Faculty of Chemistry

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Recent Publications

by Clemens Richert, Dejana Jovanovic, Peter Tremmel, S., Pradeep Pallan and Martin Egli

Angew. Chem. Int. Ed.
DOI: 10.1002/anie.202008665

For further information please contact:
Prof. Clemens Richert
Institute of Organic Chemistry
University of Stuttgart

 

In the course of the evolution of higher organisms such as mammals, gene duplication often occurs. The resulting "twin genes" have a very similar genetic makeup, but are independent of each other and can therefore specialize in certain tasks. An example of this is DNA methylation, a chemical change in the basic building blocks of the genetic material of a cell, which is caused by the transfer of methyl groups by enzymes (DNA methyl transferases, DNMT) to certain locations in the DNA. The DNA-methyltransferases DNMT3A and DNMT3B are two forms of these enzymes in human cells that have arisen from gene duplication.

Over 20 years ago, it was discovered that DNMT3B is essential for the DNA methylation of certain regions in the human genome and that insufficient activity of DNMT3B leads to the so-called ICF syndrome. However, why DNMT3B is specifically required for this task and why, for example, the twin DNMT3A cannot take over this task has so far remained unknown.

DNMT3B is required for the methylation of certain sequences in human chromosomes (orange). The specificity of DNMT3B for these regions is determined by a specific protein loop around Arginine 823 (gray). Figure: University of Stuttgart / IBTB.

In cooperation with groups from the University of California and the University of North Carolina at Chapel Hill, the team of Prof. Jeltsch has now been able to solve the structure of DNMT3B in complex with other DNA sequences and measure the turnover rate of DNA methylation by DNMT3B and DNMT3A on thousands of DNA sequences. It was shown that DNMT3B is particularly active on its target sequences in the human genome due to a special protein loop, while DNMT3A can only work poorly on these sequences.

Authors: Linfeng Gao, Max Emperle, Yiran Guo, Sara A. Grimm, Wendan Ren, Sabrina Adam, Hidetaka Uryu, Zhi-Min Zhang, Dongliang Chen, Jiekai Yin, Michael Dukatz, Hiwot Anteneh, Renata Z. Jurkowska, Jiuwei Lu, Yinsheng Wang, Pavel Bashtrykov, Paul A. Wade, Gang Greg Wang, Albert Jeltsch & Jikui Song
Nature Communications volume 11, Article number: 3355 (2020)

For further information please contact
Prof. Albert Jeltsch
Institute of Biochemistry and Technical Biochemistry, Dept. of Biochemistry
University of Stuttgart

by S. Bette, J. Stelzner, G. Eggert, Th. Schleid, G. Matve'eva, U. Kolb,
R. E. Dinnebier
Angew. Chem. Int. Ed. 59, 9438 (2020)
DOI: 10.1002/anie.202001609

For further information please contact:
Prof. Thomas Schleid
Institute of Inorganic Chemistry
University of Stuttgart

by Avijit Maiti, Jessica Stubbe, Dr. Nicolás I. Neuman, Dr. Pankaj Kalita, Prakash Duari, Prof. Dr. Carola Schulzke, Prof. Dr. Vadapalli Chandrasekhar,
Prof. Dr. Biprajit Sarkar, Dr. Anukul Jana

Angew. Chem. Int. Ed. 2020, 59, 6729 –6734
DOI: 10.1002/anie.201915802

For further information please contact:
Prof. Biprajit Sarkar
Institute of Inorganic Chemistry
University of Stuttgart

by Dr. Debdeep Mandal, Shubhadeep Chandra, Dr. Nicolás I. Neuman, Alok Mahata, Arighna Sarkar, Dr. Abhinanda Kundu, Dr. Srinivas Anga, Hemant Rawat, Prof. Dr. Carola Schulzke, Dr. Kaustubh R. Mote, Prof. Dr. Biprajit Sarkar,
Prof. Vadapalli Chandrasekhar, Dr. Anukul Jana

Chem. Eur. J.2020, 26, 5951 –5955
DOI: 10.1002/chem.202000276

For further information please contact:
Prof. Biprajit Sarkar
Institute of Inorganic Chemistry
University of Stuttgart

by Yingya Yang, Jannik Brückmann, Dr. Wolfgang Frey, Prof. Dr. Sven Rau,
Dr. Michael Karnahl and Dr. Stefanie Tschierlei

Chem. Eur. J. 2020,
DOI 10.1002/chem.202001564

For further information please contact:
Dr. Michael Karnahl
Institute of Organic Chemistry
University of Stuttgart

by Till Opatz, Joerg Senn-Bilfinger and Clemens Richert

Angew. Chem. Int. Ed. 2020
10.1002/anie.202004721

For further information please contact
Prof. Clemens Richert
Institute of Organic Chemistry
University of Stuttgart

 

Cyclopropenium cations are aromatic three-membered rings and belong to Hückel type aromatic systems. Thus, they are the smaller brothers of the well-known benzene. In contrast to benzene cyclopropenium cations were considered for a long time as curiosities without any practical relevance. However, in recent years their potential as organocatalysts has been recognized. Furthermore, polyelectrolytes carrying aminocyclopropenium subunits have been demonstrated as promising battery materials. However, there was a missing link, i.e. low molecular aminocyclopropenium-based compounds connecting features of organocatalysts and polyelectrolytes.   

Recently, an international team from the University of Stuttgart, the Columbia University in New York, the Cornell University in Ittaca and the Colorado State University in Fort Collins successfully realized the synthesis and characterization of liquid crystalline aminocyclopropenium salts. These deltic ionic liquid crystals possess a cationic head group and long hydrophobic side chains. These aminocyclopropenium salts self-assemble due to the nano-segregation of immiscible molecular parts of different polarity into columnar or lamellar structures, so-called mesophases. These mesophases can be characterized via polarizing optical microscopy, differential scanning calorimetry and X-ray diffraction thermally and structurally and serve as models for the above mentioned polyelectrolytes. The results are reported in a VIP research article in the journal Angewandte Chemie International Edition (doi.org/10.1002/anie.202000824).

Angew. Chem. int. Ed.
DOI: 10.1002/anie.202000824

For further information please contact:
Prof. Sabine Laschat
Institute of Organic Chemistry
University of Stuttgart
Jeffrey S. Bandar, Colorado State University, Fort Collins/CO, U.S.A.
Tristan H. Lambert, Cornell University, Ittaca/NY, U.S.A.,
Columbia University, New York/NY, U.S.A.

by Dr. Sebastian Sobottka, Maite Nößler, Dr. Andrew L. Ostericher, Dr. Gunter Hermann, Noah Z. Subat, Julia Beerhues, Dr. Margarethe Behr‐van der Meer, Dr. Lisa Suntrup, Dr. Uta Albold, Dr. Stephan Hohloch, Dr. Jean Christophe Tremblay, Prof. Dr. Biprajit Sarkar

Chem. Eur. J. 2020, 26, 1314
DOI: 10.1002/chem.201903700

For further information please contact:
Prof. Biprajit Sarkar
Institute of Inorganic Chemistry
University of Stuttgart

by Merlin Kleoff, Johannes Schwan, Lisa Boeser, Bence Hartmayer, Mathias Christmann*, Biprajit Sarkar*, Philipp Heretsch*

Org. Lett. 2020, 22, 3, 902
DOI: 10.1021/acs.orglett.9b04450

For further information please contact:
Prof. Biprajit Sarkar
Institute of Inorganic Chemistry
University of Stuttgart

by Fei Jia, Hendrik V. Schröder, Liu-Pan Yang, Carolina von Essen, Sebastian Sobottka, Biprajit Sarkar, Kari Rissanen, Wei Jiang*, Christoph A. Schalley*

J. Am. Chem. Soc. 2020
DOI: 10.1021/jacs.9b11685

For further information please contact:
Prof. Biprajit Sarkar
Institute of Inorganic Chemistry
University of Stuttgart

by Hofacker D., Broche J., Laistner L., Adam S., Bashtrykov P.  and Jeltsch A.

Targeted DNA methylation is a promising approach for the modulation of gene expression in basic research and in the clinic. However, it often suffers from a lack of specificity, because off-target regions also are methylated. We have rationally designed different DNMT3A variants with reduced DNA binding and applied them for targeted methylation. Our data show that this leads to a pronounced improvement in the specificity of targeted DNA methylation as indicated by a strongly reduced off-target methylation accompanied by an only mild reduction of on-target activity. These improved DNMT3A variants will advance the future applications of this emerging technology.

Int J Mol Sci. 2020 Jan 13;21(2)
doi: 10.3390/ijms21020502.

For further information please contact:
Prof. Albert Jeltsch
Institute of Biochemisty and Technical Biochemistry
University of Stuttgart

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