Ubiquitin is a versatile scaffold protein for the generation of molecules withde novo binding and advantageous drug‐like properties
In the search for effective therapeutic strategies, protein‐based biologicals are under intense development. While monoclonal antibodies represent the majority of these drugs, other innovative approaches are exploring the use of scaffold proteins for the creation of binding molecules with tailor‐mad...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1016/j.fob.2015.07.002 |
| _version_ | 1811178419373735936 |
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| author | Florian Job Florian Settele Susan Lorey Chris Rundfeldt Lars Baumann Annette G. Beck-Sickinger Ulrich Haupts Hauke Lilie Eva Bosse-Doenecke |
| author_facet | Florian Job Florian Settele Susan Lorey Chris Rundfeldt Lars Baumann Annette G. Beck-Sickinger Ulrich Haupts Hauke Lilie Eva Bosse-Doenecke |
| author_sort | Florian Job |
| collection | DOAJ |
| description | In the search for effective therapeutic strategies, protein‐based biologicals are under intense development. While monoclonal antibodies represent the majority of these drugs, other innovative approaches are exploring the use of scaffold proteins for the creation of binding molecules with tailor‐made properties. Ubiquitin is especially suited for this strategy due to several key characteristics. Ubiquitin is a natural serum protein, 100% conserved across the mammalian class and possesses high thermal, structural and proteolytic stability. Because of its small size and lack of posttranslational modifications, it can be easily produced inEscherichia coli. In this work we provide evidence that ubiquitin is safe as tested experimentallyin vivo. In contrast to previously published results, we show that, in our hands, ubiquitin does not act as a functional ligand of the chemokine receptor CXCR4. Cellular assays based on different signaling pathways of the receptor were conducted with the natural agonist SDF‐1 as a benchmark. In none of the assays could a response to ubiquitin treatment be elicited. Furthermore, intravenous application to mice at high concentrations did not induce any detectable effect on cytokine levels or hematological parameters. |
| first_indexed | 2024-04-11T06:18:00Z |
| format | Article |
| id | doaj.art-e7f8eece52da409e85bd005ae63a9579 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-11T06:18:00Z |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-e7f8eece52da409e85bd005ae63a95792022-12-22T04:40:59ZengWileyFEBS Open Bio2211-54632015-01-015157959310.1016/j.fob.2015.07.002Ubiquitin is a versatile scaffold protein for the generation of molecules withde novo binding and advantageous drug‐like propertiesFlorian Job0Florian Settele1Susan Lorey2Chris Rundfeldt3Lars Baumann4Annette G. Beck-Sickinger5Ulrich Haupts6Hauke Lilie7Eva Bosse-Doenecke8Institute for Biochemistry and Biotechnology/Technical Biochemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Straße 3, D-06120 Halle (Saale), GermanyScil Proteins GmbH, Heinrich-Damerow-Straße 1, D-06120 Halle (Saale), GermanyScil Proteins GmbH, Heinrich-Damerow-Straße 1, D-06120 Halle (Saale), GermanyScil Proteins GmbH, Heinrich-Damerow-Straße 1, D-06120 Halle (Saale), GermanyInstitute of Biochemistry, University of Leipzig, Brüderstraße 34, D-04103 Leipzig, GermanyInstitute of Biochemistry, University of Leipzig, Brüderstraße 34, D-04103 Leipzig, GermanyScil Proteins GmbH, Heinrich-Damerow-Straße 1, D-06120 Halle (Saale), GermanyInstitute for Biochemistry and Biotechnology/Technical Biochemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Straße 3, D-06120 Halle (Saale), GermanyScil Proteins GmbH, Heinrich-Damerow-Straße 1, D-06120 Halle (Saale), GermanyIn the search for effective therapeutic strategies, protein‐based biologicals are under intense development. While monoclonal antibodies represent the majority of these drugs, other innovative approaches are exploring the use of scaffold proteins for the creation of binding molecules with tailor‐made properties. Ubiquitin is especially suited for this strategy due to several key characteristics. Ubiquitin is a natural serum protein, 100% conserved across the mammalian class and possesses high thermal, structural and proteolytic stability. Because of its small size and lack of posttranslational modifications, it can be easily produced inEscherichia coli. In this work we provide evidence that ubiquitin is safe as tested experimentallyin vivo. In contrast to previously published results, we show that, in our hands, ubiquitin does not act as a functional ligand of the chemokine receptor CXCR4. Cellular assays based on different signaling pathways of the receptor were conducted with the natural agonist SDF‐1 as a benchmark. In none of the assays could a response to ubiquitin treatment be elicited. Furthermore, intravenous application to mice at high concentrations did not induce any detectable effect on cytokine levels or hematological parameters.https://doi.org/10.1016/j.fob.2015.07.002UbiquitinScaffoldCXCR4SDF-1G-protein coupled receptorBiodistribution |
| spellingShingle | Florian Job Florian Settele Susan Lorey Chris Rundfeldt Lars Baumann Annette G. Beck-Sickinger Ulrich Haupts Hauke Lilie Eva Bosse-Doenecke Ubiquitin is a versatile scaffold protein for the generation of molecules withde novo binding and advantageous drug‐like properties FEBS Open Bio Ubiquitin Scaffold CXCR4 SDF-1 G-protein coupled receptor Biodistribution |
| title | Ubiquitin is a versatile scaffold protein for the generation of molecules withde novo binding and advantageous drug‐like properties |
| title_full | Ubiquitin is a versatile scaffold protein for the generation of molecules withde novo binding and advantageous drug‐like properties |
| title_fullStr | Ubiquitin is a versatile scaffold protein for the generation of molecules withde novo binding and advantageous drug‐like properties |
| title_full_unstemmed | Ubiquitin is a versatile scaffold protein for the generation of molecules withde novo binding and advantageous drug‐like properties |
| title_short | Ubiquitin is a versatile scaffold protein for the generation of molecules withde novo binding and advantageous drug‐like properties |
| title_sort | ubiquitin is a versatile scaffold protein for the generation of molecules withde novo binding and advantageous drug like properties |
| topic | Ubiquitin Scaffold CXCR4 SDF-1 G-protein coupled receptor Biodistribution |
| url | https://doi.org/10.1016/j.fob.2015.07.002 |
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