Propofol is a widely used general anesthetic, which acts by binding to and modulating several
neuronal ion channels. We describe the synthesis of photoactivatable propofol analogs
functionalized with an alkyne handle for bioorthogonal chemistry. Such tools are useful for
detecting and isolating photolabeled proteins. We designed expedient and flexible synthetic
routes to three new diazirine-based crosslinkable propofol derivatives, two of which have alkyne
handles. As a proof of principle, we show that these compounds activate heterologously
expressed Transient Receptor Potential Ankyrin 1 (TRPA1), a key ion channel of the pain
pathway, with a similar potency as propofol in fluorescence-based functional assays. This work
demonstrates that installation of the crosslinkable and clickable group on a short nonpolar spacer
at the para position of propofol does not affect TRPA1 activation, supporting the utility of these
chemical tools in identifying and characterizing potentially druggable binding sites in propofolinteracting proteins.
MP03-05 OPIOID ALTERNATIVE OUTPATIENT MALE ANTERIOR URETHROPLASTY PAIN PATHWAY: EVIDENCE FOR CHANGE
