De novo design of growth factor inhibiting proteins

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MAKSYMENKO, Kateryna, Julia SKOKOWA, Andrei N. LUPAS, Narges AGHAALLAEI, Patrick MÜLLER, Mohammad ELGAMACY, 2022. De novo design of growth factor inhibiting proteins. In: Klinische Pädiatrie. Georg Thieme Verlag. 234(03), pp. 185-186. ISSN 0300-8630. eISSN 1439-3824. Available under: doi: 10.1055/s-0042-1748729

@article{Maksymenko2022desig-58476, title={De novo design of growth factor inhibiting proteins}, year={2022}, doi={10.1055/s-0042-1748729}, number={03}, volume={234}, issn={0300-8630}, journal={Klinische Pädiatrie}, pages={185--186}, author={Maksymenko, Kateryna and Skokowa, Julia and Lupas, Andrei N. and Aghaallaei, Narges and Müller, Patrick and ElGamacy, Mohammad} }

<rdf:RDF xmlns:dcterms="" xmlns:dc="" xmlns:rdf="" xmlns:bibo="" xmlns:dspace="" xmlns:foaf="" xmlns:void="" xmlns:xsd="" > <rdf:Description rdf:about=""> <dcterms:available rdf:datatype="">2022-09-01T13:19:44Z</dcterms:available> <dc:creator>Müller, Patrick</dc:creator> <dc:contributor>Maksymenko, Kateryna</dc:contributor> <dc:creator>Skokowa, Julia</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:language>eng</dc:language> <dc:rights>terms-of-use</dc:rights> <dcterms:isPartOf rdf:resource=""/> <dc:contributor>Skokowa, Julia</dc:contributor> <dc:contributor>Aghaallaei, Narges</dc:contributor> <dcterms:abstract xml:lang="eng">Growth factors are signaling molecules coordinating the complex functionality of multicellular organisms during development and homeostasis. Since aberrant expression of growth factors can cause diverse disorders, growth factors and their receptors are central targets for therapeutic modulation. Here, we present two different strategies of computational protein design to obtain inhibitors against growth factors which contribute to tumor progression. Adopting a re-engineering approach, we designed inhibitors of epidermal growth factor (EGF) using a single domain of EGF receptor as a template. Experimental evaluation of two designed candidates revealed that both of them bind EGF with nanomolar affinities and inhibit EGF-induced proliferation of epidermoid carcinoma cell line. Using a de novo design strategy, we designed inhibitors of vascular endothelial growth factor (VEGF). The best designs showed the ability to inhibit proliferation of VEGF-dependent cells in vitro and in zebrafish assays. Thus, our results demonstrate the feasibility of computational protein design approaches to create therapeutic leads in a time- and cost-effective manner.</dcterms:abstract> <dc:contributor>Müller, Patrick</dc:contributor> <dc:creator>Maksymenko, Kateryna</dc:creator> <dc:creator>ElGamacy, Mohammad</dc:creator> <dc:date rdf:datatype="">2022-09-01T13:19:44Z</dc:date> <dcterms:title>De novo design of growth factor inhibiting proteins</dcterms:title> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <bibo:uri rdf:resource=""/> <dc:creator>Aghaallaei, Narges</dc:creator> <dcterms:issued>2022</dcterms:issued> <dspace:isPartOfCollection rdf:resource=""/> <dc:contributor>Lupas, Andrei N.</dc:contributor> <dc:creator>Lupas, Andrei N.</dc:creator> <dcterms:rights rdf:resource=""/> <dc:contributor>ElGamacy, Mohammad</dc:contributor> </rdf:Description> </rdf:RDF>

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