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De novo design of growth factor inhibiting proteins

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2022

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Maksymenko, Kateryna
Skokowa, Julia
Lupas, Andrei N.
Aghaallaei, Narges
ElGamacy, Mohammad

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Klinische Pädiatrie. Georg Thieme Verlag. 2022, 234(03), pp. 185-186. ISSN 0300-8630. eISSN 1439-3824. Available under: doi: 10.1055/s-0042-1748729

Zusammenfassung

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.

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570 Biowissenschaften, Biologie

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ISO 690MAKSYMENKO, 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. 2022, 234(03), pp. 185-186. ISSN 0300-8630. eISSN 1439-3824. Available under: doi: 10.1055/s-0042-1748729
BibTex
@article{Maksymenko2022desig-58476,
  year={2022},
  doi={10.1055/s-0042-1748729},
  title={De novo design of growth factor inhibiting proteins},
  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}
}
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