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Latest publications

 

G. Jürjens, A. Kirschning:

Synthesis of a Cytotoxic Ansamycin Hybrid

Org. Lett. 2014, 16, 3000-3003.

chemabstractorglett2014g350.jpgThe synthesis of a new ansamycin macrolactam derivative that contains an ansa chain based on ansamitocin and an aromatic core related to geldanamycin is reported. The selective introduction of the cyclic carbamoyl group at C7 and C9 relies on a biotransformation using a mutant strain of S. hygroscopicus, the geldanamycin producer. The ansamycin hybrid forms atropisomers that differ in their antiproliferative activity toward cancer cells.

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S. Umayaparvathi, M. Arumugam, S. Meenakshi, G. Dräger, A. Kirschning, T. Balasubramanian :

Purification and Characterization of Antioxidant Peptides from Oyster ( Saccostrea cucullata ) Hydrolysate and the Anticancer Activity of Hydrolysate on Human Colon Cancer Cell Lines

Int. J. Pept. Res. Ther. 2014, 20, 231-243.

The focus of the study was to investigate antioxidant activity and characterize antioxidant peptides from oyster (Saccostrea cucullata) protein hydrolysate. The protease hydrolysate of oyster exhibited strong potential to donate hydrogen and was able to scavenge Hydrogen peroxide, Hydroxyl and DPPH radicals. Due to the high antioxidant potential, hydrolysate was purified in Sephadex G-25 gel filtration chromatography. The active peptide fraction was further purified by UPLC-MS. Totally seven antioxidant peptides were collected. Among seven peptides (SCAP 1–7), three peptides (SCAP 1, 3 and 7) had highest scavenging ability on DPPH radicals. The amino acid sequence and molecular mass of purified antioxidant peptides (SCAP1, SCAP3 and SCAP7) were determined by Q-TOF ESI mass spectroscopy and structures of the peptides were Leu-Ala-Asn-Ala-Lys (MW = 515.29 Da), Pro-Ser-Leu-Val-Gly-Arg-Pro–Pro-Val-Gly-Lys-Leu-Thr-Leu (MW = 1,432.89 Da) and Val-Lys-Val-Leu-Leu-Glu-His-Pro-Val-Leu (MW = 1,145.75 Da), respectively. The oyster hydrolysate was tested for cell cytotoxicity on Vero (kidney epithelial cells of the African Green Monkey) and HT-29 (human colon carcinoma) cell lines. It was found that the hydrolysate did not show any cytotoxic effect for Vero cell lines and exerted a significant cytotoxic effect on HT-29 cell lines. We thus conclude that the anticancer and antioxidative hydrolysate from oyster (S. cucullata) may be useful ingredients in food and nutraceutical applications.

 

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E. Schax, J.-G. Walter, H. Märzhäuser, F. Stahl, T. Scheper, D. A. Agard, S. Eichner, A. Kirschning, C. Zeilinger:

Microarray-Based Screening for Human and Bacterial Hsp90 Inhibitors

J. Biotechnol. 2014, 180, 1-9.

teaser-j-biochem-2014.jpgBased on the importance of heat shock proteins (HSPs) in diseases such as cancer, Alzheimer's disease or malaria, inhibitors of these chaperons are needed. Today's state-of-the-art techniques to identify HSP inhibitors are performed in microplate format, requiring large amounts of proteins and potential inhibitors. In contrast, we have developed a miniaturized protein microarray-based assay to identify novel inhibitors, allowing analysis with 300 pmol of protein. The assay is based on competitive binding of fluorescence-labeled ATP and potential inhibitors to the ATP-binding site of HSP. Therefore, the developed microarray enables the parallel analysis of different ATP-binding proteins on a single microarray. We have demonstrated the possibility of multiplexing by immobilizing full-length human HSP90α and HtpG of Helicobacter pylori on microarrays. Fluorescence-labeled ATP was competed by novel geldanamycin/reblastatin derivatives with IC50 values in the range of 0.5 nM to 4 μM and Z*-factors between 0.60 and 0.96. Our results demonstrate the potential of a target-oriented multiplexed protein microarray to identify novel inhibitors for different members of the HSP90 family.

 

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E. Geist, A. Kirschning, T. Schmidt:

sp 3-sp 3 Coupling reactions in the synthesis of natural products and biologically active molecules

Nat. Prod. Rep. 2014, 31, 441-448.

highlight-npr-graphabstr350.jpgThis Highlight covers the current status of relatively unexplored sp3–sp3 cross-coupling reactions with particular focus on natural product and related syntheses.

 

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K. Harmrolfs, L. Mancuso, B. Drung, F. Sasse, A. Kirschning:

Preparation of new alkyne-modified ansamitocins by mutasynthesis

Beilstein J. Org. Chem. 2014, 10, 535-543.

abstact-ansamytocyc-alkyen-graphabstr-revised350.jpgThe preparation of alkyne-modified ansamitocins by mutasynthetic supplemen-tation of Actinosynnema pretiosum mutants with alkyne-substituted amino-benzoic acids is described. This modification paved the way to introduce a thiol linker by Huisgen-type cyclo addition which can principally be utilized to create tumor targeting conjugates. In bioactivity tests, only those new ansami- tocin derivatives showed strong antiproliferative activity that bear an ester side chain at C-3.

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A. Weber, R. Dehn, N. Schläger, B. Dieter, A. Kirschning:

Total Synthesis of the Antibiotic Elansolid B1

Org. Lett. 2014, 16, 568-571.

elansolid-abstract-350-px.jpgThe antibiotic elansolid B1 was prepared by a convergent strategy that relied on a highly diastereoselective, biomi- metic intramolecular Diels − Alder cycloaddition (IMDA) that furnished the tetrahydroindane unit. Other key features are a double Sonogashira cross-coupling and a substrate- controlled Yamamoto aldol reaction.

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