Chemische Biologie

Auf der Suche nach neuen Therapien gegen Krankheitserreger setzen Wissenschaftler unter anderem auf chemische und biologische Wirkstoffe. Dies können Verbindungen sein, die als Antibiotikum wirken oder zur Stimulierung des Immunsystems dienen. Neue Wirkstoffe zu entdecken, ihre Funktionsweise zu charakterisieren und ihre Eigenschaften zu optimieren sind die drei Hauptziele der Abteilung „Chemische Biologie“ am HZI.




Fu, C., Keller, L., Bauer, A., Bronstrup, M., Froidbise, A., Hammann, P., Herrmann, J., Mondesert, G., Kurz, M., Schiell, M., Schummer, D., Toti, L., Wink, J. & Muller, R. Biosynthetic Studies of Telomycin Reveal New Lipopeptides with Enhanced Activity. J Am Chem Soc 137, 7692-705 (2015).

Halland, N., Bronstrup, M., Czech, J., Czechtizky, W., Evers, A., Follmann, M., Kohlmann, M., Schiell, M., Kurz, M., Schreuder, H.A. & Kallus, C. Novel Small Molecule Inhibitors of Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa) from Natural Product Anabaenopeptin. J Med Chem 58, 4839-44 (2015).

Herkommer, D., Dreisigacker, S., Sergeev, G., Sasse, F., Gohlke, H. & Menche, D. Design, synthesis, and biological evaluation of simplified side chain hybrids of the potent actin binding polyketides rhizopodin and bistramide. ChemMedChem 10, 470-89 (2015).

Hermane, J., Bulyszko, I., Eichner, S., Sasse, F., Collisi, W., Poso, A., Schax, E., Walter, J.G., Scheper, T., Kock, K., Herrmann, C., Aliuos, P., Reuter, G., Zeilinger, C. & Kirschning, A. New, non-quinone fluorogeldanamycin derivatives strongly inhibit Hsp90. Chembiochem 16, 302-11 (2015).

Hoffmann, H., Kogler, H., Heyse, W., Matter, H., Caspers, M., Schummer, D., Klemke-Jahn, C., Bauer, A., Penarier, G., Debussche, L. & Bronstrup, M. Discovery, Structure Elucidation, and Biological Characterization of Nannocystin A, a Macrocyclic Myxobacterial Metabolite with Potent Antiproliferative Properties. Angew Chem Int Ed Engl (2015).

Hu, H.Y., Lim, N.H., Ding-Pfennigdorff, D., Saas, J., Wendt, K.U., Ritzeler, O., Nagase, H., Plettenburg, O., Schultz, C. & Nazare, M. DOTAM derivatives as active cartilage-targeting drug carriers for the treatment of osteoarthritis. Bioconjug Chem 26, 383-8 (2015).

Kling, A., Lukat, P., Almeida, D.V., Bauer, A., Fontaine, E., Sordello, S., Zaburannyi, N., Herrmann, J., Wenzel, S.C., Konig, C., Ammerman, N.C., Barrio, M.B., Borchers, K., Bordon-Pallier, F., Bronstrup, M., Courtemanche, G., Gerlitz, M., Geslin, M., Hammann, P., Heinz, D.W., Hoffmann, H., Klieber, S., Kohlmann, M., Kurz, M., Lair, C., Matter, H., Nuermberger, E., Tyagi, S., Fraisse, L., Grosset, J.H., Lagrange, S. & Muller, R. Antibiotics. Targeting DnaN for tuberculosis therapy using novel griselimycins. Science 348, 1106-12 (2015).

Koutsoudakis, G., Romero-Brey, I., Berger, C., Perez-Vilaro, G., Perin, P.M., Vondran, F.W., Kalesse, M., Harmrolfs, K., Muller, R., Martinez, J.P., Pietschmann, T., Bartenschlager, R., Bronstrup, M., Meyerhans, A. & Diez, J. Soraphen A: a broad-spectrum antiviral natural product with potent anti-hepatitis C virus activity. J Hepatol (2015).

Martinez, J.P., Sasse, F., Bronstrup, M., Diez, J. & Meyerhans, A. Antiviral drug discovery: broad-spectrum drugs from nature. Nat Prod Rep 32, 29-48 (2015).

Naini, A., Muthukumar, Y., Raja, A., Franke, R., Harrier, I., Smith, A.B., 3rd, Lee, D., Taylor, R.E., Sasse, F. & Kalesse, M. The synthesis and biological evaluation of desepoxyisotedanolide and a comparison with desepoxytedanolide. Angew Chem Int Ed Engl 54, 6935-9 (2015).

Schulz, S., Eckweiler, D., Bielecka, A., Nicolai, T., Franke, R., Dotsch, A., Hornischer, K., Bruchmann, S., Duvel, J. & Haussler, S. Elucidation of sigma factor-associated networks in Pseudomonas aeruginosa reveals a modular architecture with limited and function-specific crosstalk. PLoS Pathog 11, e1004744 (2015).



Ahn S.B., M.A., Anand S., Cheruku H.R., Birch D., Sowmya G., Cantor D., Ranganathan S., Inglis D.W., Frank R., Agrez M., Nice E.C., Baker M.S. Characterization of the interaction between heterodimeric αvβ6 integrin and urokinase plasminogen activator receptor (uPAR) using functional proteomics. J Proteome Res 13, 5956-64 (2014).

Austel N., Bjorkman C., Hilker M., Meiners T. Phenotypic plasticity in host plant preference of the willow leaf beetle Phratora vulgatissima: The impact of experience made by adults. Agricultural and Forest Entomology 16, 417-25 (2014).

Bauer, A. & Bronstrup, M. Industrial natural product chemistry for drug discovery and development. Nat Prod Rep 31, 35-60 (2014).

Blanka, A., Schulz, S., Eckweiler, D., Franke, R., Bielecka, A., Nicolai, T., Casilag, F., Duvel, J., Abraham, W.R., Kaever, V. & Haussler, S. Identification of the alternative sigma factor SigX regulon and its implications for Pseudomonas aeruginosa pathogenicity. J Bacteriol 196, 345-56 (2014).

Buttler, K., Badar, M., Seiffart, V., Laggies, S., Gross, G., Wilting, J. & Weich, H.A. De novo hem- and lymphangiogenesis by endothelial progenitor and mesenchymal stem cells in immunocompetent mice. Cell Mol Life Sci 71, 1513-27 (2014).

Cui, S., Wienhoefer, N. & Bilitewski, U. Genistein induces morphology change and G2/M cell cycle arrest by inducing p38 MAPK activation in macrophages. Int Immunopharmacol 18, 142-50 (2014).

Fleta-Soriano, E., Martinez, J.P., Hinkelmann, B., Gerth, K., Washausen, P., Diez, J., Frank, R., Sasse, F. & Meyerhans, A. The myxobacterial metabolite ratjadone A inhibits HIV infection by blocking the Rev/CRM1-mediated nuclear export pathway. Microb Cell Fact 13, 17 (2014).

Fuchs, M., Kampfer, S., Helmsing, S., Spallek, R., Oehlmann, W., Prilop, W., Frank, R., Dubel, S., Singh, M. & Hust, M. Novel human recombinant antibodies against Mycobacterium tuberculosis antigen 85B. BMC Biotechnol 14, 68 (2014).

Harikrishna K., Mukkamala R., Hinkelmann B., Sasse F., Aidhen I.S. Iodine-promoted oxidative conversion of o-vinyl diaryl ketones into o-acetyl diaryl ketones, synthesis of 1-methyl-4-arylphthalazines as analogues of podophyllotoxin. European Journal of Organic Chemistry, 1066-75 (2014).

Harmrolfs, K., Mancuso, L., Drung, B., Sasse, F. & Kirschning, A. Preparation of new alkyne-modified ansamitocins by mutasynthesis. Beilstein J Org Chem 10, 535-43 (2014).

Hentschel F., Raimer B., Kelter G., Fiebig H.-H., Sasse F., Lindel T. . Synthesis and cytotoxicity of a diazirine-based photopsammaplin. European Journal of Organic Chemistry 2120-27 (2014).

Hotop, S.K., Abd El Wahed, A., Beutling, U., Jentsch, D., Motzkus, D., Frank, R., Hunsmann, G., Stahl-Hennig, C. & Fritz, H.J. Multiple antibody targets on herpes B glycoproteins B and D identified by screening sera of infected rhesus macaques with peptide microarrays. PLoS One 9, e86857 (2014).

Jerz, G., Elnakady, Y.A., Braun, A., Jackel, K., Sasse, F., Al Ghamdi, A.A., Omar, M.O. & Winterhalter, P. Preparative mass-spectrometry profiling of bioactive metabolites in Saudi-Arabian propolis fractionated by high-speed countercurrent chromatography and off-line atmospheric pressure chemical ionization mass-spectrometry injection. J Chromatogr A 1347, 17-29 (2014).

Kopf, T., Schaefer, H.L., Troetzmueller, M., Koefeler, H., Broenstrup, M., Konovalova, T. & Schmitz, G. Influence of fenofibrate treatment on triacylglycerides, diacylglycerides and fatty acids in fructose fed rats. PLoS One 9, e106849 (2014).

Lensing R., Behrens P., Müller P.P., Lenarz T., Stieve M. In vivo testing of a bioabsorbable magnesium alloy serving as total ossicular replacement prostheses. J Biomater Appl. 28, 688-96 (2014).

Lutz, V., Mannchen, F., Krebs, M., Park, N., Kruger, C., Raja, A., Sasse, F., Baro, A. & Laschat, S. SAR studies on hydropentalene derivatives-Important core units of biologically active tetramic acid macrolactams and ptychanolides. Bioorg Med Chem 22, 3252-61 (2014).

Maichrowski J., Bhasin. A., Sasse F., Kaufmann D.E. . Carbene-catalyzed aroylation of a 2-chloroquinoxaline n-oxide with aromatic aldehydes at room temperature. European Journal of Organic Chemistry 4457-60 (2014).

Mancuso, L., Knobloch, T., Buchholz, J., Hartwig, J., Moller, L., Seidel, K., Collisi, W., Sasse, F. & Kirschning, A. Preparation of thermocleavable conjugates based on ansamitocin and superparamagnetic nanostructured particles by a chemobiosynthetic approach. Chemistry 20, 17541-51 (2014).

Meiners, T., Stechmann, B. & Frank, R. EU-OPENSCREEN-chemical tools for the study of plant biology and resistance mechanisms. J Chem Biol 7, 113-8 (2014).

Muenzner J.K., B.B., Kalie H., Andronache I.C., Kaps L., Schuppan D., Sasse F., Schobert R. Gold(I) biscarbene complexes derived from vascular-disrupting combretastatin A-4 address different targets and show antimetastatic potential. ChemMedChem 9, 1195-1204 (2014).

Muller S., Sasse, F., Maier M.E. Synthesis of pladienolide b and its 7-epimer with insights into the role of the allylic acetate. European Journal of Organic Chemistry 1025-36 (2014).

Rahioui, I., Eyraud, V., Karaki, L., Sasse, F., Carre-Pierrat, M., Qin, A., Zheng, M.H., Toepfer, S., Sivignon, C., Royer, C., Da Silva, P. & Gressent, F. Host range of the potential biopesticide Pea Albumin 1b (PA1b) is limited to insects. Toxicon 89, 67-76 (2014).

Sergeev, G., Roy, S., Jarek, M., Zapolskii, V., Kaufmann, D.E., Nandy, R.K. & Tegge, W. High-throughput screening and whole genome sequencing identifies an antimicrobially active inhibitor of Vibrio cholerae. BMC Microbiol 14, 49 (2014).

Shaaban S., Sasse.F., Burkholz T., Jacob C. Sulfur, selenium and tellurium pseudopeptides: Synthesis and biological evaluation. Bioorganic and Medicinal Chemistry 22, 3610-19 (2014).

Waschke N., H.K., Hancock C., Hilker M., Obermaier E., Meiners T. Habitats as complex odour environments: How does plant diversity affect herbivore and parasitoid orientation? PLoS ONE 9, e85152 (2014).



Adla, S.K., Sasse, F., Kelter, G., Fiebig, H.H. & Lindel, T. Doubly prenylated tryptamines: cytotoxicity, antimicrobial activity and cyclisation to the marine natural product flustramine A. Org Biomol Chem 11, 6119-30 (2013).

Altendorfer, M., Raja, A., Sasse, F., Irschik, H. & Menche, D. Modular synthesis of polyene side chain analogues of the potent macrolide antibiotic etnangien by a flexible coupling strategy based on hetero-bis-metallated alkenes. Org Biomol Chem 11, 2116-39 (2013).

Ferir, G., Petrova, M.I., Andrei, G., Huskens, D., Hoorelbeke, B., Snoeck, R., Vanderleyden, J., Balzarini, J., Bartoschek, S., Bronstrup, M., Sussmuth, R.D. & Schols, D. The lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications. PLoS One 8, e64010 (2013).

Frei, R., Staedler, D., Raja, A., Franke, R., Sasse, F., Gerber-Lemaire, S. & Waser, J. Total synthesis and biological evaluation of jerantinine E. Angew Chem Int Ed Engl 52, 13373-6 (2013).

Irschik, H.W., Peter; Sasse,F.; Fohrer,J.; Huch,V.; Müller,R.; Prusov,E.V. Isolation, structure elucidation, and biological activity of maltepolides: remarkable macrolides from myxobacteria. Angewandte Chemie International Edition 52, 5402-5405 (2013).

Kempf, K., Raja, A., Sasse, F. & Schobert, R. Synthesis of penicillenol C1 and of a bis-azide analogue for photoaffinity labeling. J Org Chem 78, 2455-61 (2013).

Krawczyk, J.M., Voller, G.H., Krawczyk, B., Kretz, J., Bronstrup, M. & Sussmuth, R.D. Heterologous expression and engineering studies of labyrinthopeptins, class III lantibiotics from Actinomadura namibiensis. Chem Biol 20, 111-22 (2013).

Lu, H.H., Raja, A., Franke, R., Landsberg, D., Sasse, F. & Kalesse, M. Synthesis and biological evaluation of paleo-soraphens. Angew Chem Int Ed Engl 52, 13549-52 (2013).

Mancuso, L., Jurjens, G., Hermane, J., Harmrolfs, K., Eichner, S., Fohrer, J., Collisi, W., Sasse, F. & Kirschning, A. Bioreduction of aryl azides during mutasynthesis of new ansamitocins. Org Lett 15, 4442-5 (2013).

Munzner, J., Biersack, B., Kaps, L., Mahal, K., Schobert, R. & Sasse, F. Synergistic "gold effects" of anti-vascular 4,5-diarylimidazol-2-ylidene gold(I) carbene complexes. Int J Clin Pharmacol Ther 51, 44-6 (2013).

Muthukumar, Y., Roy, M., Raja, A., Taylor, R.E. & Sasse, F. The marine polyketide myriaporone 3/4 stalls translation by targeting the elongation phase. Chembiochem 14, 260-4 (2013).


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