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

First Author  Huang K Year  2023
Journal  ACS Sens Volume  8
Issue  2 Pages  767-773
PubMed ID  36689294 Mgi Jnum  J:355531
Mgi Id  MGI:7719059 Doi  10.1021/acssensors.2c02317
Citation  Huang K, et al. (2023) Base-Exchange Enabling the Visualization of SARM1 Activities in Sciatic Nerve-Injured Mice. ACS Sens 8(2):767-773
abstractText  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.
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