Abstract
In this communication we present the peptide-guided assembly of complementary fragments of designed armadillo repeat proteins (dArmRPs) to create proteins that bind peptides not only with high affinity but also with good selectivity. We recently demonstrated that complementary N- and C-terminal fragments of dArmRPs form high-affinity complexes that resemble the structure of the full-length protein, and that these complexes bind their target peptides. We now demonstrate that dArmRPs can be split such that the fragments assemble only in the presence of a templating peptide, and that fragment mixtures enrich the combination with the highest affinity for this peptide. The enriched fragment combination discriminates single amino acid variations in the target peptide with high specificity. Our results suggest novel opportunities for the generation of new peptide binders by selection from dArmRP fragment mixtures.
Item Type: | Journal Article, refereed, further contribution |
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Communities & Collections: | 04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
07 Faculty of Science > Department of Chemistry |
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Dewey Decimal Classification: | 540 Chemistry |
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Scopus Subject Areas: | Physical Sciences > Catalysis
Physical Sciences > General Chemistry |
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Uncontrolled Keywords: | Library, , Armadillo, , Protein Fragment, , Peptide Binder |
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Language: | English |
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Date: | 2018 |
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Deposited On: | 16 Mar 2018 20:04 |
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Last Modified: | 18 Jan 2025 02:39 |
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Publisher: | Wiley-VCH Verlag |
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ISSN: | 1433-7851 |
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Funders: | Swiss National Science Foundation, Forschungskredit Uni Zürich |
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Additional Information: | For accepted manuscripts: This is the peer reviewed version of the following article: Michel, Erich; Plückthun, Andreas; Zerbe, Oliver (2018). Peptide-guided assembly of repeat protein fragments. Angewandte Chemie Internationale Edition:Epub ahead of print., which has been published in final form at https://doi.org/10.1002/anie.201713377. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-820227.html#terms). |
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OA Status: | Green |
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Publisher DOI: | https://doi.org/10.1002/anie.201713377 |
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PubMed ID: | 29480529 |
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Project Information: | - Funder: SNSF
- Grant ID:
- Project Title: Swiss National Science Foundation
- Funder:
- Grant ID:
- Project Title: Forschungskredit Uni Zürich
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