Design of novel granulopoietic proteins by topological rescaffolding

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HERNANDEZ ALVAREZ, Birte, Julia SKOKOWA, Murray COLES, Perihan MIR, Masoud NASRI, Kateryna MAKSYMENKO, Laura WEIDMANN, Katherine W. ROGERS, Patrick MÜLLER, Mohammad ELGAMACY, 2020. Design of novel granulopoietic proteins by topological rescaffolding. In: PLoS biology. Public Library of Science (PLoS). 18(12), e3000919. ISSN 1544-9173. eISSN 1545-7885. Available under: doi: 10.1371/journal.pbio.3000919

@article{HernandezAlvarez2020Desig-56465, title={Design of novel granulopoietic proteins by topological rescaffolding}, year={2020}, doi={10.1371/journal.pbio.3000919}, number={12}, volume={18}, issn={1544-9173}, journal={PLoS biology}, author={Hernandez Alvarez, Birte and Skokowa, Julia and Coles, Murray and Mir, Perihan and Nasri, Masoud and Maksymenko, Kateryna and Weidmann, Laura and Rogers, Katherine W. and Müller, Patrick and ElGamacy, Mohammad}, note={Article Number: e3000919} }

<rdf:RDF xmlns:dcterms="" xmlns:dc="" xmlns:rdf="" xmlns:bibo="" xmlns:dspace="" xmlns:foaf="" xmlns:void="" xmlns:xsd="" > <rdf:Description rdf:about=""> <dc:date rdf:datatype="">2022-02-09T11:30:48Z</dc:date> <dc:contributor>Müller, Patrick</dc:contributor> <dc:creator>Nasri, Masoud</dc:creator> <dc:creator>Mir, Perihan</dc:creator> <dc:contributor>Mir, Perihan</dc:contributor> <dc:creator>Maksymenko, Kateryna</dc:creator> <dc:rights>Attribution 4.0 International</dc:rights> <dspace:hasBitstream rdf:resource=""/> <dspace:isPartOfCollection rdf:resource=""/> <dcterms:available rdf:datatype="">2022-02-09T11:30:48Z</dcterms:available> <dcterms:rights rdf:resource=""/> <dc:creator>Weidmann, Laura</dc:creator> <dc:contributor>Nasri, Masoud</dc:contributor> <dc:creator>Müller, Patrick</dc:creator> <dcterms:hasPart rdf:resource=""/> <dcterms:title>Design of novel granulopoietic proteins by topological rescaffolding</dcterms:title> <dc:creator>Coles, Murray</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:creator>ElGamacy, Mohammad</dc:creator> <bibo:uri rdf:resource=""/> <dc:contributor>Weidmann, Laura</dc:contributor> <dc:contributor>Coles, Murray</dc:contributor> <dc:contributor>ElGamacy, Mohammad</dc:contributor> <dc:contributor>Hernandez Alvarez, Birte</dc:contributor> <dc:contributor>Skokowa, Julia</dc:contributor> <dcterms:isPartOf rdf:resource=""/> <dc:creator>Rogers, Katherine W.</dc:creator> <dc:creator>Skokowa, Julia</dc:creator> <dc:language>eng</dc:language> <dcterms:issued>2020</dcterms:issued> <dc:creator>Hernandez Alvarez, Birte</dc:creator> <dc:contributor>Maksymenko, Kateryna</dc:contributor> <dc:contributor>Rogers, Katherine W.</dc:contributor> <dcterms:abstract xml:lang="eng">Computational protein design is rapidly becoming more powerful, and improving the accuracy of computational methods would greatly streamline protein engineering by eliminating the need for empirical optimization in the laboratory. In this work, we set out to design novel granulopoietic agents using a rescaffolding strategy with the goal of achieving simpler and more stable proteins. All of the 4 experimentally tested designs were folded, monomeric, and stable, while the 2 determined structures agreed with the design models within less than 2.5 Å. Despite the lack of significant topological or sequence similarity to their natural granulopoietic counterpart, 2 designs bound to the granulocyte colony-stimulating factor (G-CSF) receptor and exhibited potent, but delayed, in vitro proliferative activity in a G-CSF-dependent cell line. Interestingly, the designs also induced proliferation and differentiation of primary human hematopoietic stem cells into mature granulocytes, highlighting the utility of our approach to develop highly active therapeutic leads purely based on computational design.</dcterms:abstract> </rdf:Description> </rdf:RDF>

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