We developed a dendritic molecular glue Glue-NBD that can serve universally to "turn on" protein-protein interactions (PPIs) spatiotemporally. Glue-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, Glue-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 Glue-NBD, lost the affinity toward its receptor c-Met. However, upon exposure of the Glue-NBD/HGF hybrid to light-emitting diode light (365 nm), the Glue-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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