Molecular Glue that Spatiotemporally Turns on Protein-Protein Interactions.
J Am Chem Soc
; 141(20): 8035-8040, 2019 05 22.
Article
en En
| MEDLINE
| ID: mdl-30977371
ABSTRACT
We developed a dendritic molecular glue PCGlue-NBD that can serve universally to "turn on" protein-protein interactions (PPIs) spatiotemporally. PCGlue-NBD carrying multiple guanidinium ion (Gu+) pendants can adhere strongly to target proteins and cover their surfaces including the PPI interface regions, thereby suppressing PPIs with their receptor proteins. Upon irradiation with UV light, PCGlue-NBD on a target protein is photocleaved at butyrate-substituted nitroveratryloxycarbonyl linkages in the dendrimer framework, so that the multivalency for the adhesion is reduced. Consequently, the guest protein is liberated and becomes eligible for a PPI. We found that hepatocyte growth factor HGF, when mixed with PCGlue-NBD, lost the affinity toward its receptor c-Met. However, upon exposure of the PCGlue-NBD/HGF hybrid to light-emitting diode light (365 nm), the PCGlue-NBD molecules on HGF were photocleaved as described above, so that HGF was liberated and retrieved its intrinsic PPI affinity toward c-Met. The turn-on PPI, thus achieved for HGF and c-Met, leads to cell migration, which can be made spatiotemporally with a millimeter-scale resolution by pointwise irradiation with UV light.
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Base de datos:
MEDLINE
Asunto principal:
Unión Proteica
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Factor de Crecimiento de Hepatocito
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Proteínas Proto-Oncogénicas c-met
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Dendrímeros
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Guanidinas
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4-Cloro-7-nitrobenzofurazano
Límite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón