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Nicotinamide Riboside and CD38: Covalent Inhibition and Live-Cell Labeling.

Guoyun Kao1, Xiao-Nan Zhang1, Fariborz Nasertorabi2

  • 1Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, California 90089, United States.

JACS Au
|November 29, 2024
PubMed
Summary
This summary is machine-generated.

Nicotinamide riboside (NR) unexpectedly inhibits CD38, a key NAD+ degrading enzyme. Researchers developed a clickable NR probe for visualizing CD38 in live cells, advancing NAD+ metabolism research.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolic Pathways

Background:

  • Nicotinamide adenine dinucleotide (NAD+) is vital for cellular functions and its levels impact health.
  • Cluster of differentiation 38 (CD38) is a major enzyme that degrades NAD+.
  • Inhibiting CD38 can increase NAD+ levels and offer therapeutic benefits.

Purpose of the Study:

  • To investigate the potential of nicotinamide riboside (NR) to inhibit CD38.
  • To develop a tool for studying CD38's role in NAD+ metabolism and signaling.

Main Methods:

  • Exploration of NR's inhibitory activity against CD38.
  • Synthesis of a clickable NR analogue with azido substitution.
  • Covalent labeling and imaging of CD38 in live cells using the NR probe.

Main Results:

  • NR was found to inhibit CD38 by forming a stable bond at the active site.
  • A cell-permeable NR probe was successfully synthesized and used for CD38 visualization.
  • The probe allowed for labeling of both extracellular and intracellular CD38.

Conclusions:

  • NR possesses an unrecognized inhibitory function against CD38.
  • The developed NR probe is a valuable tool for studying CD38 in biological systems.
  • Findings provide new insights into NAD+ metabolism and CD38-mediated signaling.