Just Published - Institute for Pharmacy and Food Chemistry

Simultaneous Determination of the Saponification Value, Acid Value, Ester Value, and Iodine Value in Commercially Available Red Fruit Oil (Pandanus conoideus, Lam.) Using 1H qNMR Spectroscopy Triyasmono, Liling; Schollmayer, Curd; Schmitz, Jens; Hovah, Emilie; Lombo, Cristian; Schmidt, Sebastian; Holzgrabe, Ulrike in Food Analytical Methods (2023). 16(1) 155–167.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Triyasmono2023
%A Triyasmono, Liling
%A Schollmayer, Curd
%A Schmitz, Jens
%A Hovah, Emilie
%A Lombo, Cristian
%A Schmidt, Sebastian
%A Holzgrabe, Ulrike
%D 2023
%J Food Analytical Methods
%N 1
%P 155--167
%R 10.1007/s12161-022-02401-4
%T Simultaneous Determination of the Saponification Value, Acid Value, Ester Value, and Iodine Value in Commercially Available Red Fruit Oil (Pandanus conoideus, Lam.) Using 1H qNMR Spectroscopy
%U https://doi.org/10.1007/s12161-022-02401-4
%V 16
%X Red fruit oil (RFO) can be extracted from fruits of Pandanus conoideus, Lam., an endogenous plant of Papua, Indonesia. It is a commonly used essential original traditional medicine. By applying a newly developed quantitative 1H NMR (qNMR) spectroscopy method for quality assessment, a simultaneous determination of the saponification value (SV), acid value (AV), ester value (EV), and iodine value (IV) in RFO was possible. Dimethyl sulfone (DMSO2) was used as an internal standard. Optimization of NMR parameters, such as NMR pulse sequence, relaxation delay time, and receiver gain, finally established the 1H NMR-based quantification approach. Diagnostic signals of the internal standard at \($\delta$\)thinspace=thinspace2.98 ppm, SV at \($\delta$\)thinspace=thinspace2.37--2.20 ppm, AV at \($\delta$\)thinspace=thinspace2.27--2.20 ppm, EV at \($\delta$\)thinspace=thinspace2.37--2.27 ppm, and IV at \($\delta$\)thinspace=thinspace5.37--5.27 ppm, respectively, were used for quantitative analysis. The method was validated concerning linearity (R2\thinspace=\thinspace0.999), precision (less than 0.83\%), and repeatability in the range 99.17--101.17%. Furthermore, this method was successfully applied to crude RFO, crude RFO with palmitic and oleic acid addition, and nine commercial products. The qNMR results for the respective fat values are in accordance with the results of standard methods, as can be seen from the F- and t-test (<\thinspace1.65 and\thinspace<\thinspace1.66, respectively). The fundamental advantages of qNMR, such as its rapidity and simplicity, make it a feasible and existing alternative to titration for the quality control of RFO.

Bridging the Binding Sites: Dualsteric Ligands for the Cannabinoid 2 Receptor (CB2R) Tutov, Anna; Steinmüller, Sophie A. M.; Ram’irez, Yesid A.; Jack, Christine E.; Rodr’iguez-Soacha, Diego A.; Sotriffer, Christoph; Hislop, James N.; Decker, Michael in Advanced Therapeutics (2023). 2200260.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Tutov_2023
%A Tutov, Anna
%A Steinmüller, Sophie A. M.
%A Ram'irez, Yesid A.
%A Jack, Christine E.
%A Rodr'iguez-Soacha, Diego A.
%A Sotriffer, Christoph
%A Hislop, James N.
%A Decker, Michael
%D 2023
%I Wiley
%J Advanced Therapeutics
%P 2200260
%R 10.1002/adtp.202200260
%T Bridging the Binding Sites: Dualsteric Ligands for the Cannabinoid 2 Receptor (CB2R)
%U https://doi.org/10.1002%2Fadtp.202200260

Method Development, Optimization, and Validation of the Separation of Ketamine Enantiomers by Capillary Electrophoresis Using Design of Experiments Schmidt, Sebastian; Holzgrabe, Ulrike in Chromatographia (2023). 86(1) 87–95.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Schmidt2023
%A Schmidt, Sebastian
%A Holzgrabe, Ulrike
%D 2023
%J Chromatographia
%N 1
%P 87--95
%R 10.1007/s10337-022-04229-w
%T Method Development, Optimization, and Validation of the Separation of Ketamine Enantiomers by Capillary Electrophoresis Using Design of Experiments
%U https://doi.org/10.1007/s10337-022-04229-w
%V 86
%X Capillary electrophoresis was chosen as cost-effective and robust method to separate ketamine enantiomers. For the method development, first different native and modified cyclodextrins were tested. The most promising chiral selector was \($\alpha$\)-cyclodextrin. A design of experiments (DoE) was carried out, which started with the screening of relevant factors. Based on these results, the method was optimized according to the significant factors (buffer, cyclodextrin concentration, pH value, voltage, temperature) of the screening based on the response resolution and migration time of the later migrating enantiomer. The optimized conditions consisted of a background electrolyte with 275 mM TRIS, adjusted with 85% phosphoric acid to a pH of 2.50, and 50 mM \($\alpha$\)-cyclodextrin, at a temperature of 15 textdegreeC, an applied voltage of 30 kV and an injection pressure of 1.0 psi for 10 s. A fused-silica capillary with a total length of 70 cm and an effective length to the detector of 60 cm was used. The method was validated according to ICH guideline Q2 R(1). The limit of quantification was 3.51 textmug mL−1 for S-ketamine and 3.98 textmug mL−1 for R-ketamine. The method showed good linearity for racemic ketamine with R2 of 0.9995 for S-ketamine and 0.9994 for R-ketamine. The lowest quantifiable content of S-ketamine found in R-ketamine was 0.45%.

Simultaneous Determination of the Saponification Value, Acid Value, Ester Value, and Iodine Value in Commercially Available Red Fruit Oil (Pandanus conoideus, Lam.) Using 1H qNMR Spectroscopy Triyasmono, Liling; Schollmayer, Curd; Schmitz, Jens; Hovah, Emilie; Lombo, Cristian; Schmidt, Sebastian; Holzgrabe, Ulrike in Food Analytical Methods (2023). 16(1) 155–167.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Triyasmono2023
%A Triyasmono, Liling
%A Schollmayer, Curd
%A Schmitz, Jens
%A Hovah, Emilie
%A Lombo, Cristian
%A Schmidt, Sebastian
%A Holzgrabe, Ulrike
%D 2023
%J Food Analytical Methods
%N 1
%P 155--167
%R 10.1007/s12161-022-02401-4
%T Simultaneous Determination of the Saponification Value, Acid Value, Ester Value, and Iodine Value in Commercially Available Red Fruit Oil (Pandanus conoideus, Lam.) Using 1H qNMR Spectroscopy
%U https://doi.org/10.1007/s12161-022-02401-4
%V 16
%X Red fruit oil (RFO) can be extracted from fruits of Pandanus conoideus, Lam., an endogenous plant of Papua, Indonesia. It is a commonly used essential original traditional medicine. By applying a newly developed quantitative 1H NMR (qNMR) spectroscopy method for quality assessment, a simultaneous determination of the saponification value (SV), acid value (AV), ester value (EV), and iodine value (IV) in RFO was possible. Dimethyl sulfone (DMSO2) was used as an internal standard. Optimization of NMR parameters, such as NMR pulse sequence, relaxation delay time, and receiver gain, finally established the 1H NMR-based quantification approach. Diagnostic signals of the internal standard at \($\delta$\)thinspace=thinspace2.98 ppm, SV at \($\delta$\)thinspace=thinspace2.37--2.20 ppm, AV at \($\delta$\)thinspace=thinspace2.27--2.20 ppm, EV at \($\delta$\)thinspace=thinspace2.37--2.27 ppm, and IV at \($\delta$\)thinspace=thinspace5.37--5.27 ppm, respectively, were used for quantitative analysis. The method was validated concerning linearity (R2\thinspace=\thinspace0.999), precision (less than 0.83\%), and repeatability in the range 99.17--101.17%. Furthermore, this method was successfully applied to crude RFO, crude RFO with palmitic and oleic acid addition, and nine commercial products. The qNMR results for the respective fat values are in accordance with the results of standard methods, as can be seen from the F- and t-test (<\thinspace1.65 and\thinspace<\thinspace1.66, respectively). The fundamental advantages of qNMR, such as its rapidity and simplicity, make it a feasible and existing alternative to titration for the quality control of RFO.

Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major Iwasaki, Jua; Lorimer, Donald D.; Vivoli-Vega, Mirella; Kibble, Emily A.; Peacock, Christopher S.; Abendroth, Jan; Mayclin, Stephen J.; Dranow, David M.; Pierce, Phillip G.; Fox, David; Lewis, Maria; Bzdyl, Nicole M.; Kristensen, Sofie S.; Inglis, Timothy J. J.; Kahler, Charlene M.; Bond, Charles S.; Hasenkopf, Anja; Seufert, Florian; Schmitz, Jens; Marshall, Laura E.; Scott, Andrew E.; Norville, Isobel H.; Myler, Peter J.; Holzgrabe, Ulrike; Harmer, Nicholas J.; Sarkar-Tyson, Mitali in Journal of Antimicrobial Chemotherapy (2022). 77(6) 1625–1634.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Iwasaki_2022
%A Iwasaki, Jua
%A Lorimer, Donald D.
%A Vivoli-Vega, Mirella
%A Kibble, Emily A.
%A Peacock, Christopher S.
%A Abendroth, Jan
%A Mayclin, Stephen J.
%A Dranow, David M.
%A Pierce, Phillip G.
%A Fox, David
%A Lewis, Maria
%A Bzdyl, Nicole M.
%A Kristensen, Sofie S.
%A Inglis, Timothy J. J.
%A Kahler, Charlene M.
%A Bond, Charles S.
%A Hasenkopf, Anja
%A Seufert, Florian
%A Schmitz, Jens
%A Marshall, Laura E.
%A Scott, Andrew E.
%A Norville, Isobel H.
%A Myler, Peter J.
%A Holzgrabe, Ulrike
%A Harmer, Nicholas J.
%A Sarkar-Tyson, Mitali
%D 2022
%I Oxford University Press (OUP)
%J Journal of Antimicrobial Chemotherapy
%N 6
%P 1625--1634
%R 10.1093/jac/dkac065
%T Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major
%U https://doi.org/10.1093%2Fjac%2Fdkac065
%V 77

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.

[ EndNote ]
[ URL ]
[ DOI ]

%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.

Fragment screening using biolayer interferometry reveals ligands targeting the SHP-motif binding site of the AAA+ ATPase p97 Bothe, Sebastian; H"anzelmann, Petra; B"ohler, Stephan; Kehrein, Josef; Zehe, Markus; Wiedemann, Christoph; Hellmich, Ute A.; Brenk, Ruth; Schindelin, Hermann; Sotriffer, Christoph in Communications Chemistry (2022). 5(1) 169.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Bothe2022
%A Bothe, Sebastian
%A H"anzelmann, Petra
%A B"ohler, Stephan
%A Kehrein, Josef
%A Zehe, Markus
%A Wiedemann, Christoph
%A Hellmich, Ute A.
%A Brenk, Ruth
%A Schindelin, Hermann
%A Sotriffer, Christoph
%D 2022
%J Communications Chemistry
%N 1
%P 169
%R 10.1038/s42004-022-00782-5
%T Fragment screening using biolayer interferometry reveals ligands targeting the SHP-motif binding site of the AAA+ ATPase p97
%U https://doi.org/10.1038/s42004-022-00782-5
%V 5
%X Biosensor techniques have become increasingly important for fragment-based drug discovery during the last years. The AAA+ ATPase p97 is an essential protein with key roles in protein homeostasis and a possible target for cancer chemotherapy. Currently available p97 inhibitors address its ATPase activity and globally impair p97-mediated processes. In contrast, inhibition of cofactor binding to the N-domain by a protein-protein-interaction inhibitor would enable the selective targeting of specific p97 functions. Here, we describe a biolayer interferometry-based fragment screen targeting the N-domain of p97 and demonstrate that a region known as SHP-motif binding site can be targeted with small molecules. Guided by molecular dynamics simulations, the binding sites of selected screening hits were postulated and experimentally validated using protein- and ligand-based NMR techniques, as well as X-ray crystallography, ultimately resulting in the first structure of a small molecule in complex with the N-domain of p97. The identified fragments provide insights into how this region could be targeted and present first chemical starting points for the development of a protein-protein interaction inhibitor preventing the binding of selected cofactors to p97.

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.

[ EndNote ]
[ URL ]
[ DOI ]

%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.

[ EndNote ]
[ URL ]
[ DOI ]

%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

Copper(I/II)-Promoted Diverse Imidazo[1,2-$$\upalpha$$]pyridine Synthesis on Solid-Phase Bound DNA Oligonucleotides for Encoded Library Design Potowski, Marco; Lüttig, Ricarda; Vakalopoulos, Alexandros; Brunschweiger, Andreas in Organic Letters (2021). 23(14) 5480–5484.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Potowski_2021
%A Potowski, Marco
%A Lüttig, Ricarda
%A Vakalopoulos, Alexandros
%A Brunschweiger, Andreas
%D 2021
%I American Chemical Society (ACS)
%J Organic Letters
%N 14
%P 5480--5484
%R 10.1021/acs.orglett.1c01834
%T Copper(I/II)-Promoted Diverse Imidazo[1,2-\($\upalpha$\)]pyridine Synthesis on Solid-Phase Bound DNA Oligonucleotides for Encoded Library Design
%U https://doi.org/10.1021%2Facs.orglett.1c01834
%V 23

Design of an Automated Reagent-Dispensing System for Reaction Screening and Validation with DNA-Tagged Substrates Bobers, Jens; vSkopi’c, Mateja Klika; Dinter, Robin; Sakthithasan, Piriyanth; Neukirch, Laura; Gramse, Christian; Weberskirch, Ralf; Brunschweiger, Andreas; Kockmann, Norbert in ACS Combinatorial Science (2020). 22(3) 101–108.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Bobers_2020
%A Bobers, Jens
%A vSkopi'c, Mateja Klika
%A Dinter, Robin
%A Sakthithasan, Piriyanth
%A Neukirch, Laura
%A Gramse, Christian
%A Weberskirch, Ralf
%A Brunschweiger, Andreas
%A Kockmann, Norbert
%D 2020
%I American Chemical Society (ACS)
%J ACS Combinatorial Science
%N 3
%P 101--108
%R 10.1021/acscombsci.9b00207
%T Design of an Automated Reagent-Dispensing System for Reaction Screening and Validation with DNA-Tagged Substrates
%U https://doi.org/10.1021%2Facscombsci.9b00207
%V 22

Reaction development for DNA-encoded library technology: From evolution to revolution? Götte, Katharina; Chines, Silvia; Brunschweiger, Andreas in Tetrahedron Letters (2020). 61(22) 151889.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 G_tte_2020
%A Götte, Katharina
%A Chines, Silvia
%A Brunschweiger, Andreas
%D 2020
%I Elsevier BV
%J Tetrahedron Letters
%N 22
%P 151889
%R 10.1016/j.tetlet.2020.151889
%T Reaction development for DNA-encoded library technology: From evolution to revolution?
%U https://doi.org/10.1016%2Fj.tetlet.2020.151889
%V 61

Translation of the copper/bipyridine-promoted Petasis reaction to solid phase-coupled DNA for encoded library synthesis Potowski, Marco; Esken, Robin; Brunschweiger, Andreas in Bioorganic \&amp$$\mathsemicolon$$ Medicinal Chemistry (2020). 28(9) 115441.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Potowski_2020
%A Potowski, Marco
%A Esken, Robin
%A Brunschweiger, Andreas
%D 2020
%I Elsevier BV
%J Bioorganic \&\($\mathsemicolon$\) Medicinal Chemistry
%N 9
%P 115441
%R 10.1016/j.bmc.2020.115441
%T Translation of the copper/bipyridine-promoted Petasis reaction to solid phase-coupled DNA for encoded library synthesis
%U https://doi.org/10.1016%2Fj.bmc.2020.115441
%V 28

Screening of metal ions and organocatalysts on solid support-coupled DNA oligonucleotides guides design of DNA-encoded reactions Potowski, Marco; Losch, Florian; Wünnemann, Elena; Dahmen, Janina K.; Chines, Silvia; Brunschweiger, Andreas in Chem. Sci. (2019). 10(45) 10481–10492.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 C9SC04708E
%A Potowski, Marco
%A Losch, Florian
%A Wünnemann, Elena
%A Dahmen, Janina K.
%A Chines, Silvia
%A Brunschweiger, Andreas
%D 2019
%I The Royal Society of Chemistry
%J Chem. Sci.
%N 45
%P 10481-10492
%R 10.1039/C9SC04708E
%T Screening of metal ions and organocatalysts on solid support-coupled DNA oligonucleotides guides design of DNA-encoded reactions
%U http://dx.doi.org/10.1039/C9SC04708E
%V 10
%X DNA-encoded compound libraries are a widely used technology for target-based small molecule screening. Generally, these libraries are synthesized by solution phase combinatorial chemistry requiring aqueous solvent mixtures and reactions that are orthogonal to DNA reactivity. Initiating library synthesis with readily available controlled pore glass-coupled DNA barcodes benefits from enhanced DNA stability due to nucleobase protection and choice of dry organic solvents for encoded compound synthesis. We screened the compatibility of solid-phase coupled DNA sequences with 53 metal salts and organic reagents. This screening experiment suggests design of encoded library synthesis. Here, we show the reaction optimization and scope of three sp3-bond containing heterocyclic scaffolds synthesized on controlled pore glass-connected DNA sequences. A ZnCl2-promoted aza-Diels–Alder reaction with Danishefsky's diene furnished diverse substituted DNA-tagged pyridones, and a phosphoric acid organocatalyst allowed for synthesis of tetrahydroquinolines by the Povarov reaction and pyrimidinones by the Biginelli reaction, respectively. These three reactions caused low levels of DNA depurination and cover broad and only partially overlapping chemical space though using one set of DNA-coupled starting materials.

Synthesis of DNA-coupled isoquinolones and pyrrolidines by solid phase ytterbium- and silver-mediated imine chemistry Potowski, Marco; Kunig, Verena B. K.; Losch, Florian; Brunschweiger, Andreas in Med. Chem. Commun. (2019). 10(7) 1082–1093.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 C9MD00042A
%A Potowski, Marco
%A Kunig, Verena B. K.
%A Losch, Florian
%A Brunschweiger, Andreas
%D 2019
%I The Royal Society of Chemistry
%J Med. Chem. Commun.
%N 7
%P 1082-1093
%R 10.1039/C9MD00042A
%T Synthesis of DNA-coupled isoquinolones and pyrrolidines by solid phase ytterbium- and silver-mediated imine chemistry
%U http://dx.doi.org/10.1039/C9MD00042A
%V 10
%X DNA-encoded libraries of chemically synthesized compounds are an important small molecule screening technology. The synthesis of encoded compounds in solution is currently restricted to a few DNA-compatible and water-tolerant reactions. Encoded compound synthesis of short DNA-barcodes covalently connected to solid supports benefits from a broad range of choices of organic solvents. Here, we show that this encoded chemistry approach allows for the synthesis of DNA-coupled isoquinolones by an Yb(iii)-mediated Castagnoli–Cushman reaction under anhydrous reaction conditions and for the synthesis of highly substituted pyrrolidines by Ag(i)-mediated 1,3-dipolar azomethine ylide cycloaddition. An encoding scheme for these DNA-barcoded compounds based on a DNA hairpin is demonstrated.

Towards Improved Oligonucleotide Therapeutics Through Faster Target Binding Kinetics Menzi, Mirjam; Wild, Bettina; Prad`ere, Ugo; Malinowska, Anna L.; Brunschweiger, Andreas; Lightfoot, Helen L.; Hall, Jonathan in Chemistry - A European Journal (2017). 23(57) 14221–14230.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Menzi_2017
%A Menzi, Mirjam
%A Wild, Bettina
%A Prad`ere, Ugo
%A Malinowska, Anna L.
%A Brunschweiger, Andreas
%A Lightfoot, Helen L.
%A Hall, Jonathan
%D 2017
%I Wiley
%J Chemistry - A European Journal
%N 57
%P 14221--14230
%R 10.1002/chem.201701670
%T Towards Improved Oligonucleotide Therapeutics Through Faster Target Binding Kinetics
%U https://doi.org/10.1002%2Fchem.201701670
%V 23

Design and synthesis of DNA-encoded libraries based on a benzodiazepine and a pyrazolopyrimidine scaffold Škopić, M. Klika; Bugain, O.; Jung, K.; Onstein, S.; Brandherm, S.; Kalliokoski, T.; Brunschweiger, A. in Med. Chem. Commun. (2016). 7(10) 1957–1965.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 C6MD00243A
%A Škopić, M. Klika
%A Bugain, O.
%A Jung, K.
%A Onstein, S.
%A Brandherm, S.
%A Kalliokoski, T.
%A Brunschweiger, A.
%D 2016
%I The Royal Society of Chemistry
%J Med. Chem. Commun.
%N 10
%P 1957-1965
%R 10.1039/C6MD00243A
%T Design and synthesis of DNA-encoded libraries based on a benzodiazepine and a pyrazolopyrimidine scaffold
%U http://dx.doi.org/10.1039/C6MD00243A
%V 7
%X Selection-based screening of large DNA-encoded libraries of drug-like small molecules is a validated method to identify bioactive compounds. Among the chemical space of bioactive compounds certain scaffold structures are well represented. These are commonly called “privileged scaffolds”. We have synthesized DNA-encoded libraries based on two representatives of these scaffolds, a benzodiazepine and a pyrazolopyrimidine, and additionally a third library based on propargyl glycine. All three core structures possess a carboxylic acid to couple them to aminolinker-modified DNA. For subsequent library synthesis they contained an amino function to which a set of carboxylic acid building blocks were coupled, and a terminal alkyne that was reacted with a set of azides to furnish triazoles. The two sets of building blocks, 114 carboxylic acids and 104 azides, were selected with the help of chemoinformatic methods in order to control the physicochemical properties of the final libraries, remove unwanted substructures, and maximize diversity. The set of building blocks contained desthiobiotin allowing for validation of library synthesis. The DNA-encoded libraries were synthesized by split-and-pool combinatorial chemistry yielding three libraries that contain 28.254 compounds together. For DNA barcoding, 5′-phosphorylated double-stranded coding DNA sequences with four base overhangs were ligated with T4 ligase. The resulting DNA-encoded libraries were compared to bioactivity databases and, though being based on core structures well-established in medicinal chemistry, showed novelty with respect to the known bioactive chemical space.

1,3-Dialkyl-substituted tetrahydropyrimido[1,2-f]purine-2,4-diones as multiple target drugs for the potential treatment of neurodegenerative diseases Koch, Pierre; Akkari, Rhalid; Brunschweiger, Andreas; Borrmann, Thomas; Schlenk, Miriam; Küppers, Petra; Köse, Meryem; Radjainia, Hamid; Hockemeyer, Jörg; Drabczy’nska, Anna; Kie’c-Kononowicz, Katarzyna; Müller, Christa E. in Bioorganic \&amp$$\mathsemicolon$$ Medicinal Chemistry (2013). 21(23) 7435–7452.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Koch_2013
%A Koch, Pierre
%A Akkari, Rhalid
%A Brunschweiger, Andreas
%A Borrmann, Thomas
%A Schlenk, Miriam
%A Küppers, Petra
%A Köse, Meryem
%A Radjainia, Hamid
%A Hockemeyer, Jörg
%A Drabczy'nska, Anna
%A Kie'c-Kononowicz, Katarzyna
%A Müller, Christa E.
%D 2013
%I Elsevier BV
%J Bioorganic \&\($\mathsemicolon$\) Medicinal Chemistry
%N 23
%P 7435--7452
%R 10.1016/j.bmc.2013.09.044
%T 1,3-Dialkyl-substituted tetrahydropyrimido[1,2-f]purine-2,4-diones as multiple target drugs for the potential treatment of neurodegenerative diseases
%U https://doi.org/10.1016%2Fj.bmc.2013.09.044
%V 21

Chemical Synthesis of Mono- and Bis-Labeled Pre-MicroRNAs Prad`ere, Ugo; Brunschweiger, Andreas; Gebert, Luca F. R.; Lucic, Matije; Roos, Martina; Hall, Jonathan in Angewandte Chemie International Edition (2013). 52(46) 12028–12032.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Prad_re_2013
%A Prad`ere, Ugo
%A Brunschweiger, Andreas
%A Gebert, Luca F. R.
%A Lucic, Matije
%A Roos, Martina
%A Hall, Jonathan
%D 2013
%I Wiley
%J Angewandte Chemie International Edition
%N 46
%P 12028--12032
%R 10.1002/anie.201304986
%T Chemical Synthesis of Mono- and Bis-Labeled Pre-MicroRNAs
%U https://doi.org/10.1002%2Fanie.201304986
%V 52

Virtual Screening Identifies Novel Sulfonamide Inhibitors of ecto-5’-Nucleotidase Ripphausen, Peter; Freundlieb, Marianne; Brunschweiger, Andreas; Zimmermann, Herbert; Müller, Christa E.; Bajorath, Jürgen in Journal of Medicinal Chemistry (2012). 55(14) 6576–6581.

[ EndNote ]
[ URL ]
[ DOI ]

%0 Journal Article
%1 Ripphausen_2012
%A Ripphausen, Peter
%A Freundlieb, Marianne
%A Brunschweiger, Andreas
%A Zimmermann, Herbert
%A Müller, Christa E.
%A Bajorath, Jürgen
%D 2012
%I American Chemical Society (ACS)
%J Journal of Medicinal Chemistry
%N 14
%P 6576--6581
%R 10.1021/jm300658n
%T Virtual Screening Identifies Novel Sulfonamide Inhibitors of ecto-5'-Nucleotidase
%U https://doi.org/10.1021%2Fjm300658n
%V 55

Picture credits