1 research outputs found
Caged Molecular Glues as Photoactivatable Tags for Nuclear Translocation of Guests in Living Cells
We
developed dendritic caged molecular glues (<sup>Caged</sup>Glue-R)
as tags for nucleus-targeted drug delivery, whose multiple guanidinium
ion (Gu<sup>+</sup>) pendants are protected by an anionic photocleavable
unit (butyrate-substituted nitroveratryloxycarbonyl; <sup>BA</sup>NVOC). Negatively charged <sup>Caged</sup>Glue-R hardly binds to
anionic biomolecules because of their electrostatic repulsion. However,
upon exposure of <sup>Caged</sup>Glue-R to UV light or near-infrared
(NIR) light, the <sup>BA</sup>NVOC groups of <sup>Caged</sup>Glue-R
are rapidly detached to yield an uncaged molecular glue (<sup>Uncaged</sup>Glue-R) that carries multiple Gu<sup>+</sup> pendants. Because Gu<sup>+</sup> forms a salt bridge with PO<sub>4</sub><sup>–</sup>, <sup>Uncaged</sup>Glue-R tightly adheres to anionic biomolecules
such as DNA and phospholipids in cell membranes by a multivalent salt-bridge
formation. When tagged with <sup>Caged</sup>Glue-R, guests can be
taken up into living cells via endocytosis and hide in endosomes.
However, when the <sup>Caged</sup>Glue-R tag is photochemically uncaged
to form <sup>Uncaged</sup>Glue-R, the guests escape from the endosome
and migrate into the cytoplasm followed by the cell nucleus. We demonstrated
that quantum dots (QDs) tagged with <sup>Caged</sup>Glue-R can be
delivered efficiently to cell nuclei eventually by irradiation with
light