Probing binding requirements of NAD kinase with modified substrate (NAD) analogues

Laurent Bonnac; Liqiang Chen; Rashmi Pathak; Guangyao Gao; Qian Ming; Eric Bennett; Krzysztof Felczak; Martin Kullberg; Steven E. Patterson; Francesca Mazzola; Giulio Magni; Krzysztof W. Pankiewicz

doi:10.1016/j.bmcl.2007.01.012

Probing binding requirements of NAD kinase with modified substrate (NAD) analogues

Laurent Bonnac, Liqiang Chen, Rashmi Pathak, Guangyao Gao, Qian Ming, Eric Bennett, Krzysztof Felczak, Martin Kullberg, Steven E. Patterson, Francesca Mazzola, Giulio Magni, Krzysztof W. Pankiewicz

Center for Drug Design

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Synthesis of novel NAD⁺ analogues that cannot be phosphorylated by NAD kinase is reported. In these analogues the C2′ hydroxyl group of the adenosine moiety was replaced by fluorine in the ribo or arabino configuration (1 and 2, respectively) or was inverted into arabino configuration to give compound 3. Compounds 1 and 2 showed inhibition of human NAD kinase, whereas analogue 3 inhibited both the human and Mycobacterium tuberculosis NAD kinase. An uncharged benzamide adenine dinucleotide (BAD) was found to be the most potent competitive inhibitor (K_i = 90 μM) of the human enzyme reported so far.

Original language	English (US)
Pages (from-to)	1512-1515
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	6
DOIs	https://doi.org/10.1016/j.bmcl.2007.01.012
State	Published - Mar 15 2007

Bibliographical note

Funding Information:
These studies were funded by the Center for Drug Design, University of Minnesota.

Keywords

Benzamide adenine dinucleotide (BAD)
M. tuberculosis
NAD analogues
NAD kinase

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Probing binding requirements of NAD kinase with modified substrate (NAD) analogues",

abstract = "Synthesis of novel NAD+ analogues that cannot be phosphorylated by NAD kinase is reported. In these analogues the C2′ hydroxyl group of the adenosine moiety was replaced by fluorine in the ribo or arabino configuration (1 and 2, respectively) or was inverted into arabino configuration to give compound 3. Compounds 1 and 2 showed inhibition of human NAD kinase, whereas analogue 3 inhibited both the human and Mycobacterium tuberculosis NAD kinase. An uncharged benzamide adenine dinucleotide (BAD) was found to be the most potent competitive inhibitor (Ki = 90 μM) of the human enzyme reported so far.",

keywords = "Benzamide adenine dinucleotide (BAD), M. tuberculosis, NAD analogues, NAD kinase",

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AU - Bonnac, Laurent

AU - Chen, Liqiang

AU - Pathak, Rashmi

AU - Gao, Guangyao

AU - Ming, Qian

AU - Bennett, Eric

AU - Felczak, Krzysztof

AU - Kullberg, Martin

AU - Patterson, Steven E.

AU - Mazzola, Francesca

AU - Magni, Giulio

AU - Pankiewicz, Krzysztof W.

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AB - Synthesis of novel NAD+ analogues that cannot be phosphorylated by NAD kinase is reported. In these analogues the C2′ hydroxyl group of the adenosine moiety was replaced by fluorine in the ribo or arabino configuration (1 and 2, respectively) or was inverted into arabino configuration to give compound 3. Compounds 1 and 2 showed inhibition of human NAD kinase, whereas analogue 3 inhibited both the human and Mycobacterium tuberculosis NAD kinase. An uncharged benzamide adenine dinucleotide (BAD) was found to be the most potent competitive inhibitor (Ki = 90 μM) of the human enzyme reported so far.

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KW - M. tuberculosis

KW - NAD analogues

KW - NAD kinase

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Probing binding requirements of NAD kinase with modified substrate (NAD) analogues

Abstract

Bibliographical note

Keywords

UN SDGs

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