Sense-and-Release Logic-Gated Molecular Network Responding to Dimeric Cell Surface Proteins.

Angerani S; Winssinger N

doi:10.1021/jacs.0c04469

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Journal article

Sense-and-Release Logic-Gated Molecular Network Responding to Dimeric Cell Surface Proteins.

Angerani S Department of Organic Chemistry, NCCR Chemical Biology, Faculty of Science, University of Geneva, 30 quai Ernest Ansermet, 1205 Geneva, Switzerland.
Winssinger N Department of Organic Chemistry, NCCR Chemical Biology, Faculty of Science, University of Geneva, 30 quai Ernest Ansermet, 1205 Geneva, Switzerland.

2020-06-17

Published in:

Journal of the American Chemical Society. - 2020

English Dimeric proteins are prominent in biology, and receptor dimerization (homo- or heterodimerization) is central to signal transduction. Herein, we report a network that responds to a membrane-associated dimeric protein with the uncaging of a powerful cytotoxic. The network is based on two ligands functionalized with peptide nucleic acids (PNAs) (templating strand and catalyst-functionalized strand, respectively) and a substrate with the caged cytotoxic (monomethyl auristatin E: MMAE; a high-affinity tubulin ligand). In the presence of the dimeric protein, the network yields a cooperative supramolecular assembly with a hybridization architecture that enhances the templated reaction and enables the uncaging of a substrate. The network was tested on cells that express a cancer biomarker, carbonic anhydrase IX, in response to hypoxia. The output of the network correlates with the expression of carbonic anhydrase IX, and this biomarker was harnessed to uncage a potent cytotoxic agent.

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