Small-molecule fluorescent probes have emerged as an indispensible tool for chemical biology; however, despite the number of probes available, there is a need for a simple fluorogenic scaffold that allows rational design to generate molecules with predictable photophysical properties in efficient manner. Here, we introduce a highly modular fluorogenic azide probe containing four strategic domains that can be easily engineered and optimized for various applications. Such domains are allotted for 1) compound polarization 2) click-able ligation 3) tuning of photophysical properties and 4) sensing ions. We successfully synthesized our probe in three steps from commercially available starting materials in overall yields of up to &gt;80% in large scale. Facile synthesis of our probe was permitted by regioselective palladium-catalyzed cross coupling, which paves the way for combinatorial probe development. A library of probes has shown a significant turn-on fluorescence response upon click ligation to a target molecule and exhibited tunable absorption and emission, spanning the visible spectrum. We have further applied our probe to study the folding of α-synuclein (αS), aggregates of which are hallmarks of Parkinson’s disease. Most importantly, our turn-on probes allow live-cell imaging without wash out of excess dye providing the least perturbed system to understand the dynamics of biomolecules. Rational design and facile synthesis of chemical probes can provide tools for convenient, continuous assays for studying amyloidgenic proteins including αS in cellular environments.

Rational design and facile synthesis of highly modular turn-on fluorescent probe

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.