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Project TitleAnalogs of a B Vitamin (Nicotinamide Riboside), New Synthesis Method, Uses
Track Code3787
Short Description
Abstract

Professor Sauve of the Weill Cornell Medical College's Department of Pharmacology, is one of the pioneers of sirtuin biochemistry. Sirtuins are class II HDACs and are ADP-ribosyl transferases. They deacetylate lysine residues in a novel chemical reaction that consumes nicotinamide adenine dinucleotide (NAD+), releasing nicotinamide, O-acetyl-ADP-ribose, and the deacetylated substrate. The seemingly baroque and energetically costly chemistry of sirtuins permits their enzymatic activity to be regulated by a variety of metabolites and may enable the enzyme to serve other chemical functions in addition to deacetylation.

 

In the course of investigating sirtuin biochemistry, Prof. Sauve has been part of a group of investigators re-invigorating the study of NAD metabolism and catabolism, and of the B vitamins. Altering intracellular NAD levels can improve or preserve the health of a cell, while certain compounds that enter NAD metabolic pathways can prove toxic or cytostatic.

 

NR is a known precursor of NAD and has been found naturally occuring in food. NR may therefore be considered a vitamin, and may have commercial value as a dietary supplement. Difficulties in large scale synthesis have hindered efforts to develop this aspect of NR's potential value; Prof. Sauve has developed highly efficient synthetic methods that may unlock that value.

 

Further, Prof. Sauve has used these synthetic methods to generate novel analogs of NR, some of which have proved cell-protective, others of which are toxic or cytostatic.

 

Professor Sauve's novel compounds and high efficiency synthetic methods provide opportunities to manipulate NAD levels and thereby to modulate the activity of sirtuins and other ADP-ribosyl transferases. The compounds can be used to destroy or weaken the defenses of cancer cells, to promote survival of neurons, myocytes, or stem cells, to hold stem cells in an undifferentiated state and promote their survival, or to reduce side effects caused by other therapeutics.

 
TagsCNS & PNS, cancer, cardiovascular, dietary supplement, life science, metabolic, small molecule, synthetic methods, endocrinology, synthesis
 
Posted DateJul 23, 2012 5:58 PM

Researcher

Name
Tianle Yang
Anthony Sauve

Additional Information

  • (2004) Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell. 117(4):495-502.
  • (2007) Sauve AA. NAD+ and Vitamin B3: From metabolism to therapies. J Pharmacol Exp Ther. Dec 28;
  • (2007) Yang H, et al. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell. 130(6):1095-107.
  • (2007) Yang T, Chan NY, Sauve AA. Syntheses of nicotinamide riboside and derivatives: effective agents for increasing nicotinamide adenine dinucleotide concentrations in Mammalian cells. J Med Chem. 50(26):6458-61

Licensing Contact

Brian J. Kelly
bjk44@cornell.edu
212-746-6186