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

Ke Huang, Wen Jie Zhu, Wan Hua Li, Hon Cheung Lee*, Yong Juan Zhao*, Chi-Sing Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 1a 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-1a [about a 100-fold fluorescence enhancement in 20 min with a 150 nm (5665 cm-1) Stokes shift and a 100 nm (3812 cm-1) red shift]. This probe exhibited a higher reactivity and sensitivity than those commonly used for SARM1 imaging. The utilities of 1a have also been demonstrated in live-cell imaging and detection of in vivo activities of SARM1 in a sciatic nerve injury mouse model.

Original languageEnglish
Number of pages7
JournalACS Sensors
DOIs
Publication statusE-pub ahead of print - 23 Jan 2023

User-Defined Keywords

  • base-exchange
  • enzyme activities
  • in vivo imaging
  • SARM1
  • activatable fluorescent probes

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