Production of cyclic peptides and proteins in vivo
Open accessAbstract
Combinatorial libraries of synthetic and natural products are an important source of molecular information for the interrogation of biological targets. Methods for the intracellular production of libraries of small, stable molecules would be a valuable addition to existing library technologies by combining the discovery potential inherent in small molecules with the large library sizes that can be realized by intracellular methods. We have explored the use of split inteins ( in ternal pro teins ) for the intracellular catalysis of peptide backbone cyclization as a method for generating proteins and small peptides that are stabilized against cellular catabolism. The DnaE split intein from Synechocystis sp. PCC6803 was used to cyclize the Escherichia coli enzyme dihydrofolate reductase and to produce the cyclic, eight-amino acid tyrosinase inhibitor pseudostellarin F in bacteria. Cyclic dihydrofolate reductase displayed improved in vitro thermostability, and pseudostellarin F production was readily apparent in vivo through its inhibition of melanin production catalyzed by recombinant Streptomyces antibioticus tyrosinase. The ability to generate and screen for backbone cyclic products in vivo is an important milestone toward the goal of generating intracellular cyclic peptide and protein libraries.
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Cites
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 Chemist's Companion: A Handbook of Practical Data, Techniques, and References
Gordon, A. J., & Ford, R. A. (1972) · Medical Entomology and Zoology · Cited by 1,857 · see citing works
A bacterial two-hybrid system based on a reconstituted signal transduction pathway
Karimova, G., Pidoux, J., Ullmann, A., & Ladant, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.10.5752 · Cited by 1,664 · see citing works
Method for Determination of the Amino Acid Sequence in Peptides.
Edman, P., Högfeldt, E., Sillén, L. G., & Kinell, P. (1950) · Acta chemica Scandinavica/Acta chemica Scandinavica. B, Organic chemistry and biochemistry/Acta chemica Scandinavica. A, Physical and inorganic chemistry/Acta chemica Scandinavica. Series B. Organic chemistry and biochemistry/Acta chemica Scandinavica. Series A, Physical and inorganic chemistry · doi:10.3891/acta.chem.scand.04-0283 · Cited by 1,398 · see citing works
Gordon, E. M., Barrett, R. W., Dower, W. J., Fodor, S. P. A., & Gallop, M. A. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00036a001 · Cited by 1,142 · see citing works
Gallop, M. A., Barrett, R. W., Dower, W. J., Fodor, S. P. A., & Gordon, E. M. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00035a001 · Cited by 1,135 · see citing works
Xu, Y. Q., Piston, D. W., & Johnson, C. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.1.151 · Cited by 613 · see citing works
McDaniel, R. N., Thamchaipenet, A., Gustafsson, C., Fu, H., Betlach, M. C., Betlach, M. C., & Ashley, G. W. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.1846 · Cited by 463 · see citing works
Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2
Colas, P., Cohen, B. A., Jessen, T., Grishina, I. A., McCoy, J. M., & Brent, R. (1996) · Nature · doi:10.1038/380548a0 · Cited by 459 · see citing works
Protein trans -splicing by a split intein encoded in a split DnaE gene of Synechocystis sp. PCC6803
Wu, H., Hu, Z., & Liu, X. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9226 · Cited by 379 · see citing works
Rossi, F. M. V., Charlton, C. A., & Blau, H. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.16.8405 · Cited by 323 · see citing works
Aptamers as therapeutic and diagnostic reagents: problems and prospects
Osborne, S. E. (1997) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(97)80102-0 · Cited by 289 · see citing works
Compilation and analysis of intein sequences
Perler, F. B. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.6.1087 · Cited by 202 · see citing works
Genetic Selection of Peptide Inhibitors of Biological Pathways
Norman, T., Smith, D. L., Sorger, P. K., Drees, B., O’Rourke, S. M., Hughes, T. R., Roberts, C. J., Friend, S. H., Fields, S., & Murray, A. W. (1999) · Science · doi:10.1126/science.285.5427.591 · Cited by 190 · see citing works
Folded proteins occur frequently in libraries of random amino acid sequences.
Davidson, A. R., & Sauer, R. T. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.6.2146 · Cited by 185 · see citing works
Bernan, V. S., Filpula, D. R., Herber, W. K., Bibb, M. J., & Katz, E. (1985) · Gene · doi:10.1016/0378-1119(85)90262-8 · Cited by 168 · see citing works
An in vivo library-versus-library selection of optimized protein–protein interactions
Pelletier, J. N., Arndt, K. M., Plückthun, A., & Michnick, S. W. (1999) · Nature Biotechnology · doi:10.1038/10897 · Cited by 166 · see citing works
Biosynthesis of a Head-to-Tail Cyclized Protein with Improved Biological Activity
Camarero, J. A., & Muir, T. W. (1999) · Journal of the American Chemical Society · doi:10.1021/ja990929n · Cited by 146 · see citing works
Dimitrova, M., Younès-Cauet, G., Oertel‐Buchheit, P., Porte, D., Granger‐Schnarr, M., & Schnarr, M. (1998) · Molecular and General Genetics MGG · doi:10.1007/s004380050640 · Cited by 139 · see citing works
Evans, T. C., Benner, J., & Xu, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.26.18359 · Cited by 134 · see citing works
Combinatorial protein engineering by incremental truncation
Ostermeier, M., Nixon, A. E., Shim, J. H., & Benkovic, S. J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3562 · Cited by 131 · see citing works
Self-citation“Mutagenesis” by peptide aptamers identifies genetic network members and pathway connections
Geyer, C. R., Colman‐Lerner, A., & Brent, R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.15.8567 · Cited by 103 · see citing works
Encoding methods for combinatorial chemistry
Czarnik, A. W. (1997) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(97)80109-3 · Cited by 101 · see citing works
Uversky, V. N., Protasova, N. Y., Rogov, V. V., Vassilenko, K. S., Gudkov, A. T., & Kutyshenko, V. P. (1996) · Protein Science · doi:10.1002/pro.5560050910 · Cited by 77 · see citing works
Pseudostellarins D - F, new tyrosinase inhibitory cyclic peptides from Pseudostellaria heterophylla
Morita, H., Kayashita, T., Kobata, H., Gonda, A., Takeya, K., & Itokawa, H. (1994) · Tetrahedron · doi:10.1016/s0040-4020(01)89612-5 · Cited by 76 · see citing works
A fully active variant of dihydrofolate reductase with a circularly permuted sequence
Buchwalder, A., Szadkowski, H., & Kirschner, K. (1992) · Biochemistry · doi:10.1021/bi00121a006 · Cited by 75 · see citing works
Transdominant genetic analysis of a growth control pathway
Caponigro, G., Abedi, M. R., Hurlburt, A. P., Maxfield, A. B., Judd, W., & Kamb, A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7508 · Cited by 74 · see citing works
Melanin Production in Escherichia coli from a Cloned Tyrosinase Gene
della-Cioppa, G., Garger, S. J., Sverlow, G. G., Turpen, T. H., & Grill, L. K. (1990) · Nature Biotechnology · doi:10.1038/nbt0790-634 · Cited by 64 · see citing works
An arabinose-inducible expression vector, pAR3, compatible with ColE1-derived plasmids
Pérez‐Pérez, J., & Gutiérrez, J. (1995) · Gene · doi:10.1016/0378-1119(95)00127-r · Cited by 63 · see citing works
Miller, G. P., & Benkovic, S. J. (1998) · Biochemistry · doi:10.1021/bi972922t · Cited by 57 · see citing works
Self-citationSatoh, T. K., Li, S., Friedman, T. M., Wiaderkiewicz, R., Korngold, R., & Huang, Z. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1045 · Cited by 53 · see citing works
Iwakura, M., & Nakamura, T. (1998) · Protein Engineering Design and Selection · doi:10.1093/protein/11.8.707 · Cited by 49 · see citing works
Inhibition of Translation and Cell Growth by Minigene Expression
Tenson, T., Herrera, J. V., Kloss, P., Guarneros, G., & Mankin, A. S. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.5.1617-1622.1999 · Cited by 46 · see citing works
Synthesis of Peptides as Cloned Ubiquitin Extensions
Yoo, Y., Rote, K. V., & RECHSTEINER, M. C. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)71461-0 · Cited by 39 · see citing works
[23] Laser desorption mass spectrometry
Moore, W. T. (1997) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(97)89062-3 · Cited by 34 · see citing works
Genetic selection of short peptides that support protein oligomerization in vivo
Zhang, Z., Murphy, A., Hu, J. C., & Kodadek, T. J. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80188-2 · Cited by 25 · see citing works
Iwakura, M., & Honda, S. (1996) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a021257 · Cited by 24 · see citing works
[25] Using the lac repressor system to identify interacting proteins
Stricker, N. L., Schatz, P. J., & Li, M. (1999) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(99)03027-x · Cited by 5 · see citing works
Flagged first, then by citations
2 of the 40 references couldn’t be matched to a known paper.
Research works printed but not linked: 9
- Caponigro, G., Abedi, M. R., Hurlburt, A. P., Maxfield, A., Judd, W. & Kamb, A. (1998) Proc. Natl. Acad. Sci. USA 95, 7508-7513.
- Geyer, C. R., Colman-Lerner, A. & Brent, R. (1999) Proc. Natl. Acad. Sci. USA 96, 8567-8572.
- Davidson, A. R. & Sauer, R. T. (1994) Proc. Natl. Acad. Sci. USA 91, 2146-2150.
- McDaniel, R., Thamchaipenet, A., Gustafsson, C., Fu, H., Betlach, M., Betlach, M. & Ashley, G. (1999) Proc. Natl. Acad. Sci. USA 96, 1846-1851.
- Wu, H., Hu, Z. & Liu, X. Q. (1998) Proc. Natl. Acad. Sci. USA 95, 9226-9231.
- Ostermeier, M., Nixon, A. E., Shim, J. H. & Benkovic, S. J. (1999) Proc. Natl. Acad. Sci. USA 96, 3562-3567.
- Karimova, G., Pidoux, J., Ullmann, A. & Ladant, D. (1998) Proc. Natl. Acad. Sci. USA 95, 5752-5756.
- Xu, Y., Piston, D. W. & Johnson, C. H. (1999) Proc. Natl. Acad. Sci. USA 96, 151-156.
- Rossi, F., Charlton, C. A. & Blau, H. M. (1997) Proc. Natl. Acad. Sci. USA 94, 8405-8410.
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Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality
Sletten, E. M., & Bertozzi, C. R. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200900942 · Cited by 3,165 · see citing works
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Muir, T. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161900 · Cited by 692 · see citing works
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Björklund, M., & Koivunen, E. (2005) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2005.03.001 · Cited by 663 · see citing works
Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome
Neumann, H., Wang, K., Davis, L., Garcia-Alai, M., & Chin, J. W. (2010) · Nature · doi:10.1038/nature08817 · Cited by 622 · see citing works
Understanding Cell Penetration of Cyclic Peptides
Dougherty, P. G., Sahni, A., & Pei, D. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00008 · Cited by 581 · see citing works
Bioorthogonale Chemie – oder: in einem Meer aus Funktionalität nach Selektivität fischen
Sletten, E. M., & Bertozzi, C. R. (2009) · Angewandte Chemie · doi:10.1002/ange.200900942 · Cited by 564 · see citing works
Jennings, C. V., West, J., Waine, C., Craik, D. J., & Anderson, M. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191366898 · Cited by 524 · 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
The cyclization of peptides and depsipeptides
Davies, J. S. (2003) · Journal of Peptide Science · doi:10.1002/psc.491 · Cited by 449 · see citing works
Inteins: nature's gift to protein chemists
Shah, N. H., & Muir, T. W. (2014) · Chem. Sci. · doi:10.1039/c3sc52951g · Cited by 404 · see citing works
Protein ligation: an enabling technology for the biophysical analysis of proteins
Muralidharan, V., & Muir, T. W. (2006) · Nature Methods · doi:10.1038/nmeth886 · Cited by 363 · see citing works
Cyclic Peptides as Therapeutic Agents and Biochemical Tools
Joo, S. H. (2012) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2012.20.1.019 · Cited by 359 · see citing works
Melanin synthesis in microorganisms--biotechnological and medical aspects.
Plonka, P. M., & Grabacka, M. (2006) · Acta Biochimica Polonica · doi:10.18388/abp.2006_3314 · Cited by 341 · see citing works
Late‐Stage Peptide Diversification by Position‐Selective C−H Activation
Wang, W., Lorion, M. M., Shah, J., Kapdi, A. R., & Ackermann, L. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201806250 · Cited by 337 · see citing works
RNA Display Methods for the Discovery of Bioactive Macrocycles
Huang, Y., Wiedmann, M. M., & Suga, H. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00430 · Cited by 309 · see citing works
Highly efficient protein trans ‐splicing by a naturally split DnaE intein from Nostoc punctiforme
Iwaï, H., Züger, S., Jin, J., & Tam, P. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.02.045 · Cited by 273 · see citing works
Wang, K., Sachdeva, A., Cox, D. J., Wilf, N. M., Lang, K., Wallace, S., Mehl, R. A., & Chin, J. W. (2014) · Nature Chemistry · doi:10.1038/nchem.1919 · Cited by 269 · see citing works
Zettler, J., Schütz, V., & Mootz, H. D. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.02.003 · Cited by 260 · see citing works
Circular proteins — no end in sight
Trabi, M., & Craik, D. J. (2002) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(02)02057-1 · Cited by 255 · see citing works
Felizmenio-Quimio, M. E., Daly, N. L., & Craik, D. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101666200 · Cited by 240 · see citing works
Sohrabi, C., Foster, A., & Tavassoli, A. (2020) · Nature Reviews Chemistry · doi:10.1038/s41570-019-0159-2 · Cited by 230 · see citing works
Self-Assembling Peptides and Their Application in the Treatment of Diseases
Lee, S., Trinh, T. H. T., Yoo, M., Shin, J., Lee, H., Kim, J., Hwang, E., Lim, Y., & Ryou, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20235850 · Cited by 226 · see citing works
Selection-Based Discovery of Druglike Macrocyclic Peptides
Passioura, T., Katoh, T., Goto, Y., & Suga, H. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060713-035456 · Cited by 221 · see citing works
Inteins: Structure, Function, and Evolution
Gogarten, J. P., Senejani, A. G., Zhaxybayeva, O., Olendzenski, L., & Hilario, E. (2002) · Annual Review of Microbiology · doi:10.1146/annurev.micro.56.012302.160741 · Cited by 215 · see citing works
Controlling Macromolecular Topology with Genetically Encoded SpyTag–SpyCatcher Chemistry
Zhang, W., Sun, F., Tirrell, D. A., & Arnold, F. H. (2013) · Journal of the American Chemical Society · doi:10.1021/ja4076452 · Cited by 211 · see citing works
Evans, T. C., Martin, D. D., Kolly, R., Panne, D., Sun, L., Ghosh, I., Chen, L., Benner, J., Liu, X., & Xu, M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.13.9091 · Cited by 188 · see citing works
Miranda, E., Nordgren, I. K., Male, A. L., Lawrence, C. E., Hoakwie, F., Cuda, F., Court, W., Fox, K. R., Townsend, P. A., Packham, G. K., et al. (2013) · Journal of the American Chemical Society · doi:10.1021/ja402993u · Cited by 185 · see citing works
Bicyclic Peptides as Next‐Generation Therapeutics
Rhodes, C. A., & Pei, D. (2017) · Chemistry - A European Journal · doi:10.1002/chem.201702117 · Cited by 181 · see citing works
Macrocycles as protein–protein interaction inhibitors
Dougherty, P. G., Qian, Z., & Pei, D. (2017) · Biochemical Journal · doi:10.1042/bcj20160619 · Cited by 179 · see citing works
Rolleston, H. D. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9780511693632.005 · Cited by 179 · see citing works
SpyTag/SpyCatcher Cyclization Confers Resilience to Boiling on a Mesophilic Enzyme
Schoene, C., Fierer, J. O., Bennett, S., & Howarth, M. R. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201402519 · Cited by 177 · see citing works
Butelase 1: A Versatile Ligase for Peptide and Protein Macrocyclization
Nguyen, G. K. T., Kam, A., Loo, S., Jansson, A. E., Pan, L. X., & Tam, J. P. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b11014 · Cited by 177 · see citing works
Split-intein mediated circular ligation used in the synthesis of cyclic peptide libraries in E. coli
Tavassoli, A., & Benkovic, S. J. (2007) · Nature Protocols · doi:10.1038/nprot.2007.152 · Cited by 171 · see citing works
Self-citationBiological Applications of Protein Splicing
Vila‐Perelló, M., & Muir, T. W. (2010) · Cell · doi:10.1016/j.cell.2010.09.031 · Cited by 162 · see citing works
A Straight Path to Circular Proteins
Antos, J. M., Popp, M. W., Ernst, R., Chew, G.-L., Spooner, E., & Ploegh, H. L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m901752200 · Cited by 160 · see citing works
David, R., Richter, M., & Beck‐Sickinger, A. G. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2004.03978.x · Cited by 152 · see citing works
PROTEIN-SPLICING INTEIN: Genetic Mobility, Origin, and Evolution
Liu, X. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.61 · Cited by 149 · see citing works
Iwaï, H., Lingel, A., & Plückthun, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011639200 · Cited by 148 · see citing works
Tse, B. N., Snyder, T. M., Shen, Y., & Liu, D. R. (2008) · Journal of the American Chemical Society · doi:10.1021/ja805649f · Cited by 147 · see citing works
Diverse backbone-cyclized peptides via codon reprogramming
Kawakami, T., Ohta, A., Ohuchi, M., Ashigai, H., Murakami, H., & Suga, H. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.259 · Cited by 142 · see citing works
Lee, J., McIntosh, J. A., Hathaway, B. J., & Schmidt, E. W. (2009) · Journal of the American Chemical Society · doi:10.1021/ja8092168 · Cited by 140 · see citing works
Novel peptide therapeutics for treatment of infections
Oyston, P. C. F., Fox, M. A., Richards, S. J., & Clark, G. C. (2009) · Journal of Medical Microbiology · doi:10.1099/jmm.0.011122-0 · Cited by 138 · see citing works
Split Inteins as Versatile Tools for Protein Semisynthesis
Mootz, H. D. (2009) · ChemBioChem · doi:10.1002/cbic.200900370 · Cited by 140 · see citing works
Intein Applications: From Protein Purification and Labeling to Metabolic Control Methods
Wood, D. W., & Camarero, J. A. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r114.552653 · Cited by 139 · see citing works
SICLOPPS cyclic peptide libraries in drug discovery
Tavassoli, A. (2017) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2017.02.016 · Cited by 139 · see citing works
Targeting intracellular protein–protein interactions with cell-permeable cyclic peptides
Qian, Z., Dougherty, P. G., & Pei, D. (2017) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2017.03.011 · Cited by 136 · see citing works
Ding, Y., Xu, M., Ghosh, I., Chen, X., Ferrandon, S., Lesage, G., & Rao, Z. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306197200 · Cited by 139 · see citing works
Rapid selection of cyclic peptides that reduce α-synuclein toxicity in yeast and animal models
Kritzer, J. A., Hamamichi, S., McCaffery, J. M., Santagata, S., Naumann, T. A., Caldwell, K. A., Caldwell, G. A., & Lindquist, S. L. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.193 · Cited by 138 · see citing works
Disulfide-rich macrocyclic peptides as templates in drug design
Northfield, S. E., Wang, C. K. L., Schroeder, C. I., Durek, T., Kan, M., Swedberg, J. E., & Craik, D. J. (2014) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2014.03.011 · Cited by 135 · see citing works
Intein-Mediated Ligation and Cyclization of Expressed Proteins
Xu, M., & Evans, T. C. (2001) · Methods · doi:10.1006/meth.2001.1187 · Cited by 137 · see citing works
Approaches for peptide and protein cyclisation
Hayes, H. C., Luk, L. Y. P., & Tsai, Y. (2021) · Organic & Biomolecular Chemistry · doi:10.1039/d1ob00411e · Cited by 140 · see citing works
Zhang, L., & Falla, T. J. (2009) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2009.05.013 · Cited by 134 · see citing works
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Stevens, A. J., Sekar, G., Shah, N. H., Mostafavi, A. Z., Cowburn, D., & Muir, T. W. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1701083114 · Cited by 130 · see citing works
Züger, S., & Iwaï, H. (2005) · Nature Biotechnology · doi:10.1038/nbt1097 · Cited by 129 · see citing works
Cell-Permeable Bicyclic Peptide Inhibitors against Intracellular Proteins
Lian, W., Jiang, B., Qian, Z., & Pei, D. (2014) · Journal of the American Chemical Society · doi:10.1021/ja503710n · Cited by 128 · see citing works
Evolution of cyclic peptide protease inhibitors
Young, T. S., Young, D. D., Ahmad, I., Louis, J. M., Benkovic, S. J., & Schultz, P. G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108045108 · Cited by 128 · see citing works
Self-citationBiosynthesis of the Cyclotide Kalata B1 by Using Protein Splicing
Kimura, R. H., Tran, A., & Camarero, J. A. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200503882 · Cited by 120 · see citing works
Inteins, valuable genetic elements in molecular biology and biotechnology
Elleuche, S., & Pöggeler, S. (2010) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-010-2628-x · Cited by 118 · see citing works
Converting peptides into drugs targeting intracellular protein–protein interactions
Philippe, G. J.-B., Craik, D. J., & Henriques, S. T. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.01.022 · Cited by 115 · see citing works
Siebold, C., Flükiger, K., Beutler, R., & Erni, B. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02705-3 · Cited by 116 · see citing works
A systematic method for identifying small-molecule modulators of protein–protein interactions
Horswill, A. R., Savinov, S. N., & Benkovic, S. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406999101 · Cited by 110 · see citing works
Self-citationCyclic Peptides: Promising Scaffolds for Biopharmaceuticals
Gang, D., Kim, D.-W., & Park, H.-S. (2018) · Genes · doi:10.3390/genes9110557 · Cited by 103 · see citing works
Cyclic Luciferase for Real‐Time Sensing of Caspase‐3 Activities in Living Mammals
Kanno, A., Yamanaka, Y., Hirano, H., Umezawa, Y., & Ozawa, T. (2007) · Angewandte Chemie International Edition · doi:10.1002/anie.200700538 · Cited by 104 · see citing works
Sun, P., Ye, S., Ferrandon, S., Evans, T. C., Xu, M., & Rao, Z. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.09.039 · Cited by 103 · see citing works
Structural requirements for the biosynthesis of backbone cyclic peptide libraries
Scott, C. P., Abel‐Santos, E., Jones, A. D., & Benkovic, S. J. (2001) · Chemistry & Biology · doi:10.1016/s1074-5521(01)00052-7 · Cited by 101 · see citing works
Self-citationAppleby‐Tagoe, J. H., Thiel, I. V., Wang, Y., Wang, Y., Mootz, H. D., & Liu, X. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.277350 · Cited by 101 · see citing works
Rescuing a destabilized protein fold through backbone cyclization
Camarero, J. A., Fushman, D., Sato, S., Giriat, I., Cowburn, D., Raleigh, D. P., & Muir, T. W. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4631 · Cited by 99 · see citing works
Recent advances in in vivo applications of intein-mediated protein splicing
Topilina, N. I., & Mills, K. V. (2014) · Mobile DNA · doi:10.1186/1759-8753-5-5 · Cited by 97 · see citing works
Kinsella, T., Ohashi, C., Harder, A., Yam, G. C., Li, W.-Q., Peelle, B. R., Pali, E. S., Bennett, M., Molineaux, S., Anderson, D., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206162200 · Cited by 92 · see citing works
An alternative protein splicing mechanism for inteins lacking an N‐terminal nucleophile
Southworth, M. W., Benner, J., & Perler, F. B. (2000) · The EMBO Journal · doi:10.1093/emboj/19.18.5019 · Cited by 95 · see citing works
AS-48 bacteriocin: close to perfection
Sánchez‐Hidalgo, M., Montalbán‐López, M., Cebrián, R., Valdivia, E., Martínez‐Bueno, M., & Maqueda, M. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0724-4 · Cited by 93 · see citing works
Assessing the Combinatorial Potential of the RiPP Cyanobactin tru Pathway
Ruffner, D. E., Schmidt, E. W., & Heemstra, J. R. J. (2014) · ACS Synthetic Biology · doi:10.1021/sb500267d · Cited by 92 · see citing works
Expanded Utility of the Native Chemical Ligation Reaction
Yeo, D. S.-Y., Srinivasan, R., Chen, G. Y. J., & Yao, S. Q. (2004) · Chemistry - A European Journal · doi:10.1002/chem.200400414 · Cited by 91 · see citing works
Protein trans -splicing and its use in structural biology: opportunities and limitations
Volkmann, G., & Iwaï, H. (2010) · Molecular BioSystems · doi:10.1039/c0mb00034e · Cited by 87 · see citing works
Birts, C. N., Nijjar, S. K., Mardle, C. A., Hoakwie, F., Duriez, P. J., Blaydes, J. P., & Tavassoli, A. (2013) · Chemical Science · doi:10.1039/c3sc50481f · Cited by 85 · 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
Zhang, H., Kacharmina, J. E., Miyashiro, K., Greene, M. I., & Eberwine, J. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.101124598 · Cited by 83 · see citing works
Modularity of RiPP Enzymes Enables Designed Synthesis of Decorated Peptides
Sardar, D., Lin, Z., & Schmidt, E. W. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2015.06.014 · Cited by 81 · see citing works
Oeemig, J. S., Aranko, A. S., Djupsjöbacka, J., Heinämäki, K., & Iwaï, H. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.03.058 · Cited by 82 · see citing works
Lead discovery and optimization strategies for peptide macrocycles
Bhat, A., Roberts, L. R., & Dwyer, J. J. (2014) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2014.07.083 · Cited by 78 · see citing works
Protein splicing and its applications
Perler, F. B., & Adam, E. (2000) · Current Opinion in Biotechnology · doi:10.1016/s0958-1669(00)00113-0 · Cited by 79 · see citing works
Peptid‐Diversifizierung durch positionsselektive C‐H‐Aktivierung im späten Synthesestadium
Wang, W., Lorion, M. M., Shah, J., Kapdi, A. R., & Ackermann, L. (2018) · Angewandte Chemie · doi:10.1002/ange.201806250 · Cited by 78 · see citing works
Reversible Inhibition of Protein Splicing by Zinc Ion
Mills, K. V., & Paulus, H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011149200 · Cited by 78 · see citing works
Semisynthesis of Biologically Active Glycoforms of the Human Cytokine Interleukin 6
Reif, A., Siebenhaar, S., Tröster, A., Schmälzlein, M., Lechner, C. C., Velisetty, P., Gottwald, K., Pöhner, C., Boos, I., Schubert, V., et al. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201407160 · Cited by 77 · see citing works
Williams, N. K., Prosselkov, P. V., Liepinsh, E., Line, I., Sharipo, A., Littler, D. R., Curmi, P. M. G., Otting, G., & Dixon, N. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110303200 · Cited by 77 · see citing works
Nature-inspired protein ligation and its applications
Pihl, R., Zheng, Q., & David, Y. (2023) · Nature Reviews Chemistry · doi:10.1038/s41570-023-00468-z · Cited by 76 · see citing works
Biological Synthesis of Circular Polypeptides
Aboye, T. L., & Camarero, J. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.305508 · Cited by 76 · see citing works
Peptides Come Round: Using SICLOPPS Libraries for Early Stage Drug Discovery
Lennard, K. R., & Tavassoli, A. (2014) · Chemistry - A European Journal · doi:10.1002/chem.201403117 · Cited by 75 · see citing works
Chemical Topology and Complexity of Protein Architectures
Wang, X.-W., & Zhang, W. (2018) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2018.07.001 · Cited by 72 · see citing works
Choi, J. J., Nam, K. H., Min, B., Kim, S., Söll, D. G., & Kwon, S. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.12.036 · Cited by 70 · see citing works
Protein Splicing Mechanisms and Applications
Perler, F. B. (2005) · IUBMB Life · doi:10.1080/15216540500163343 · Cited by 70 · see citing works
Busche, A. E. L., Aranko, A. S., Talebzadeh‐Farooji, M., Bernhard, F., Dötsch, V., & Iwaï, H. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200901488 · Cited by 69 · see citing works
Characterization of the macrocyclase involved in the biosynthesis of RiPP cyclic peptides in plants
Chekan, J. R., Estrada, P., Covello, P. S., & Nair, S. K. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620499114 · Cited by 69 · see citing works
SYNBIP: synthetic binding proteins for research, diagnosis and therapy
Wang, X., Li, F., Qiu, W., Xu, B., Li, Y., Lian, X., Yu, H., Zhang, Z., Wang, J., Li, Z., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab926 · Cited by 69 · see citing works
Spurr, I. B., Birts, C. N., Cuda, F., Benkovic, S. J., Blaydes, J. P., & Tavassoli, A. (2012) · ChemBioChem · doi:10.1002/cbic.201200279 · Cited by 68 · see citing works
Self-citationSchoene, C., Bennett, S., & Howarth, M. R. (2016) · Scientific Reports · doi:10.1038/srep21151 · Cited by 67 · see citing works
Ribosomal Synthesis of Backbone-Cyclic Peptides Compatible with In Vitro Display
Takatsuji, R., Shinbara, K., Katoh, T., Goto, Y., Passioura, T., Yajima, R., Komatsu, Y., & Suga, H. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b05327 · Cited by 67 · see citing works
Protein semi-synthesis: New proteins for functional and structural studies
Durek, T., & Becker, C. F. W. (2005) · Biomolecular Engineering · doi:10.1016/j.bioeng.2005.07.004 · Cited by 66 · see citing works
Protein splicing mechanisms and applications
Perler, F. B. (2006) · IUBMB Life · doi:10.1080/15216540500531739 · 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
- Authors
- Scott, C. P., Abel-Santos, E., Wall, M., Wahnon, D. C., & Benkovic, S. J.
- Affiliations
- Pennsylvania State University (US)
- Department of Chemistry, Pennsylvania State University, University Park, PA 16802-6300
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-11-23
- Volume
- 96
- Issue
- 24
- Pages
- 13638-13643
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC24117
- OpenAlex
- W2152458717
- Cited by
- 402
- References
- 40
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 13 · 2023: 15 · 2022: 13 · 2021: 15 · 2020: 13 · 2019: 9 · 2018: 15 · 2017: 24 · 2016: 14 · 2015: 12 · 2014: 30 · 2013: 19 · 2012: 13
- FWCI
- 4.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- Pennsylvania State University
- National Institutes of Health
- National Institute of General Medical Sciences (GM19891-01, F32GM019891)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- split intein, cyclic peptides, dihydrofolate reductase, tyrosinase inhibitors, melanogenesis inhibition, Streptomyces antibioticus, Synechocystis sp. PCC 6803, thermal stability
- MeSH terms
- Bacterial Proteins, Genetic Engineering, Peptides, Cyclic, Tetrahydrofolate Dehydrogenase, Monophenol Monooxygenase
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