One of the major goals of modern chemotherapy is to develop smart prodrugs and delivery systems that are activated selectively within cancer cells or in the tumor microenvironment. Towards this long-term goal, our group has been pursuing a supramolecular chemistry based approach to responsive molecules that bind and inhibit protein targets only upon being triggered by endogenous oligonucleotide inputs. This seminar will detail how supramolecular and nucleic acid chemistries can be combined to generate DNA small-molecule chimeras (DCs) that bind proteins in an input-responsive manner. Specifically, we will first describe DCs that that upon activation (or self-assembly) switch from low-affinity monodentate to high-affinity bidentate protein-binding states. With the goal of transitioning these stimuli-responsive DCs into complex biological environments and cells, we will also discuss (a) DCs that are triggered by cancer-associated microRNAs, and (b) DCs that are designed to function in the presence of denaturing and nuclease-induced degradation conditions.

Supramolecular methods to achieve input responsive protein-binders

251st National Meeting (2016)

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