Interactions of 2,6-substituted purines with purine nucleoside phosphorylase from Helicobacter pylori in solution and in the crystal, and the effects of these compounds on cell cultures of this bacterium
Helicobacter pylori represents a global health threat with around 50% of the world population infected. Due to the increasing number of antibiotic-resistant strains, new strategies for eradication of H. pylori are needed. In this study, we suggest purine nucleoside phosphorylase (PNP) as a possible...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2061965 |
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| author | Marta Narczyk Marta Ilona Wojtyś Ivana Leščić Ašler Biserka Žinić Marija Luić Elżbieta Katarzyna Jagusztyn-Krynicka Zoran Štefanić Agnieszka Bzowska |
| author_facet | Marta Narczyk Marta Ilona Wojtyś Ivana Leščić Ašler Biserka Žinić Marija Luić Elżbieta Katarzyna Jagusztyn-Krynicka Zoran Štefanić Agnieszka Bzowska |
| author_sort | Marta Narczyk |
| collection | DOAJ |
| description | Helicobacter pylori represents a global health threat with around 50% of the world population infected. Due to the increasing number of antibiotic-resistant strains, new strategies for eradication of H. pylori are needed. In this study, we suggest purine nucleoside phosphorylase (PNP) as a possible new drug target, by characterising its interactions with 2- and/or 6-substituted purines as well as the effect of these compounds on bacterial growth. Inhibition constants are in the micromolar range, the lowest being that of 6-benzylthio-2-chloropurine. This compound also inhibits H. pylori 26695 growth at the lowest concentration. X-ray structures of the complexes of PNP with the investigated compounds allowed the identification of interactions of inhibitors in the enzyme’s base-binding site and the suggestion of structures that could bind to the enzyme more tightly. Our findings prove the potential of PNP inhibitors in the design of drugs against H. pylori. |
| format | Article |
| id | doaj-art-b8e2c6ef5de44b0fb211f30cc3691fae |
| institution | OA Journals |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-b8e2c6ef5de44b0fb211f30cc3691fae2025-08-20T02:10:20ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013711083109710.1080/14756366.2022.2061965Interactions of 2,6-substituted purines with purine nucleoside phosphorylase from Helicobacter pylori in solution and in the crystal, and the effects of these compounds on cell cultures of this bacteriumMarta Narczyk0Marta Ilona Wojtyś1Ivana Leščić Ašler2Biserka Žinić3Marija Luić4Elżbieta Katarzyna Jagusztyn-Krynicka5Zoran Štefanić6Agnieszka Bzowska7Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, PolandDivision of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, PolandDivision of Physical Chemistry, Ruđer Bošković Institute, Zagreb, CroatiaDivision of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, CroatiaDivision of Physical Chemistry, Ruđer Bošković Institute, Zagreb, CroatiaDepartment of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Warsaw, PolandDivision of Physical Chemistry, Ruđer Bošković Institute, Zagreb, CroatiaDivision of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, PolandHelicobacter pylori represents a global health threat with around 50% of the world population infected. Due to the increasing number of antibiotic-resistant strains, new strategies for eradication of H. pylori are needed. In this study, we suggest purine nucleoside phosphorylase (PNP) as a possible new drug target, by characterising its interactions with 2- and/or 6-substituted purines as well as the effect of these compounds on bacterial growth. Inhibition constants are in the micromolar range, the lowest being that of 6-benzylthio-2-chloropurine. This compound also inhibits H. pylori 26695 growth at the lowest concentration. X-ray structures of the complexes of PNP with the investigated compounds allowed the identification of interactions of inhibitors in the enzyme’s base-binding site and the suggestion of structures that could bind to the enzyme more tightly. Our findings prove the potential of PNP inhibitors in the design of drugs against H. pylori.https://www.tandfonline.com/doi/10.1080/14756366.2022.2061965Helicobacter pyloripurine nucleoside phosphorylasesubstituted purinesminimal inhibitory concentrationX-ray structure |
| spellingShingle | Marta Narczyk Marta Ilona Wojtyś Ivana Leščić Ašler Biserka Žinić Marija Luić Elżbieta Katarzyna Jagusztyn-Krynicka Zoran Štefanić Agnieszka Bzowska Interactions of 2,6-substituted purines with purine nucleoside phosphorylase from Helicobacter pylori in solution and in the crystal, and the effects of these compounds on cell cultures of this bacterium Journal of Enzyme Inhibition and Medicinal Chemistry Helicobacter pylori purine nucleoside phosphorylase substituted purines minimal inhibitory concentration X-ray structure |
| title | Interactions of 2,6-substituted purines with purine nucleoside phosphorylase from Helicobacter pylori in solution and in the crystal, and the effects of these compounds on cell cultures of this bacterium |
| title_full | Interactions of 2,6-substituted purines with purine nucleoside phosphorylase from Helicobacter pylori in solution and in the crystal, and the effects of these compounds on cell cultures of this bacterium |
| title_fullStr | Interactions of 2,6-substituted purines with purine nucleoside phosphorylase from Helicobacter pylori in solution and in the crystal, and the effects of these compounds on cell cultures of this bacterium |
| title_full_unstemmed | Interactions of 2,6-substituted purines with purine nucleoside phosphorylase from Helicobacter pylori in solution and in the crystal, and the effects of these compounds on cell cultures of this bacterium |
| title_short | Interactions of 2,6-substituted purines with purine nucleoside phosphorylase from Helicobacter pylori in solution and in the crystal, and the effects of these compounds on cell cultures of this bacterium |
| title_sort | interactions of 2 6 substituted purines with purine nucleoside phosphorylase from helicobacter pylori in solution and in the crystal and the effects of these compounds on cell cultures of this bacterium |
| topic | Helicobacter pylori purine nucleoside phosphorylase substituted purines minimal inhibitory concentration X-ray structure |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2061965 |
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