Photoactivatable fluorescent small molecules are powerful tools to study biological systems, due to their high spatial and temporal resolution and their ability to be precisely controlled by light.  Although many small molecule photoactivable probes are widely used, most of these probes generally undergo a change from an initial non-fluorescent state into a fluorescent state via photoisomerization, photo-uncaging, or photodecomposition.  To provide a better system for trafficking biomolecules, a clickable photoconvertable fluorophore that is emissive in both its pre- and post-activated state is developed. As photoactivation is driven by photoelectrocyclization and is orthogonal to clickable handle, our probe demonstrates a generally applicable toolkit for the conjugation of photoactivatable probes to various targets such as Halo-tag. Our probe is highly water-soluble, non-cytotoxic, and readily cell-permeable, which are optimal properties to study cellular process. In particular, we have applied our probe to study the misfolding of a-synuclein (aS), aggregates of which are hallmarks of Parkinson’s disease.  Potential utilization in a cell culture models of aS-seeded aggregation will allow us to better understand the intracellular processes involved inf aS aggregation. Our work allows biomolecular imaging in minimally perturbed systems to understand the dynamics of biomolecules.<br/>

Clickable photoconvertable diazaxanthilidene probe to study protein foldings in live cells

256th National Meeting (2018)

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