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Facile chemoenzymatic synthesis of a novel stable mimic of NAD.

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+.

SUBMITTER: Dai Z

PROVIDER: S-EPMC6256357 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Facile chemoenzymatic synthesis of a novel stable mimic of NAD.

Dai Zhefu Z Zhang Xiao-Nan XN Nasertorabi Fariborz F Cheng Qinqin Q Pei Hua H Louie Stan G SG Stevens Raymond C RC Zhang Yong Y

Chemical science 20181015 44

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 activit ...[more]

PMID: 30568770

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