Friday, November 6, 2009: 1:50 PM
Rio Grande (Camino Real Hotel)
Protein-binding agents that can be controlled by external or intrinsic stimuli have potential as more effective chemotherapeutics with attenuated adverse effects. The field of supramolecular chemistry is uniquely placed to contribute to the development of such agents by designing switchable molecules with multiple and selective molecular recognition modalities. In this presentation, we describe how the interplay between oligonucleotide (ODN) self-assembly can be used to modulate synthetic molecule-protein interactions. In particular, this work will focus on a responsive DNA-small molecule chimera (DC) 1 that binds to serine protease trypsin. DC 1 contains two synthetic protein-binding arms flanking a central ODN domain and undergoes structure-switching from a bidentate intramolecular quadruplex form to a monodentate duplex structure (and vice-versa) via addition of external ODN stimuli. Importantly, these distinct secondary structures of 1 lead to substantially different protein-binding abilities, with the bidentate conformation exhibiting a 20-fold enhancement (with a 0.8 μM dissociation constant, Kd) in trypsin-binding. Also discussed is an aptamer-small molecule chimera capable of protein sensing.