We present the design and application of a new type of biosensor consisting of two primary components: 1) a small molecule with selectivity for the active state of the target protein, and 2) an environmentally sensitive and membrane permeant dye. The dye was optimized for photophysical properties and uniformity of intracellular distribution and was then conjugated to a chemically modified version of the small molecule in a position that would not interfere with normal binding interactions. The biosensor showed an activation state specific increase in fluorescence intensity upon target binding in vitro of more than tenfold. Subsequent live cell imaging studies showed unique localization of the biosensor signal relative to controls. Current work is focused on exploring the potential of the optimized dyes for in vivo protein labeling and on further application of the small molecule based biosensor approach to other targets of interest.

Building better biosensors with the tools of chemical biology

244th National Meeting (2012)

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