New Chemical Probe Targeting Bacterial NAD Kinase
Nicotinamide adenine dinucleotide (NAD) kinases are essential and ubiquitous enzymes involved in the tight regulation of NAD/nicotinamide adenine dinucleotide phosphate (NADP) levels in many metabolic pathways. Consequently, they represent promising therapeutic targets in cancer and antibacterial tr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/21/4893 |
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| author | David A. Clément Clarisse Leseigneur Muriel Gelin Dylan Coelho Valérie Huteau Corinne Lionne Gilles Labesse Olivier Dussurget Sylvie Pochet |
| author_facet | David A. Clément Clarisse Leseigneur Muriel Gelin Dylan Coelho Valérie Huteau Corinne Lionne Gilles Labesse Olivier Dussurget Sylvie Pochet |
| author_sort | David A. Clément |
| collection | DOAJ |
| description | Nicotinamide adenine dinucleotide (NAD) kinases are essential and ubiquitous enzymes involved in the tight regulation of NAD/nicotinamide adenine dinucleotide phosphate (NADP) levels in many metabolic pathways. Consequently, they represent promising therapeutic targets in cancer and antibacterial treatments. We previously reported diadenosine derivatives as NAD kinase inhibitors with bactericidal activities on <i>Staphylococcus aureus</i>. Among them, one compound (namely <b>NKI1</b>) was found effective in vivo in a mouse infection model. With the aim to gain detailed knowledge about the selectivity and mechanism of action of this lead compound, we planned to develop a chemical probe that could be used in affinity-based chemoproteomic approaches. Here, we describe the first functionalized chemical probe targeting a bacterial NAD kinase. Aminoalkyl functional groups were introduced on <b>NKI1</b> for further covalent coupling to an activated Sepharose<sup>TM</sup> matrix. Inhibitory properties of functionalized <b>NKI1</b> derivatives together with X-ray characterization of their complexes with the NAD kinase led to identify candidate compounds that are amenable to covalent coupling to a matrix. |
| first_indexed | 2024-03-10T15:24:28Z |
| format | Article |
| id | doaj.art-44ffd8ae00fd408e8ebb615e36417972 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:24:28Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-44ffd8ae00fd408e8ebb615e364179722023-11-20T18:11:23ZengMDPI AGMolecules1420-30492020-10-012521489310.3390/molecules25214893New Chemical Probe Targeting Bacterial NAD KinaseDavid A. Clément0Clarisse Leseigneur1Muriel Gelin2Dylan Coelho3Valérie Huteau4Corinne Lionne5Gilles Labesse6Olivier Dussurget7Sylvie Pochet8Institut Pasteur, Unité de Chimie et Biocatalyse, UMR3523 CNRS, 75015 Paris, FranceFaculté des Sciences, Université de Paris, Sorbonne Paris Cité, 75013 Paris, FranceCentre de Biochimie Structurale (CBS), CNRS, INSERM, Université de Montpellier, 34090 Montpellier, FranceInstitut Pasteur, Unité de Chimie et Biocatalyse, UMR3523 CNRS, 75015 Paris, FranceInstitut Pasteur, Unité de Chimie et Biocatalyse, UMR3523 CNRS, 75015 Paris, FranceCentre de Biochimie Structurale (CBS), CNRS, INSERM, Université de Montpellier, 34090 Montpellier, FranceCentre de Biochimie Structurale (CBS), CNRS, INSERM, Université de Montpellier, 34090 Montpellier, FranceFaculté des Sciences, Université de Paris, Sorbonne Paris Cité, 75013 Paris, FranceInstitut Pasteur, Unité de Chimie et Biocatalyse, UMR3523 CNRS, 75015 Paris, FranceNicotinamide adenine dinucleotide (NAD) kinases are essential and ubiquitous enzymes involved in the tight regulation of NAD/nicotinamide adenine dinucleotide phosphate (NADP) levels in many metabolic pathways. Consequently, they represent promising therapeutic targets in cancer and antibacterial treatments. We previously reported diadenosine derivatives as NAD kinase inhibitors with bactericidal activities on <i>Staphylococcus aureus</i>. Among them, one compound (namely <b>NKI1</b>) was found effective in vivo in a mouse infection model. With the aim to gain detailed knowledge about the selectivity and mechanism of action of this lead compound, we planned to develop a chemical probe that could be used in affinity-based chemoproteomic approaches. Here, we describe the first functionalized chemical probe targeting a bacterial NAD kinase. Aminoalkyl functional groups were introduced on <b>NKI1</b> for further covalent coupling to an activated Sepharose<sup>TM</sup> matrix. Inhibitory properties of functionalized <b>NKI1</b> derivatives together with X-ray characterization of their complexes with the NAD kinase led to identify candidate compounds that are amenable to covalent coupling to a matrix.https://www.mdpi.com/1420-3049/25/21/4893antibioticschemical probediadenosine derivativesNAD kinasenucleosideSonogashira coupling |
| spellingShingle | David A. Clément Clarisse Leseigneur Muriel Gelin Dylan Coelho Valérie Huteau Corinne Lionne Gilles Labesse Olivier Dussurget Sylvie Pochet New Chemical Probe Targeting Bacterial NAD Kinase Molecules antibiotics chemical probe diadenosine derivatives NAD kinase nucleoside Sonogashira coupling |
| title | New Chemical Probe Targeting Bacterial NAD Kinase |
| title_full | New Chemical Probe Targeting Bacterial NAD Kinase |
| title_fullStr | New Chemical Probe Targeting Bacterial NAD Kinase |
| title_full_unstemmed | New Chemical Probe Targeting Bacterial NAD Kinase |
| title_short | New Chemical Probe Targeting Bacterial NAD Kinase |
| title_sort | new chemical probe targeting bacterial nad kinase |
| topic | antibiotics chemical probe diadenosine derivatives NAD kinase nucleoside Sonogashira coupling |
| url | https://www.mdpi.com/1420-3049/25/21/4893 |
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