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8. Fosmidomycin as an Antimalarial Agent

Author

Wiesner, Jochen, Reichenberg, Armin, Hintz, Martin, Ortmann, Regina, Schlitzer, Martin, Van Calenbergh, Serge, Borrmann, Steffen, Lell, Bertrand, Kremsner, Peter G., Hutchinson, David, Jomaa, Hassan, Bach, Thomas J., editor, and Rohmer, Michel, editor

Published
2013
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14. Divergent strategy for the synthesis of [alpha]-aryl-substituted fosmidomycin analogues

Author

Deverux, Vincent, Wiesner, Jochen, Jomaa, Hassan, Rozenski, Jef, Van der Eycken, Johan, and Van Calenbergh, Serge

Subjects
Antimalarials -- Chemical properties, Antimalarials -- Structure, Phosphates -- Structure, Phosphates -- Chemical properties, Biological sciences, Chemistry
Abstract

A divergent strategy employed for the synthesis of [alpha]-aryl-substituted fosmidomycin analogues, which are often used as the antimalarial drugs are described. The methodology is found to exhibit a palladium-catalyzed Stille coupling as the key step, as the antimalarial activity of the analogues are clearly found to surpass that of the reference compound fosmidomycin.

Published
2007

18. Fosmidomycin as an Antimalarial Agent

Author

Wiesner, Jochen, primary, Reichenberg, Armin, additional, Hintz, Martin, additional, Ortmann, Regina, additional, Schlitzer, Martin, additional, Van Calenbergh, Serge, additional, Borrmann, Steffen, additional, Lell, Bertrand, additional, Kremsner, Peter G., additional, Hutchinson, David, additional, and Jomaa, Hassan, additional

Published
2012
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20. GcpE is involved in the 2-C-methyl-D-Erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli

Author

Altincicek, Boran, Kollas, Ann-Kristin, Sanderbrand, Silke, Wiesner, Jochen, Hintz, Martin, Beck, Ewald, and Jomaa, Hassan

Subjects
Microbial metabolism -- Genetic aspects, Escherichia coli -- Physiological aspects, Enzymes -- Structure-activity relationship, Protein engineering -- Research, Biological sciences
Abstract

Results reveal that gcpE gene of Escherichia coli plays a role in the mevalonate-independent 2-C-methyl 4-phosphate pathway of isoprenoid biosynthesis as shown by the ability of genetically engineered E. coli and those in which the gcpE gene is deleted to utilize exogenous mevalonate.

Published
2001

22. Profiling antimicrobial peptides from the medical maggot Lucilia sericata as potential antibiotics for MDR Gram-negative bacteria

Author

Hirsch, Rolf, Wiesner, Jochen, Marker, Alexander, Pfeifer, Yvonne, Bauer, Armin, Hammann, Peter E., Vilcinskas, Andreas, and Publica

Subjects
mice, Gram-negative bacteria, peptides, cytotoxicity, insecta, ddc:610, pharmacology, 610 Medizin und Gesundheit, pharmacokinetics, antibiotics, plasma, antimicrobials, toxic effect
Abstract

Background: The ability of MDR Gram-negative bacteria to evade even antibiotics of last resort is a severe global challenge. The development pipeline for conventional antibiotics cannot address this issue, but antimicrobial peptides (AMPs) offer an alternative solution. Objectives: Two insect-derived AMPs (LS-sarcotoxin and LS-stomoxyn) were profiled to assess their suitability for systemic application in humans. Methods: The peptides were tested against an extended panel of 114 clinical MDR Gram-negative bacterial isolates followed by time-kill analysis, interaction studies and assays to determine the likelihood of emerging resistance. In further in vitro studies we addressed cytotoxicity, cardiotoxicity and off-target interactions. In addition, an in vivo tolerability and pharmacokinetic study in mice was performed. Results: LS-sarcotoxin and LS-stomoxyn showed potent and selective activity against Gram-negative bacteria and no cross-resistance with carbapenems, fluoroquinolones or aminoglycosides. Peptide concentrations of 4 or 8 mg/L inhibited 90% of the clinical MDR isolates of Escherichia coli, Enterobacter cloacae, Acinetobacter baumannii and Salmonella enterica isolates tested. The 'all-D' homologues of the peptides displayed markedly reduced activity, indicating a chiral target. Pharmacological profiling revealed a good in vitro therapeutic index, no cytotoxicity or cardiotoxicity, an inconspicuous broad-panel off-target profile, and no acute toxicity in mice at 10 mg/kg. In mouse pharmacokinetic experiments LS-sarcotoxin and LS-stomoxyn plasma levels above the lower limit of quantification (1 and 0.25 mg/mL, respectively) were detected after 5 and 15 min, respectively. Conclusions: LS-sarcotoxin and LS-stomoxyn are suitable as lead candidates for the development of novel antibiotics; however, their pharmacokinetic properties need to be improved for systemic administration.

Published
2019

23. Differential stimulation of the Na+/H+ exchanger determines chloroquine uptake in Plasmodium falciparum

Author

Wunsch, Stefan, Sanchez, Cecilia P., Gekle, Michael, Grobe-Wortmann, Lars, Wiesner, Jochen, and Lanzer, Michael

Subjects
Plasmodium falciparum -- Genetic aspects, Cell research -- Genetic aspects, Chloroquine -- Physiological aspects, Antimalarials -- Physiological aspects, Biological sciences
Abstract

The human malarial parasite Plasmodium falciparum has become resistant to the antimalarial drug chloroquine, resulting in a dramatic increase in the incidence of malaria worldwide. An understanding of the parasite's biology could provide a basis for the development of new, improved antimalarial drugs. A new study identifies and characterizes a physiological marker linked to the chloroquine-resistant (CQR) Plasmodium falciparum. It is shown that CQR parasites constantly exhibit elevated cytoplasmic pH against that of chloroquine-sensitive strains. It is suggested that chloroquine activates the plasma membrane protein, Na+/H+ exchanger, involved in cell volume regulation and cytoplasmic pH.

Published
1998

38. Paramagnetic intermediates of (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (GcpE/IspG) under steady-state and pre-steady-state conditions

Author

Weiya Xu, Lees, Nicholas S., Adedeji, Dolapo, Wiesner, Jochen, Jomaa, Hassan, Hoffman, Brian M., and Duin, Evert C.

Subjects
Ring formation (Chemistry) -- Analysis, Electron paramagnetic resonance spectroscopy -- Usage, Enzyme binding -- Analysis, Hydroxides -- Chemical properties, Iron compounds -- Chemical properties, Iron compounds -- Magnetic properties, Methyl groups -- Structure, Methyl groups -- Chemical properties, Methyl groups -- Magnetic properties, Oxidation-reduction reaction -- Analysis, Phosphates -- Chemical properties, Chemistry
Abstract

(E)-4-Hydroxy-3-methylbut-2-enyl diphosphate synthase (GcpE/IspG) has converted 2-C-methyl-D-erythritol-2,4-cyclodiphosphate (MEcPP) into (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) in the penultimate step of the methyl-erythritol phosphate (MEP) pathway for isoprene biosynthesis. The EPR/ENDOR measurements have proposed a direct binding of the substrate to the [4Fe-4S] cluster during the reaction and have shown that the iron-sulfur cluster is involved in a reductive elimination of a hydroxyl group.

Published
2010

39. RlmN and Cfr are radical SAM enzymes involved in methylation of ribosomal RNA

Author

Feng Yan, Mankin, Alexander S., Fujimori, Danica Galonic, Rohrich, Rene, Wiesner, Jochen, Jomaa, Hassan, and LaMarre, Jacqueline M.

Subjects
Ribosomal RNA -- Analysis, Methylation -- Analysis, Iron compounds -- Electric properties, Iron compounds -- Chemical properties, Chemistry
Abstract

RlmN and Cfr are members of the Radical S-adenosylmethionine (SAM) superfamily, which are capable of accommodating the requisite [4Fe-4S] cluster. The analysis has represented the first in vitro description of the methyl transfer catalyzed by a member of the Radical SAM superfamily and they have implications for the functional consequences of Cfr-mediated modification of rRNA in the acquisition of antibiotic resistance.

Published
2010

40. Structure of (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, the terminal enzyme of the non-mevalonate pathway

Author

Rekittke, Ingo, Wiesner, Jochen, Rohrich, Rene, Demmer, Ulrike, Warkentin, Eberhard, Weiya Xu, Troschke, Kathrin, Hintz, Martin, Joo Hwan No, Duin, Evert C., Oldfield, Eric, Jomaa, Hassan, and Ermler, Ulrich

Subjects
Methyl groups -- Chemical properties, Oxidoreductases -- Chemical properties, Oxidoreductases -- Structure, Pyrophosphates -- Chemical properties, X-ray crystallography -- Usage, Chemistry
Abstract

The X-ray crystallographic structure of the enzyme (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) reductase, LytB, from Aquifex aeolicus and a structure-based model for catalysis are described. The results have shown that E126 is involved, with the ca. 5:1 isopentenyl diphosphate (IPP)/dimethylallyl diphosphate (DMAPP) product ratio being related to the E126 side-chain conformations, as there are no other candidates for protonating C4.

Published
2008

41. Synthesis of analogues of (E)-1-hydroxy-2-methylbut-2-enyl 4-diphosphate, an isoprenoid precursor and human [gamma][delta] T cell activator

Author

Van Hoof, Steven, Lacey, Carl Jeffrey, Rohrich, Rene C., Wiesner, Jochen, Jomaa, Hassan, and Calenbergh, Serge

Subjects
Pyrophosphates -- Chemical properties, T cell proliferation -- Research, Acylation -- Analysis, Biological sciences, Chemistry
Abstract

The analogues of (E)-1-hydroxy-2-methylbut-2-enyl 4-diphosphate (HMBPP) are synthesized, where the diphosphate group is replaced by isosteric moieties. The potential of the analogues to stimulate V[gamma]9/V[delta]2 T cell response or to inhibit GcpE and LytB, the last enzymes in the non-mevalonate pathway, is evaluated.

Published
2008

43. In Vitro Antimicrobial Efficacy of Tobramycin Against Staphylococcus aureus Biofilms in Combination With or Without DNase I and/or Dispersin B: A Preliminary Investigation

Author

Waryah, Charlene Babra, primary, Wells, Kelsi, additional, Ulluwishewa, Dulantha, additional, Chen-Tan, Nigel, additional, Gogoi-Tiwari, Jully, additional, Ravensdale, Joshua, additional, Costantino, Paul, additional, Gökçen, Anke, additional, Vilcinskas, Andreas, additional, Wiesner, Jochen, additional, and Mukkur, Trilochan, additional

Published
2017
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44. Fosmidomycin for malaria. (Research Letters)

Author

Missinou, Michel A, Borrmann, Steffen, Schindler, Andreas, Issifou, Saadou, Adegnika, Ayola A, Matsiegui, Pierre-Blaise, Binder, Ronald, Lell, Bertrand, Wiesner, Jochen, Baranek, Thomas, Jomaa, Hassan, and Kremsner, Peter G

Subjects
Malaria -- Drug therapy, Antimalarials -- Evaluation
Published
2002

46. FR-900098, an antimalarial development candidate that inhibits the non-mevalonate isoprenoid biosynthesis pathway, shows no evidence of acute toxicity and genotoxicity

Author

Wiesner, Jochen, primary, Ziemann, Christina, additional, Hintz, Martin, additional, Reichenberg, Armin, additional, Ortmann, Regina, additional, Schlitzer, Martin, additional, Fuhst, Rainer, additional, Timmesfeld, Nina, additional, Vilcinskas, Andreas, additional, and Jomaa, Hassan, additional

Published
2016
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49. Das Waldhuhn mit dem Goldhähnchengesang : Ost-West-Kooperation bei der Erforschung des Haselhuhns

Author

Klaus, Siegfried and Wiesner, Jochen

Subjects
ddc:590
Abstract

Die Geschichte einer über Jahrzehnte währenden Freundschaft und Ost-West-Kooperation wird am Beispiel der Haselhuhn-Forschung geschildert, bei der unserem Jubilar eine „Führungsrolle“ im besten Sinne zukam. Freilanduntersuchungen im polnischen Bialowieza und im Böhmerwald der damaligen Tschechoslowakei legten die Basis für zwei Neubearbeitungen der Haselhuhn – Monografie, erschienen in der Neuen Brehm-Bücherei des A. Ziemsen Verlags (1978, 1982), gefolgt von der um das Chinahaselhuhn Bonasa sewerzowi erweiterten Neuauflage 1996. Team work und produktive, immer erheiternde Arbeitstreffen in Jena konnten auch durch die innerdeutsche Grenze nicht verhindert werden. Detaillierte Verhaltensbeobachtungen an dem scheuen, versteckt lebenden Waldhuhn wurden erst durch den Durchbruch bei Haltung und Zucht in menschlicher Obhut möglich. Daraus folgte auch das in Deutschland erste und groß angelegte Wiederansiedlungsprojekt im Harz, dem zwar kein Langzeiterfolg beschieden war, dafür aber erheblichen Erkenntnisgewinn brachte. Ein neueres Vorhaben in Thüringer Frankenwald profitiert hoffentlich davon, indem es auf die Freilassung von Wildfängen setzt. During the last decades H.-H. Bergmann had a leading position in hazel grouse research – a cooperation project between East and West resulting in monographs of the species (Neue Brehm-Bücherei, A. Ziemsen Verlag 1978, 1982). During the difficult time of the “iron curtain” common field studies were carried out in the Bialowieza primeval forest (Poland) and in the Bohemian Forest (Czechia) and privat workshops were organized regularly in Jena/ eastern Germany. A 3rd edition (Bergmann et al. 1996) included the Chinese grouse Bonasa sewerzowi in addition to hazel grouse. Success in keeping and breeding hazel grouse in captivity offered the possibility of extended observations of behaviour and of a first releasing project in the Harz mountains, unfortunately without long-term success. As a consequence, a new releasing project in Frankenwald (Thuringia) is preferring wild caught birds instead of grouse from captivity.

Published
2011

50. Warum der Name 'Rauhfußkauz' 'rauh' bleiben sollte!

Author

Wiesner, Jochen

Subjects
ddc:590
Abstract

Die unlängst eingeführte Neuregelung der deutschen Rechtschreibung verfolgt unter anderem das Ziel, umständliche Schreibweisen durch einfachere Formen zu verkürzen, ohne dass sich der Sinngehalt der betreffenden Worte ändert. Sie beinhaltet aber auch gleichzeitig die Vorschrift, dass fest eingebürgerte Eigennamen ohne Rücksicht auf ihre Schreibweise nicht verändert werden dürfen. Dies trifft vor allem auf Orts-, Flur- und Personennamen zu, die schon seit langem so geschrieben werden. Der Rauhfußkauz wurde 1758 von Carl von Linné beschrieben und mit dem lateinischen Namen Strix funerea versehen.

Published
2011

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