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Multivalent Cucurbituril Dendrons for Cell Membrane Engineering with Supramolecular Receptors.

Brant D GatesJackson B VyletelLei ZouMatthew J Webber
Published in: Bioconjugate chemistry (2022)
The affinity possible from certain supramolecular motifs rivals that for some of the best-recognized interactions in biology. Cucurbit[7]uril (CB[7]) macrocycles, for example, are capable of achieving affinities in their binding to certain guests that rival that of biotin-avidin. Supramolecular host-guest recognition between CB[7] and certain guests has been demonstrated to spatially localize guest-linked agents to desired sites in vivo , offering opportunities to better exploit this affinity axis for applications in biomedicine. Herein, architectures of CB[7] are prepared from a polyamidoamine (PAMAM) dendrimer scaffold, installing a PEG-linked cholesterol anchor on the opposite end of the dendron to facilitate cell membrane integration. Cells are then modified with this dendritic CB[7] construct in vitro , demonstrating the ability to deliver a model guest-linked agent to the cell membrane. This approach to realize synthetic supramolecular "membrane receptors" may be leveraged in the future for in situ imaging or modulation of cell-based therapies or to facilitate a synthetic supramolecular recognition axis on the cell membrane.
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