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Two-Step Synthesis of Novel, Bioactive Derivatives of the Ubiquitous Cofactor Nicotinamide Adenine Dinucleotide (NAD)

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journal contribution
posted on 26.05.2011 by Thomas Pesnot, Julia Kempter, Jörg Schemies, Giulia Pergolizzi, Urszula Uciechowska, Tobias Rumpf, Wolfgang Sippl, Manfred Jung, Gerd K. Wagner
We report the design and concise synthesis, in two steps from commercially available material, of novel, bioactive derivatives of the enzyme cofactor nicotinamide adenine dinucleotide (NAD). The new synthetic dinucleotides act as sirtuin (SIRT) inhibitors and show isoform selectivity for SIRT2 over SIRT1. An NMR-based conformational analysis suggests that the conformational preferences of individual analogues may contribute to their isoform selectivity.