Skip to main content
Log in

Engineering von intrazellulären Modulatoren

  • Wissenschaft · Methoden
  • Protein-Protein-Interaktionen
  • Published:
BIOspektrum Aims and scope

Abstract

The engineering of affinity reagents has become a standard technology in modern drug development efforts. High-throughput screening of recombinant protein libraries has yielded numerous affinity reagents that are used in diagnostic or therapeutic applications. In our approach, we engineer intracellular affinity reagents by enhancing pre-existing intermolecular contacts to target functional epitopes in proteins. The designed affinity reagents allow a fast and specific interrogation of druggable sites in therapeutic relevant proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Literatur

  1. Cohen P, Tcherpakov M (2010) Will the ubiquitin system furnish as many drug targets as protein kinases? Cell 143:686–693

    Article  CAS  PubMed  Google Scholar 

  2. Rolland T, Tasan M, Charloteaux B, et al. (2014) A proteome-scale map of the human interactome network. Cell 159:1212–1226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Argos P (1988) An investigation of protein subunit and domain interfaces. Protein Eng 2:101–113

    Article  CAS  PubMed  Google Scholar 

  4. Vajda S, Guarnieri F (2006) Characterization of protein-ligand interaction sites using experimental and computational methods. Curr Opin Drug Discov Devel 9:354–362

    CAS  PubMed  Google Scholar 

  5. Tomlinson IM (2004) Next-generation protein drugs. Nat Biotechnol 22:521–522

    Article  CAS  PubMed  Google Scholar 

  6. Koide A, Abbatiello S, Rothgery L, et al. (2002) Probing protein conformational changes in living cells by using designer binding proteins: application to the estrogen receptor. Proc Natl Acad Sci USA 99:1253–1258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Binz HK, Amstutz P, Kohl A, et al. (2004) High-affinity binders selected from designed ankyrin repeat protein libraries. Nat Biotechnol 22:575–582

    Article  CAS  PubMed  Google Scholar 

  8. Ernst A, Avvakumov G, Tong J, et al. (2013) A strategy for modulation of enzymes in the ubiquitin system. Science 339:590–595

    Article  CAS  PubMed  Google Scholar 

  9. Liu F, Walters KJ (2010) Multitasking with ubiquitin through multivalent interactions. Trends Biochem Sci 35:352–360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhang D, Raasi S, Fushman D (2008) Affinity makes the difference: nonselective interaction of the UBA domain of Ubiquilin-1 with monomeric ubiquitin and polyubiquitin chains. J Mol Biol 377:162–180

    Article  CAS  PubMed  Google Scholar 

  11. Wiechmann S, Gartner A, Kniss A, et al. (2017) Site-specific inhibition of the SUMO-conjugating enzyme Ubc9 selectively impairs SUMO chain formation. J Biol Chem, DOI:10.1074/ibc.M117.794255

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andreas Ernst.

Additional information

Svenja Wiechmann 20072013 Biologiestudium an der TU Darmstadt. Seit 2013 Doktorandin im Institut für Biochemie II, Goethe Universität Frankfurt a. M.

Andreas Ernst 19932000 Chemiestudium an der TU Darmstadt. 20002006 Promotion an der Universität Zürich, Schweiz, im Labor von Prof. Dr. Andreas Plückthun. 20072008 Postdoc in San Francisco, CA, USA, im Department Proteinengineering bei Genentech in der Arbeitsgruppe von Dr. S. Sidhu. 2008 Umzug mit Dr. S. Sidhu an die Universität Toronto, Kanada, an das Centre for Cellular and Biomolecular Research. Seit 2013 Gruppenleiter im Institut für Biochemie II, Goethe Universität Frankfurt a. M. und seit 2015 in Nebentätigkeit als Gruppenleiter am Fraunhofer-Institut für Molekular biologie und Angewandte Ökologie, Projektgruppe Translationale Medizin und Pharmakologie, Frankfurt a. M.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wiechmann, S., Ernst, A. Engineering von intrazellulären Modulatoren. Biospektrum 23, 769–771 (2017). https://doi.org/10.1007/s12268-017-0870-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12268-017-0870-9

Navigation