Institute of Toxicology and Genetics

Karlsruhe, Germany

Institute of Toxicology and Genetics

Karlsruhe, Germany
SEARCH FILTERS
Time filter
Source Type

News Article | May 12, 2017
Site: phys.org

Treatment methods can now be adapted better to the individual needs of patients. Scientists at KIT have found a way to execute so-called high-throughput screenings with thousands of samples tested in parallel without any expensive, complex robotic systems that have been necessary so far. Chemist Pavel Levkin of KIT's Institute of Toxicology and Genetics (ITG) and his multidisciplinary team have developed a surface on which aqueous solutions self-arrange in thousands of separate droplets. "On a droplet microarray (DMA), biological samples such as tissue from a biopsy can be subjected to substance screening," says team member Simon Widmaier. Every individual droplet is used as a test tube for biological experiments. Pipetting robots and pipette tips used today are no longer required. "An individual laboratory employee can execute thousands of substance screening experiments within a few seconds." The cost reduction potential of this new technology is enormous, according to Widmaier. "A pipetting robot costs several 10,000 euros and has to be operated by an expert." Each pipetting step alone costs five to seven cents for a pipette tip. By means of a highly precise UV exposure method, highly hydrophilic and highly water-repellent areas are produced on the array surface. As a result, the size of the droplets to be investigated can vary between three and 250 nanoliters (one nanoliter corresponds to one billionth of a liter). When using conventional microtiter plates with lines and rows of depressions, at least 40 microliters (one millionth of a liter) of reactants are required. "Estimated roughly, a DMA consumes a thousand times less reactant. As these substances often are very expensive—some are more expensive than gold—this is a big advantage for users," Widmaier says. Moreover, classical pipetting technology does not allow for portioning fluids with finely dispersed solids, e.g. cells, in nanoliter amounts. On the novel biologically compatible polymer, by contrast, experiments are possible using a few living cells. The technology has big advantages when screening stem and primary cells for the effect of substances on human organs. Widmaier expects that screening results will be more reliable and development of medicine will be much cheaper in the future. The researchers also want to make it easier for diagnostic laboratories to perform personalized substance screenings for e.g. cancer treatment. Last, but not least, costs of large pharmaceutical companies will be reduced. "The DMA technology solves the central problem of miniaturization of cell experiments and allows for screenings of medical substances and smallest cell volumes, an example being biopsy tissues of patients. We want to develop, produce, and commercialize droplet microarrays, product platforms, and screening kits, and offer them to research institutes, screening centers, and pharmaceutical companies for cell-based substance screening in the context of personalized medicine," Widmayer says. First prototypes are being tested on the market. Explore further: CRISPR meets single-cell sequencing in new screening method


News Article | May 12, 2017
Site: www.eurekalert.org

Treatment methods can be adapted better to the individual needs of patients. The scientists of KIT have found a way to execute so-called high-throughput screenings with thousands of samples being tested in parallel without any expensive and complex robot systems that have been necessary so far. Chemist Pavel Levkin of KIT's Institute of Toxicology and Genetics (ITG) and his multidisciplinary team have developed a surface on which aqueous solutions self-arrange in thousands of separate droplets. "On a droplet microarray (DMA), biological samples, such as tissue from a biopsy, can be subjected to substance screening," Levkin's team member Simon Widmaier, ITG, says. Every individual droplet is used as a type of test tube for biological experiments. Pipetting robots and pipette tips that have been indispensable so far are no longer required. "An individual laboratory employee can execute thousands of substance screening experiments within a few seconds." The cost reduction potential of this new technology is enormous according to Widmaier. "A pipetting robot costs several 10,000 Euros and has to be operated by an expert." Each pipetting step alone costs five to seven cents for a pipette tip. By means of a highly precise UV exposure method, highly water-attracting and highly water-repellent areas are produced on the array surface. As a result, the size of the droplets to be investigated can be varied between three and 250 nanoliters (one nanoliter corresponds to one billionth of a liter). When using conventional microtiter plates with lines and rows of depressions, 40 microliters (one microliter corresponds to one millionth of a liter) of reactants at least are required. "Estimated roughly, a DMA consumes a thousand times less reactants. As these substances often are very expensive - some are more expensive than gold - this is a big advantage for users," Widmaier says. Moreover, classical pipetting technology does not allow for portioning fluids with finely dispersed solids, e.g. cells, in nanoliter amounts. On the novel biologically compatible polymer, by contrast, experiments can also be performed with a few living cells. The technology has big advantages when screening stem and primary cells for the effect of substances on human organs. Widmaier expects that screening results will be more reliable and development of medicine will be much cheaper in the future. To commercialize their findings, the researchers plan to establish the company Aquarray. In this way, they want to enable biological research laboratories with small funds to perform high-throughput screenings. They also want to make it easier for diagnostic laboratories to perform personalized substance screenings for e.g. cancer treatment. Last, but not least, costs of large pharmaceutical companies will be reduced. "The DMA technology solves the central problem of miniaturization of cell experiments and allows for screenings of medical substances and smallest cell volumes, an example being biopsy tissues of patients. We want to develop, produce, and commercialize droplet microarrays, product platforms, and screening kits and offer them to research institutes, screening centers, and pharmaceutical companies for cell-based substance screening in the context of personalized medicine," Widmayer says. First prototypes are being tested on the market. Karlsruhe Institute of Technology (KIT) pools its three core tasks of research, higher education, and innovation in a mission. With about 9,300 employees and 25,000 students, KIT is one of the big institutions of research and higher education in natural sciences and engineering in Europe.


Lindner S.,John Innes Center | Lindner S.,Karlsruhe Institute of Technology | Geu-Flores F.,Karlsruhe Institute of Technology | Brase S.,Karlsruhe Institute of Technology | And 3 more authors.
Chemistry and Biology | Year: 2014

The core structure of the iridoid monoterpenes is formed by a unique cyclization reaction. The enzyme that catalyzes this reaction, iridoid synthase, is mechanistically distinct from other terpene cyclases. Here we describe the synthesis of two substrate analogs to probe the mechanism of iridoid synthase. Enzymatic assay of these substrate analogs along with clues from the product profile of the native substrate strongly suggest that iridoid synthase utilizes a Michael reaction to achieve cyclization. This improved mechanistic understanding will facilitate the exploitation of the potential of iridoid synthase to synthesize new cyclic compounds from nonnatural substrates. © 2014 Elsevier Ltd. All rights reserved.


Hagendorn T.,Karlsruhe Institute of Technology | Brase S.,Karlsruhe Institute of Technology | Brase S.,Institute of Toxicology and Genetics
RSC Advances | Year: 2014

The current paper describes a new synthesis of heteroatom-substituted cyclooctynes. By using the Nicholas reaction we managed to design a concise synthesis that only uses three steps to build the eight-membered ring. It was also possible to functionalize said alkyne with a fluorophore. This journal is © the Partner Organisations 2014.


Seifermann S.M.,Karlsruhe Institute of Technology | Muller T.,Karlsruhe Institute of Technology | Brase S.,Karlsruhe Institute of Technology | Brase S.,Institute of Toxicology and Genetics
European Journal of Organic Chemistry | Year: 2013

The synthesis of four new bis(oxazoline) (BOX) derivatives bearing two additional coordination sites at the 4,4′-positions is presented. As these BOX scaffolds contain an unsubstituted methylene bridge, they should be capable of forming neutral metal complexes. Thus, these molecules are very interesting ligands for bifunctional catalysis. In addition, one BOX scaffold bearing two azide moieties was successfully employed in copper-free 1,3-dipolar cycloaddition reactions. The resulting products have yet again high ligand potential. The efficient synthesis of bis(oxazoline) (BOX) derivatives bearing two additional coordination sites at the 4,4′-positions is presented. As these BOX scaffolds contain an unsubstituted methylene bridge, they should be capable of forming neutral metal complexes. Thus, these molecules are very interesting ligands for bifunctional catalysis. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Hafner A.,Karlsruhe Institute of Technology | Fischer T.S.,Karlsruhe Institute of Technology | Brase S.,Karlsruhe Institute of Technology | Brase S.,Institute of Toxicology and Genetics
European Journal of Organic Chemistry | Year: 2013

A modified Julia-Kocienski protocol was investigated for the synthesis of CF3-substituted terminal olefins. By employing a simple one-step procedure, aldehydes were converted into the corresponding CF 3-substituted olefins using 2-[(2,2,2-trifluoroethyl)sulfonyl] benzo[d]thiazole as the trifluoromethylation agent. This sulfone was prepared on a gram scale in two steps from inexpensive and commercially available trifluoroethanol. The Julia-Kocienski olefination tolerated various functional groups, and the trifluoromethylated olefins were obtained in good yields. However, the E/Z selectivity was strongly substrate dependent, and only moderate selectivities could be achieved. By employing a two-step procedure, it was possible to synthesize an α-trifluoromethyl-substituted sulfone on a gram scale by starting from inexpensive and commercially available trifluoroethanol. This substrate could then be used in a modified Julia-Kocienski olefination to prepare trifluoromethyl-substituted terminal olefins). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Hagendorn T.,Karlsruhe Institute of Technology | Brase S.,Karlsruhe Institute of Technology | Brase S.,Institute of Toxicology and Genetics
European Journal of Organic Chemistry | Year: 2014

A new silver-free synthesis for cyclooctynol is introduced. The obtained alcohol was further functionalized by a Mitsunobu reaction to give an assortment of imide and phenol derivatives. It was also possible to further functionalize the cyclooctyne by treatment with a fluorescein dye. As an interesting application, we used a cyclooctyne-maleimide conjugate as an azide-thiol crosslinker. A new synthesis for cyclooct-2-ynol is presented that does not employ silver salts. The obtained alcohol was further functionalized by Mitsunobu chemistry to afford new cyclooctynes. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Monnereau L.,Fritz Haber Institute | Nieger M.,University of Helsinki | Muller T.,Fritz Haber Institute | Brase S.,Fritz Haber Institute | Brase S.,Institute of Toxicology and Genetics
Advanced Functional Materials | Year: 2014

The efficient syntheses of tetrakis(thiophenol)methane and of a new poly(disulfide) hyper-crosslinked polymer based on the former monomer are described. Controlled de-polymerization as well as surface post- functionalization are successfully conducted on this novel material. Direct prove of post-functionalization is obtained through solid-state fluorescence emission spectroscopy, and the number of unreacted thiol-functions on the surface of the polymeric material is indirectly quantified by de-polymerization of the post-functionalized material. The efficient generation of a hyper-crosslinked poly(disulfide) is described. After high yielding synthesis of the monomer tetrakis-(4-thiylphenyl)methane, the polymeric material is obtained in excellent yield under mild reaction conditions. Combination of controlled de-polymerization under bio-compatible conditions and postfunctionalization gives access to the number of free termini at the surface. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Muller T.,The Innovation Group | Brase S.,Fritz Haber Institute | Brase S.,Institute of Toxicology and Genetics
RSC Advances | Year: 2014

The preference of material chemists for specific organic building blocks for the generation of porous crystalline or amorphous covalently linked materials or supramolecular architectures, held together by hydrogen bonding or metal coordination, is reviewed. Tetrakisphenylmethane and adamantane cores are readily to hand and easily endowed with various functional groups suitable for network generation. Besides, these structures fulfil the stiffness requirements in order to generate permanently porous frameworks. By reviewing the major types of porous networks through selected examples, the authors intend to give a concise overview to the specialist in the field and to provide the non-specialist with a tool box of possibilities. © The Royal Society of Chemistry 2014.


Hafner A.,Fritz Haber Institute | Jung N.,Institute of Toxicology and Genetics | Brase S.,Fritz Haber Institute | Brase S.,Institute of Toxicology and Genetics
Synthesis (Germany) | Year: 2014

Direct perfluoroalkylation reactions, especially trifluoromethylations of organic substrates, are of particular importance in modern organic chemistry as they allow rapid access to perfluoroalkylated molecules. In contrast to common metal-mediated perfluoroalkylations, recently developed silver-mediated perfluoroalkylation protocols offer the opportunity for orthogonal introduction of fluorine containing groups in organic compounds. This review gathers recent progress on silver-mediated perfluoroalkylation reactions and gives an overview over efficient syntheses, properties, and reactivity of perfluoroorganosilver(I) compounds. In addition, cooperative effects with copper-mediated processes are discussed. 1 Introduction 2 Syntheses and Properties of Perfluoroorganosilver Compounds 3 Silver-Mediated Perfluoroalkylations 3.1 Perfluoroorganosilver Compounds in Copper-Mediated Perfluoroalkylations 3.2 Perfluoroorganosilver Compounds as Precursors for Radicals 3.3 Perfluoroorganosilver Compounds as Nucleophilic Reagents 3.4 Silver-Catalyzed Perfluoroalkylations 4 Conclusion and Outlook. ©Georg Thieme Verlag Stuttgart New York.

Loading Institute of Toxicology and Genetics collaborators
Loading Institute of Toxicology and Genetics collaborators