Base-Exchange Enabling the Visualization of SARM1 Activities in Sciatic Nerve-Injured Mice.

Enzymes are important in homeostasis in living organisms. Since abnormal enzyme activities are highly associated with many human diseases, detection of in vivo activities of a specific enzyme is important to study the pathology of the related diseases. In this work, we have designed and synthesized a series of new small-molecule-activatable fluorescent probes for the imaging of Sterile Alpha and TIR Motif-containing 1 (SARM1) activities based on its transglycosidase activities (base-exchange reactions of NAD). Probe was found to undergo base-exchange reactions with NAD in the presence of activated SARM1 but not CD38 nor NADase and formed a highly emissive product AD- [about a 100-fold fluorescence enhancement in 20 min with a 150 nm (5665 cm) Stokes shift and a 100 nm (3812 cm) red shift]. This probe exhibited a higher reactivity and sensitivity than those commonly used for SARM1 imaging. The utilities of have also been demonstrated in live-cell imaging and detection of in vivo activities of SARM1 in a sciatic nerve injury mouse model.