We are currently developing modified nucleos(t)ides as substrate mimics to provide insight into enzyme substrate recognition, as well as libraries of functionalized heterocycles useful for the fragment based approach. Novel enzymatic routes (transglycosylation, deamination, phosphorylation) as an alternative to chemical approaches are also considered. The synthesized molecules find applications in the identification of inhibitors of essential bacterial enzymes (TMPK from Mycobacterium tuberculosis, DNPH1, an N-hydrolase involved in cell proliferation, NAD kinases from Gram-positive bacteria). In addition, the new chemical entities implement the in house chemical libraries.
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2022Structure-based design, synthesis and biological evaluation of a NAD+ analogue targeting Pseudomonas aeruginosa NAD kinase., FEBS J 2022 Aug; (): .
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2021Noncanonical DNA polymerization by aminoadenine-based siphoviruses., Science 2021 04; 372(6541): 520-524.
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2020New Chemical Probe Targeting Bacterial NAD Kinase., Molecules 2020 Oct; 25(21): .
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2020Fermentation Products of Commensal Bacteria Alter Enterocyte Lipid Metabolism, Cell Host Microbe 2020 March 11;27:1-18.
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2020From Substrate to Fragments to Inhibitor Active In Vivo against Staphylococcus aureus., ACS Infect Dis 2020 03; 6(3): 422-435.
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2020An expedient synthesis of flexible nucleosides through enzymatic glycosylation of proximal and distal fleximer bases, Chembiochem 2020 Jan;.
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2019Crystal structure of the Trypanosoma cruzi EIF4E5 translation factor homologue in complex with mRNA cap-4, Nucleic Acids Res. 2019 Jun;47(11):5973-5987.
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2019First-in-class allosteric inhibitors of bacterial IMPDHs, Eur J Med Chem 2019 Feb;167:124-132.
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20192′-Deoxyribonucleoside 5′-triphosphates bearing 4-phenyl and 4-pyrimidinyl imidazoles as DNA polymerase substrates, Org. Biomol. Chem. 2019 01;17(2):290-301.
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2018Enzymatic synthesis of random sequences of RNA and RNA analogues by DNA polymerase theta mutants for the generation of aptamer libraries, Nucleic Acids Res. 2018 07;46(12):6271-6284.
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Phone: 33/1 40 61 38 05 Email: sylvie.pochet@pasteur.fr Address 25-28 Rue du Docteur Roux 75015, Paris France