Selective Cavitand-Mediated Endocytosis of Targeted Imaging Agents into Live Cells

Abstract

A water-soluble synthetic receptor molecule is capable of selective, controlled endocytosis of a specifically tagged target molecule in different types of living human cells. The presence of suitable choline-derived binding handles is essential for the molecular recognition and transport process, allowing selective guest transport and imaging of cancer cells.

Inhibition of histone binding by supramolecular hosts

“…Supramolecular agents that target artificially introduced bio-orthogonal structural motifs have made a substantial impact in chemical biology [34,35]; however, examples that work on biomolecules in their native cell environment remain exceedingly rare [36]. In the present study we show that the calixarene-based macrocycle hosts selectively disrupt binding of the CHD4 PHD2 finger to H3K9me3 while not affecting the interaction of this protein with H3K9me0.…”

Calixarene‐Mediated Liquid‐Membrane Transport of Choline Conjugates

“…[11] This body of work has encouraged us to apply these results to cellular systems; it has been shown that resorcinarene cavitands can promote the endocytosis of fluorescein, so long as a complementary choline handle is attached. [12] The observation that selective endocytosis is possible is quite remarkable – a non-covalent supramolecular host–guest assembly crosses a cell membrane!…”

Calixarene‐Mediated Liquid Membrane Transport of Choline Conjugates 2: Transport of Drug‐Choline Conjugates and Neurotransmitters

“…This strategy diverges from emulsification or covalent conjugate strategies yet is not so farfetched as to prohibit ultimate applications in cells. [11,25] We know that supramolecular receptors are compatible with cells and we can monitor their localization tendencies in giant unilamellar vesicles. [9] A final report on the behavior of guests in buffer as well as a comparison of trimethylammonium vs. ammonium vs. ammonium dicarboxylate species will be reported in due course.…”

“…[9] Our colleagues have demonstrated remarkable functions for these systems as surface bound receptors for protein sensing [10] and, most interestingly, as facilitators of endocytosis for guest molecules! [11] These properties have been developed under constraints of the host, as they are largely incompatible with pure water environments. We had hoped that resorcinarene cavitands would be a suitable prototype for transport.…”