De novo peptide grafting to a self-assembling nanocapsule yields a hepatocyte growth factor receptor agonist
Summary: Lasso-grafting (LG) technology is a method for generating de novo biologics (neobiologics) by genetically implanting macrocyclic peptide pharmacophores, which are selected in vitro against a protein of interest, into loops of arbitrary protein scaffolds. In this study, we have generated a n...
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Elsevier
2021
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oai:doaj.org-article:f66388c0f64b4cedba1f72a4ac812d782021-11-20T05:09:40ZDe novo peptide grafting to a self-assembling nanocapsule yields a hepatocyte growth factor receptor agonist2589-004210.1016/j.isci.2021.103302https://doaj.org/article/f66388c0f64b4cedba1f72a4ac812d782021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012712https://doaj.org/toc/2589-0042Summary: Lasso-grafting (LG) technology is a method for generating de novo biologics (neobiologics) by genetically implanting macrocyclic peptide pharmacophores, which are selected in vitro against a protein of interest, into loops of arbitrary protein scaffolds. In this study, we have generated a neo-capsid that potently binds the hepatocyte growth factor receptor MET by LG of anti-MET peptide pharmacophores into a circularly permuted variant of Aquifex aeolicus lumazine synthase (AaLS), a self-assembling protein nanocapsule. By virtue of displaying multiple-pharmacophores on its surface, the neo-capsid can induce dimerization (or multimerization) of MET, resulting in phosphorylation and endosomal internalization of the MET-capsid complex. This work demonstrates the potential of the LG technology as a synthetic biology approach for generating capsid-based neobiologics capable of activating signaling receptors.Yamato KomatsuNaohiro TerasakaKatsuya SakaiEmiko MiharaRisa WakabayashiKunio MatsumotoDonald HilvertJunichi TakagiHiroaki SugaElsevierarticlePeptidesBiotechnologySynthetic biologyScienceQENiScience, Vol 24, Iss 11, Pp 103302- (2021) |
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DOAJ |
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EN |
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Peptides Biotechnology Synthetic biology Science Q |
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Peptides Biotechnology Synthetic biology Science Q Yamato Komatsu Naohiro Terasaka Katsuya Sakai Emiko Mihara Risa Wakabayashi Kunio Matsumoto Donald Hilvert Junichi Takagi Hiroaki Suga De novo peptide grafting to a self-assembling nanocapsule yields a hepatocyte growth factor receptor agonist |
| description |
Summary: Lasso-grafting (LG) technology is a method for generating de novo biologics (neobiologics) by genetically implanting macrocyclic peptide pharmacophores, which are selected in vitro against a protein of interest, into loops of arbitrary protein scaffolds. In this study, we have generated a neo-capsid that potently binds the hepatocyte growth factor receptor MET by LG of anti-MET peptide pharmacophores into a circularly permuted variant of Aquifex aeolicus lumazine synthase (AaLS), a self-assembling protein nanocapsule. By virtue of displaying multiple-pharmacophores on its surface, the neo-capsid can induce dimerization (or multimerization) of MET, resulting in phosphorylation and endosomal internalization of the MET-capsid complex. This work demonstrates the potential of the LG technology as a synthetic biology approach for generating capsid-based neobiologics capable of activating signaling receptors. |
| format |
article |
| author |
Yamato Komatsu Naohiro Terasaka Katsuya Sakai Emiko Mihara Risa Wakabayashi Kunio Matsumoto Donald Hilvert Junichi Takagi Hiroaki Suga |
| author_facet |
Yamato Komatsu Naohiro Terasaka Katsuya Sakai Emiko Mihara Risa Wakabayashi Kunio Matsumoto Donald Hilvert Junichi Takagi Hiroaki Suga |
| author_sort |
Yamato Komatsu |
| title |
De novo peptide grafting to a self-assembling nanocapsule yields a hepatocyte growth factor receptor agonist |
| title_short |
De novo peptide grafting to a self-assembling nanocapsule yields a hepatocyte growth factor receptor agonist |
| title_full |
De novo peptide grafting to a self-assembling nanocapsule yields a hepatocyte growth factor receptor agonist |
| title_fullStr |
De novo peptide grafting to a self-assembling nanocapsule yields a hepatocyte growth factor receptor agonist |
| title_full_unstemmed |
De novo peptide grafting to a self-assembling nanocapsule yields a hepatocyte growth factor receptor agonist |
| title_sort |
de novo peptide grafting to a self-assembling nanocapsule yields a hepatocyte growth factor receptor agonist |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/f66388c0f64b4cedba1f72a4ac812d78 |
| work_keys_str_mv |
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