Institute for Pharmacy and Food Chemistry

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Pharmaceutical and Medicinal Chemistry
Drug Formulation and Delivery
Food Chemistry

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Pharmacy (State Examination)
Food Chemistry (Bachelor/Master)

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Navigating chemical reaction space – application to DNA-encoded chemistry Chines, Silvia; Ehrt, Christiane; Potowski, Marco; Biesenkamp, Felix; Grützbach, Lars; Brunner, Susanne; van den Broek, Frederik; Bali, Shilpa; Ickstadt, Katja; Brunschweiger, Andreas in Chem. Sci. (2022). 13(37) 11221–11231.
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%0 Journal Article %1 D2SC02474H %A Chines, Silvia %A Ehrt, Christiane %A Potowski, Marco %A Biesenkamp, Felix %A Grützbach, Lars %A Brunner, Susanne %A van den Broek, Frederik %A Bali, Shilpa %A Ickstadt, Katja %A Brunschweiger, Andreas %D 2022 %I The Royal Society of Chemistry %J Chem. Sci. %N 37 %P 11221-11231 %R 10.1039/D2SC02474H %T Navigating chemical reaction space – application to DNA-encoded chemistry %U http://dx.doi.org/10.1039/D2SC02474H %V 13 %X Databases contain millions of reactions for compound synthesis, rendering selection of reactions for forward synthetic design of small molecule screening libraries, such as DNA-encoded libraries (DELs), a big data challenge. To support reaction space navigation, we developed the computational workflow Reaction Navigator. Reaction files from a large chemistry database were processed using the open-source KNIME Analytics Platform. Initial processing steps included a customizable filtering cascade that removed reactions with a high probability to be incompatible with DEL, as they would e.g. damage the genetic barcode, to arrive at a comprehensive list of transformations for DEL design with applicability potential. These reactions were displayed and clustered by user-defined molecular reaction descriptors which are independent of reaction core substitution patterns. Thanks to clustering, these can be searched manually to identify reactions for DEL synthesis according to desired reaction criteria, such as ring formation or sp3 content. The workflow was initially applied for mapping chemical reaction space for aromatic aldehydes as an exemplary functional group often used in DEL synthesis. Exemplary reactions have been successfully translated to DNA-tagged substrates and can be applied to library synthesis. The versatility of the Reaction Navigator was then shown by mapping reaction space for different reaction conditions, for amines as a second set of starting materials, and for data from a second database.
Glycolytic flux control by drugging phosphoglycolate phosphatase Jeanclos, Elisabeth; Schl"otzer, Jan; Hadamek, Kerstin; Yuan-Chen, Natalia; Alwahsh, Mohammad; Hollmann, Robert; Fratz, Stefanie; Yesilyurt-Gerhards, Dilan; Frankenbach, Tina; Engelmann, Daria; Keller, Angelika; Kaestner, Alexandra; Schmitz, Werner; Neuenschwander, Martin; Hergenr"oder, Roland; Sotriffer, Christoph; von Kries, Jens Peter; Schindelin, Hermann; Gohla, Antje in Nature Communications (2022). 13(1) 6845.
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%0 Journal Article %1 Jeanclos2022 %A Jeanclos, Elisabeth %A Schl"otzer, Jan %A Hadamek, Kerstin %A Yuan-Chen, Natalia %A Alwahsh, Mohammad %A Hollmann, Robert %A Fratz, Stefanie %A Yesilyurt-Gerhards, Dilan %A Frankenbach, Tina %A Engelmann, Daria %A Keller, Angelika %A Kaestner, Alexandra %A Schmitz, Werner %A Neuenschwander, Martin %A Hergenr"oder, Roland %A Sotriffer, Christoph %A von Kries, Jens Peter %A Schindelin, Hermann %A Gohla, Antje %D 2022 %J Nature Communications %N 1 %P 6845 %R 10.1038/s41467-022-34228-2 %T Glycolytic flux control by drugging phosphoglycolate phosphatase %U https://doi.org/10.1038/s41467-022-34228-2 %V 13 %X Targeting the intrinsic metabolism of immune or tumor cells is a therapeutic strategy in autoimmunity, chronic inflammation or cancer. Metabolite repair enzymes may represent an alternative target class for selective metabolic inhibition, but pharmacological tools to test this concept are needed. Here, we demonstrate that phosphoglycolate phosphatase (PGP), a prototypical metabolite repair enzyme in glycolysis, is a pharmacologically actionable target. Using a combination of small molecule screening, protein crystallography, molecular dynamics simulations and NMR metabolomics, we discover and analyze a compound (CP1) that inhibits PGP with high selectivity and submicromolar potency. CP1 locks the phosphatase in a catalytically inactive conformation, dampens glycolytic flux, and phenocopies effects of cellular PGP-deficiency. This study provides key insights into effective and precise PGP targeting, at the same time validating an allosteric approach to control glycolysis that could advance discoveries of innovative therapeutic candidates.
Towards DNA-Encoded Micellar Chemistry: DNA-Micelle Association and Environment Sensitivity of Catalysis vSkopi’c, Mateja Klika; Gramse, Christian; Oliva, Rosario; Pospich, Sabrina; Neukirch, Laura; Manisegaran, Magiliny; Raunser, Stefan; Winter, Roland; Weberskirch, Ralf; Brunschweiger, Andreas in Chemistry textendash A European Journal (2021). 27(39) 10048–10057.
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%0 Journal Article %1 Klika_kopi__2021 %A vSkopi'c, Mateja Klika %A Gramse, Christian %A Oliva, Rosario %A Pospich, Sabrina %A Neukirch, Laura %A Manisegaran, Magiliny %A Raunser, Stefan %A Winter, Roland %A Weberskirch, Ralf %A Brunschweiger, Andreas %D 2021 %I Wiley %J Chemistry textendash A European Journal %N 39 %P 10048--10057 %R 10.1002/chem.202100980 %T Towards DNA-Encoded Micellar Chemistry: DNA-Micelle Association and Environment Sensitivity of Catalysis %U https://doi.org/10.1002%2Fchem.202100980 %V 27

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Vom Ideengeber bis zum Geschäftsführer – das Team hinter dem diagnostischen Kaugummi (v.l.): Lorenz Meinel, Christian Linz, Heinrich Jehle, Peter Winklehner, Bianca Böpple und Iris Zwirner-Baier.

Diagnostic chewing gum on its way to the market

A chewing gum that warns of inflammation in the oral cavity: scientists at the University of Würzburg have been focusing on this clever idea for a long time.