A5004558056- Microbial Natural Products and Biosynthesis
- Chemical Synthesis and Reactions
- Chemical Synthesis and Analysis
- Inorganic and Organometallic Chemistry
- Carbohydrate Chemistry and Synthesis
- Oxidative Organic Chemistry Reactions
- Radical Photochemical Reactions
- Molecular spectroscopy and chirality
- Receptor Mechanisms and Signaling
- Marine Sponges and Natural Products
- Genomics and Phylogenetic Studies
- Cancer therapeutics and mechanisms
- RNA and protein synthesis mechanisms
- Analytical Chemistry and Chromatography
- Neuropeptides and Animal Physiology
- Diabetes Treatment and Management
- DNA and Nucleic Acid Chemistry
- Glycosylation and Glycoproteins Research
- Photochemistry and Electron Transfer Studies
- X-ray Diffraction in Crystallography
- Chemical Reactions and Isotopes
- Catalysis and Oxidation Reactions
- Crystallization and Solubility Studies
- Biochemical and Structural Characterization
- Fluorine in Organic Chemistry
Philipps University of Marburg
2020-2025
Sanofi (Germany)
2016-2025
Munich University of Applied Sciences
2025
Sanofi (France)
2022
Bavarian Nordic (United States)
2015
Smiths Detection (France)
2015
Institut National de la Recherche Scientifique
2002
University of Münster
2000
Gesundes Kinzigtal (Germany)
1998
Illinois State University
1988-1996
The discovery of Streptomyces-produced streptomycin founded the age tuberculosis therapy. Despite subsequent development a curative regimen for this disease, remains worldwide problem, and emergence multidrug-resistant Mycobacterium has prioritized need new drugs. Here we show that optimized derivatives from Streptomyces-derived griselimycin are highly active against M. tuberculosis, both in vitro vivo, by inhibiting DNA polymerase sliding clamp DnaN. We discovered resistance to...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotochemistry of carbocyanine alkyltriphenylborate salts: intra-ion-pair electron transfer and the chemistry boranyl radicalsSubhanakar Chatterjee, Paul D. Davis, Peter Gottschalk, Michael E. Kurz, Bjorn Sauerwein, Xiqiang Yang, Gary B. SchusterCite this: J. Am. Chem. Soc. 1990, 112, 17, 6329–6338Publication Date (Print):August 1, 1990Publication History Published online1 May 2002Published inissue 1 August...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIron(III)-ethylenediaminetetraacetic acid-peroxide systemCheves Walling, Michael Kurz, and Harvey J. SchugarCite this: Inorg. Chem. 1970, 9, 4, 931–937Publication Date (Print):April 1, 1970Publication History Published online1 May 2002Published inissue 1 April 1970https://pubs.acs.org/doi/10.1021/ic50086a048https://doi.org/10.1021/ic50086a048research-articleACS PublicationsRequest reuse permissionsArticle Views526Altmetric-Citations94LEARN ABOUT...
Dual activation of the glucagon-like peptide 1 (GLP-1) and glucagon receptor has potential to lead a novel therapy principle for treatment diabesity. Here, we report series peptides with dual activity on these receptors that were discovered by rational design. On basis sequence analysis structure-based design, structural elements engineered into selective GLP-1 agonist exendin-4, resulting in hybrid potent GLP-1/glucagon activity. Detailed structure-activity relationship data are shown....
The vasoactive cyclic 11-amino acid peptide urotensin II (U-II) has recently been discovered as the endogenous ligand of orphan G-protein-coupled receptor GPR14. As U-II might be involved in regulation cardiovascular homeostasis and pathology, a nonpeptidic GPR14/U-II antagonist is considerable basic therapeutic interest. We have performed structure-activity relationship studies on by investigating 25 analogues to mobilize intracellular calcium GPR14-transfected CHO cells, demonstrating that...
Exceptionally high accuracy and detection limits characterize the NMR experiment, a variant of TOSCY (TOSCY = Total Correlation Spectroscopy), described here for determination heteronuclear 3 J couplings. No enrichment heteroatom is necessary. The process, which also yields coupling constants smaller than signal width, only applicable to proton‐bearing heteroatoms. In addition, protons linked by transfer should belong same spin system. Application in angle ϕ peptides demonstrates performance process.
Abstract The structure of the fabclavines—unique mixtures nonribosomally derived peptide–polyketide hybrids connected to an unusual polyamino moiety—has been solved by detailed NMR and MS methods. These compounds have identified in two different entomopathogenic Xenorhabdus strains, thereby leading also identification fabclavine biosynthesis gene cluster. Detailed analysis these clusters initial mutagenesis experiments allowed prediction a pathway which moiety is from type fatty acid...
Telomycin (TEM) is a cyclic depsipeptide antibiotic active against Gram-positive bacteria. In this study, five new natural telomycin analogues produced by Streptomyces canus ATCC 12646 were identified. To understand the biosynthetic machinery of and to generate more pathway engineering, TEM biosynthesis gene cluster has been characterized from S. 12646: it spans approximately 80.5 kb consists 34 genes encoding fatty acid ligase, nonribosomal peptide synthetases (NRPSs), regulators,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPeptide flexibility and calculations of an ensemble moleculesDale F. Mierke, Michael Kurz, Horst KesslerCite this: J. Am. Chem. Soc. 1994, 116, 3, 1042–1049Publication Date (Print):February 1, 1994Publication History Published online1 May 2002Published inissue 1 February 1994https://pubs.acs.org/doi/10.1021/ja00082a027https://doi.org/10.1021/ja00082a027research-articleACS PublicationsRequest reuse permissionsArticle...
Abstract During the search for novel natural products from entomopathogenic Xenorhabdus doucetiae DSM17909 and X. mauleonii DSM17908 peptides named xenoamicins were identified in addition to already known antibiotics xenocoumacin xenorhabdin. Xenoamicins are acylated tridecadepsipeptides consisting of mainly hydrophobic amino acids. The main derivative xenoamicin A ( 1 ) was isolated DSM17908, its structure elucidated by detailed D 2 NMR experiments. Detailed MS experiments, also combination...
With progress in genome sequencing and data sharing, 1,000s of bacterial genomes are publicly available. Genome mining-using bioinformatics tools terms biosynthetic gene cluster (BGC) identification, analysis, rating-has become a key technology to explore the capabilities for natural product (NP) biosynthesis. Comprehensively, analyzing genetic potential phylum Bacteroidetes revealed Chitinophaga as most talented genus BGC abundance diversity. Guided by computational predictions, we...
Abstract To investigate the role of proline in defining β turn conformations within cyclic hexa‐ and pentapeptides we synthesized determined a series L ‐ D ‐proline‐containing peptides by means 2D NMR spectroscopy restrained molecular dynamics simulations. Due to cis / trans isomerism ‐proline adopt at least two different that are analyzed compared structures corresponding peptides. The compounds cyclo (‐Pro‐Ala‐Ala‐Pro‐Ala‐Ala‐), (‐Arg‐Gly‐Asp‐Phe‐Pro‐Gly‐), (‐Arg‐Gly‐Asp‐Phe‐Pro‐Ala‐),...
Abstract In an antibiotic lead discovery program, the known strain Streptomyces armeniacus DSM19369 has been found to produce three new natural products when cultivated on a malt‐containing medium. The challenging structural elucidation of isolated compounds was achieved by using independent methods, that is, chemical degradation followed NMR spectroscopy, computer‐assisted structure prediction algorithm, and X‐ray crystallography. compounds, named armeniaspirol A–C ( 2 – 4 ), exhibit...
Abstract The bengamides, sponge‐derived natural products that have been characterized as inhibitors of methionine aminopeptidases (MetAPs), intensively investigated anticancer compounds. We embarked on a multidisciplinary project to supply bengamides by fermentation the terrestrial myxobacterium M. virescens, decipher their biosynthesis, and optimize properties drug leads. characterization biosynthetic pathway revealed bacterial resistance is conferred Leu 154 myxobacterial MetAP protein,...
Abstract Mature thrombin activatable fibrinolysis inhibitor (TAFIa) is a carboxypeptidase that stabilizes fibrin clots by removing C-terminal arginines and lysines from partially degraded fibrin. Inhibition of TAFIa stimulates the degradation may help to prevent thrombosis. Applying lead finding approach based on literature-mining, we discovered anabaenopeptins, cyclic peptides produced cyanobacteria, were potent inhibitors with IC 50 values as low 1.5 nM. We describe isolation structure...
Novel peptidic dual agonists of the glucagon-like peptide 1 (GLP-1) and glucagon receptor are reported to have enhanced efficacy over pure GLP-1 with regard treatment obesity diabetes. We describe novel exendin-4 based designed an activity ratio favoring versus receptor. As result iterative optimization procedure that included molecular modeling, structural biological studies (X-ray, NMR), design synthesis, experimental activity, solubility profiling, a candidate molecule was identified. SAR...
Urotensin II (U-II; cyclo5-10[H-Glu-Thr-Pro-Asp-Cys-Phe-Trp-Lys-Tyr-Cys-Val-OH]) is a potent vasoconstrictor in mammals, and it postulated that plays central role cardiovascular homeostasis. Thus, we initiated structure-to-function analysis of this peptide characterized by N-terminal tail cyclic core formed through disulfide bridging. A total 41 analogs focusing on these characteristics were developed evaluated using binding assay membranes from stable HEK-293 cell line containing the human...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAromatic hydroxylation with hydrogen peroxide-aluminum chlorideMichael E. Kurz and Glen J. JohnsonCite this: Org. Chem. 1971, 36, 21, 3184–3187Publication Date (Print):October 1, 1971Publication History Published online1 May 2002Published inissue 1 October 1971https://pubs.acs.org/doi/10.1021/jo00820a023https://doi.org/10.1021/jo00820a023research-articleACS PublicationsRequest reuse permissionsArticle Views460Altmetric-Citations46LEARN ABOUT THESE...
A new class of four depsipentapeptides called chaiyaphumines A–D (1–4) was isolated from Xenorhabdus sp. PB61.4. Their structures were elucidated by detailed 1D and 2D NMR experiments a Marfey's analysis following flash hydrolysis the peptide. Verification structure achieved three-dimensional modeling using NOE-derived distance constraints, molecular dynamics, energy minimization. Chaiyaphumine (1) showed good activity against Plasmodium falciparum (IC50 0.61 μM), causative agent malaria,...
A new hexadepsipeptide called xenobactin (1) was isolated from Xenorhabdus sp. PB30.3. Structure elucidation performed after isolation by extensive 1D- and 2D-NMR experiments. To determine the absolute configuration of amino acids, modifications advanced Marfey's method were applied avoiding racemization additionally allowing stereochemical assignment tryptophan. Moreover, three dimensional structure modeled ROE derived constraints molecular dynamics runs. The major conformation verified...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReactions of Peroxides with Halide Salts. Electrophilic and Homolytic HalogenationsJay K. Kochi, Bruce M. Graybill, Michael. KurzCite this: J. Am. Chem. Soc. 1964, 86, 23, 5257–5264Publication Date (Print):December 1, 1964Publication History Published online1 May 2002Published inissue 1 December 1964https://pubs.acs.org/doi/10.1021/ja01077a043https://doi.org/10.1021/ja01077a043research-articleACS PublicationsRequest reuse permissionsArticle...