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Facile chemoenzymatic synthesis of a novel stable mimic of NAD+

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Abstract

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor participating in a variety of important enzyme-catalyzed physiological and pathophysiological processes. Analogues of NAD+ provide key and valuable agents for investigating NAD+-dependent enzymes. In this study, we report the preparation of a novel stable NAD+ mimic, 4′-thioribose NAD+ (S-NAD+), using a facile and efficient chemoenzymatic approach. Substrate activity assays indicated the resulting S-NAD+ is chemically inert to human CD38 and sirtuin 2 enzymes, but capable of participating in redox reactions in a manner similar to NAD+. X-ray crystallographic analysis revealed binding of S-NAD+ to the active site of human CD38 and critical residues involved in leaving group activation and catalysis. By more closely mimicking NAD+ in geometry and electrostatics, the generated S-NAD+ offers a unique and important tool that can be extended to study enzymes utilizing NAD+.

Graphical abstract: Facile chemoenzymatic synthesis of a novel stable mimic of NAD+

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Publication details

The article was received on 31 Aug 2018, accepted on 14 Oct 2018 and first published on 15 Oct 2018


Article type: Edge Article
DOI: 10.1039/C8SC03899F
Citation: Chem. Sci., 2018, Advance Article
  • Open access: Creative Commons BY-NC license
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    Facile chemoenzymatic synthesis of a novel stable mimic of NAD+

    Z. Dai, X. Zhang, F. Nasertorabi, Q. Cheng, H. Pei, S. G. Louie, R. C. Stevens and Y. Zhang, Chem. Sci., 2018, Advance Article , DOI: 10.1039/C8SC03899F

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