexes
Sundberg, E. J., & Mariuzza, R. A. (2002) · Advances in protein chemistry · doi:10.1016/s0065-3233(02)61004-6 · Cited by 255 · see citing works
Directed Evolution of High-Affinity Antibody Mimics Using mRNA Display
Xu, L., Aha, P., Gu, K., Kuimelis, R. G., Kurz, M., Lam, T., Lim, A. C., Liu, H., Lohse, P. A., Sun, L., et al. (2002) · Chemistry & Biology · doi:10.1016/s1074-5521(02)00187-4 · Cited by 252 · see citing works
Hon, W., McKay, G. A., Thompson, P. R., Sweet, R. M., Yang, D. S. C., Wright, G. D., & Berghuis, A. M. (1997) · Cell · doi:10.1016/s0092-8674(00)80274-3 · Cited by 241 · see citing works
Structural basis of inhibition of CDK–cyclin complexes by INK4 inhibitorsPreprint
Jeffrey, P. D., Tong, L., & Pavletich, N. P. (2000) · Genes & Development · doi:10.1101/gad.851100 · Cited by 239 · see citing works
Engineered protein scaffolds for molecular recognition
Skerra, A. (2000) · Journal of Molecular Recognition · doi:10.1002/1099-1352(200007/08)13:4 · Cited by 236 · see citing works
Tailoring in vitro evolution for protein affinity or stability
Jermutus, L., Honegger, A., Schwesinger, F., Hanes, J., & Plückthun, A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.75 · Cited by 233 · see citing works
Self-citationCLAMP©: a biosensor kinetic data analysis program
Myszka, D. G., & Morton, T. A. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01183-9 · Cited by 216 · see citing works
Fv fragment-mediated crystallization of the membrane protein bacterial cytochrome c oxidase
Ostermeier, C., Iwata, S., Ludwig, B., & Michel, H. (1995) · Nature Structural Biology · doi:10.1038/nsb1095-842 · Cited by 180 · see citing works
Structural basis of macromolecular recognition
Wodak, S. J., & Janin, J. (2002) · Advances in protein chemistry · doi:10.1016/s0065-3233(02)61001-0 · Cited by 172 · see citing works
Novel fold and capsid-binding properties of the lambda-phage display platform protein gpD.
Plückthun, A., Yang, F., Forrer, P., Dauter, Z., Conway, J. F., Cheng, N., Cerritelli, M. E., Steven, A. C., & Wlodawer, A. (2000) · Nature Structural Biology · doi:10.1038/73347 · Cited by 168 · see citing works
Self-citationMalek, S., Huxford, T., & Ghosh, G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.39.25427 · Cited by 153 · see citing works
A novel strategy to design binding molecules harnessing the modular nature of repeat proteins
Forrer, P., Stumpp, M. T., Binz, H. K., & Plückthun, A. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00177-7 · Cited by 151 · see citing works
Self-citationScaffolds for engineering novel binding sites in proteins
Nygren, P., & Uhlén, M. (1997) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(97)80108-x · Cited by 149 · see citing works
The selection of intracellular antibodies
Cattaneo, A., & Biocca, S. (1999) · Trends in biotechnology · doi:10.1016/s0167-7799(98)01268-2 · Cited by 148 · see citing works
An affibody in complex with a target protein: Structure and coupled folding
Wahlberg, E., Lendel, C., Helgstrand, M., Allard, P., Dinçbas‐Renqvist, V., Hedqvist, A., Berglund, H., Nygren, P., & Härd, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0436086100 · Cited by 119 · see citing works
Detection and Characterization of Xenon-binding Sites in Proteins by 129Xe NMR Spectroscopy
Rubin, S. M., Lee, S., Ruiz, E. J., Pines, A., & Wemmer, D. E. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00739-8 · Cited by 113 · see citing works
Structural basis for recognition by an in vitro evolved affibody
Högbom, M., Eklund, M., Nygren, P., & Nordlund, P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0436100100 · Cited by 104 · see citing works
Anti‐idiotypic protein domains selected from protein A‐based affibody libraries
Eklund, M., Axelsson, L., Uhlén, M., & Nygren, P. (2002) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.10169 · Cited by 83 · see citing works
Imitating the humoral immune response
Skerra, A. (2003) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2003.10.012 · Cited by 55 · see citing works
Functional Interactions of Transcription Factor Human GA-binding Protein Subunits
Suzuki, F., Goto, M., Sawa, C., Ito, S., Watanabe, H., Sawada, J.-I., & Handa, H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.45.29302 · Cited by 46 · see citing works
Enzyme-Linked Immunosorbent Assay for Measurement of JNK, ERK, and p38 Kinase Activities
Forrer, P., Tamaskovic, R., & Jaussi, R. (1998) · Biological Chemistry · doi:10.1515/bchm.1998.379.8-9.1101 · Cited by 43 · see citing works
Self-citationJJroducing antibodies in Escherichia coli: from PCR to fermentation
Plückthun, A., Krebber, A., Krebber, C., Horn, U., Knüpfer, U., Wenderoth, R., Nieba, L., Proba, K., & Riesenberg, D. (1996) · doi:10.1093/oso/9780199635924.003.0010 · Cited by 43 · see citing works
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Tanenbaum, M. E., Gilbert, L. A., Qi, L. S., Weissman, J. S., & Vale, R. D. (2014) · Cell · doi:10.1016/j.cell.2014.09.039 · Cited by 1,559 · see citing works
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Dunn, M. R., Jimenez, R. M., & Chaput, J. C. (2017) · Nature Reviews Chemistry · doi:10.1038/s41570-017-0076 · Cited by 938 · see citing works
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Binz, H. K., Amstutz, P., & Plückthun, A. (2005) · Nature Biotechnology · doi:10.1038/nbt1127 · Cited by 676 · see citing works
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Li, J., Mahajan, A., & Tsai, M. (2006) · Biochemistry · doi:10.1021/bi062188q · Cited by 651 · see citing works
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Rich, R. L., & Myszka, D. G. (2004) · Journal of Molecular Recognition · doi:10.1002/jmr.726 · Cited by 505 · see citing works
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Mascini, M., Palchetti, I., & Tombelli, S. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201006630 · Cited by 375 · see citing works
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Self-citationIn Search of the Hair-Cell Gating Spring
Sotomayor, M. M., Corey, D. P., & Schulten, K. J. (2005) · Structure · doi:10.1016/j.str.2005.03.001 · Cited by 267 · see citing works
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Self-citationZahnd, C., Kawe, M., Stumpp, M. T., de Pasquale, C., Tamaskovic, R., Nagy‐Davidescu, G., Dreier, B., Schibli, R., Binz, H. K., Waibel, R., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-2724 · Cited by 245 · see citing works
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Björklund, Å. K., Ekman, D. S., & Elofsson, A. (2006) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0020114 · Cited by 244 · see citing works
Taussig, M., Stoevesandt, O., Borrebaeck, C. A. K., Bradbury, A. M., Cahill, D. J., Cambillau, C., de Daruvar, A., Dübel, S., Eichler, J., Frank, R., et al. (2006) · Nature Methods · doi:10.1038/nmeth0107-13 · Cited by 236 · see citing works
Self-citationKoide, A., Wojcik, J., Gilbreth, R. N., Hoey, R. J., & Koide, S. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.12.019 · Cited by 227 · see citing works
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Koide, S., & Sidhu, S. S. (2009) · ACS Chemical Biology · doi:10.1021/cb800314v · Cited by 216 · see citing works
Steiner, D., Forrer, P., Stumpp, M. T., & Plückthun, A. (2006) · Nature Biotechnology · doi:10.1038/nbt1218 · Cited by 215 · see citing works
Self-citationA new generation of protein display scaffolds for molecular recognition
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Münch, R. C., Janicki, H., Völker, I., Rasbach, A., Hallek, M. J., Büning, H., & Buchholz, C. J. (2012) · Molecular Therapy · doi:10.1038/mt.2012.186 · Cited by 176 · see citing works
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Lee, S., Park, K., Han, J., Lee, J., Kim, H. S., Hong, S. P., Heu, W., Kim, Y. J., Ha, J., Lee, S., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113193109 · Cited by 146 · see citing works
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Mujtaba, J., Liu, J., Dey, K. K., Li, T., Chakraborty, R., Xu, K., Makarov, D., Barmin, R. A., Gorin, D. A., Tolstoy, V. P., et al. (2021) · Advanced Materials · doi:10.1002/adma.202007465 · Cited by 121 · see citing works
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Sikorski, A. F., Toporkiewicz, M., Meissner, J. M., Matusewicz, L., & Czogalla, A. (2015) · International Journal of Nanomedicine · doi:10.2147/ijn.s74514 · Cited by 104 · see citing works
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Kummer, L., Parizek, P., Rube, P., Millgramm, B., Prinz, A., Mittl, P. R. E., Kaufholz, M., Zimmermann, B., Herberg, F. W., & Plückthun, A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205399109 · Cited by 101 · see citing works
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Urvoas, A., Guellouz, A., Valerio‐Lepiniec, M., Graille, M., Christiane, D. D., Desravines, D. C., TILBEURGH, H. V., Desmadril, M., & Minard, P. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.09.048 · Cited by 100 · see citing works
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Gilbreth, R. N., & Koide, S. (2012) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2012.06.001 · Cited by 98 · see citing works
Ferreiro, D. U., Cho, S. S., Komives, E. A., & Wolynes, P. G. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.09.078 · Cited by 96 · see citing works
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Röth, S., Fulcher, L. J., & Sapkota, G. P. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03112-6 · Cited by 92 · see citing works
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Mouratou, B., Schaeffer, F., Guilvout, I., Tello, D., Pugsley, A. P., Alzari, P. M., & Pecorari, F. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702963104 · Cited by 93 · see citing works
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Kloss, E., Courtemanche, N., & Barrick, D. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.08.034 · Cited by 91 · see citing works
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Park, K., Shen, B. W., Parmeggiani, F., Huang, P., Stoddard, B. L., & Baker, D. A. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2938 · Cited by 90 · see citing works
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Goldstein, R., Sosabowski, J. K., Livanos, M., Leyton, J., Vigor, K., Bhavsar, G., Nagy‐Davidescu, G., Rashid, M., Miranda, E., Yeung, J., et al. (2014) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-014-2940-2 · Cited by 91 · see citing works
Self-citation
- Authors
- Binz, H. K., Amstutz, P., Kohl, A., Stumpp, M. T., Briand, C., Forrer, P., Grütter, M. G., & Plückthun, A.
- Affiliations
- University of Zurich (CH)
- Corresponding author
- Grütter, Markus G
- Plückthun, Andreas
- Venue
- Nature Biotechnology
- Published
- 2004-04-18
- Volume
- 22
- Issue
- 5
- Pages
- 575-582
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2084938664
- Cited by
- 656
- References
- 51
- Citations by year
- 2026: 7 · 2025: 22 · 2024: 17 · 2023: 26 · 2022: 27 · 2021: 23 · 2020: 31 · 2019: 24 · 2018: 22 · 2017: 38 · 2016: 28 · 2015: 36 · 2014: 33 · 2013: 33 · 2012: 35
- FWCI
- 30.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- National Center of Competence in Research Chemical Biology
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- ankyrin repeat proteins, combinatorial protein libraries, ribosome display, protein-protein interaction, maltose-binding protein, high-affinity binders, consensus design, protein crystal structure
- MeSH terms
- Amino Acid Sequence, Enzyme-Linked Immunosorbent Assay, Molecular Sequence Data, Protein Conformation, Ankyrin Repeat
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