showing 23 related works from this author
Approaching an experimental electron density model of the biologically active trans ‐epoxysuccinyl amide group—Substituent effects vs. crystal packing
2017
The trans-epoxysuccinyl amide group as a biologically active moiety in cysteine protease inhibitors such as loxistatin acid E64c has been used as a benchmark system for theoretical studies of environmental effects on the electron density of small active ingredients in relation to their biological activity. Here, the synthesis and the electronic properties of the smallest possible active site model compound are reported to close the gap between the unknown experimental electron density of trans-epoxysuccinyl amides and the well-known function of related drugs. Intramolecular substituent effects are separated from intermolecular crystal packing effects on the electron density, which allows us…
Synthesis, X-ray Structure Determination, and Comprehensive Photochemical Characterization of (Trifluoromethyl)diazirine-Containing TRPML1 Ligands
2021
Potential (trifluoromethyl)diazirine-based TRPML1 ion channel ligands were designed and synthesized, and their structures were determined by single-crystal X-ray diffraction analysis. Photoactivation studies via 19F NMR spectroscopy and HPLC-MS analysis revealed distinct kinetical characteristics in selected solvents and favorable photochemical properties in an aqueous buffer. These photoactivatable TRPML activators represent useful and valuable tools for TRPML photoaffinity labeling combined with mass spectrometry.
Can Experimental Electron-Density Studies be Used as a Tool to Predict Biologically Relevant Properties of Low-Molecular Weight Enzyme Ligands?
2013
The case of protease inhibitor model compounds incorporating an aziridine or epoxide ring is used to exemplify how application of experimental electron-density techniques can be used to explain the biological properties of low-molecular weight enzyme ligands. This is furthermore seen in the light of a comparison of crystal and enzyme environments employing QM/MM computations to elucidate to which extent the properties in the crystal can be used to predict behavior in the biological surrounding.
Electrostatic complementarity in pseudoreceptor modeling based on drug molecule crystal structures: the case of loxistatin acid (E64c)
2015
After a long history of use as a prototype cysteine protease inhibitor, the crystal structure of loxistatin acid (E64c) is finally determined experimentally using intense synchrotron radiation, providing insight into how the inherent electronic nature of this protease inhibitor molecule determines its biochemical activity. Based on the striking similarity of its intermolecular interactions with those observed in a biological environment, the electrostatic potential of crystalline E64c is used to map the characteristics of a pseudo-enzyme pocket.
Vinyl sulfone building blocks in covalently reversible reactions with thiols
2015
In the present study we use quantum-chemical calculations to investigate how the reactivity of vinyl sulfone-based compounds can be modified from an irreversible to a reversible reaction with thiols. Based on the predictions from theory, an array of nine different vinyl sulfones with systematically varying substitution pattern was synthesized and their crystal structures were determined. Subsequent Hirshfeld surface analyses employing the principle of electrostatic complementarity aid the understanding of the crystal packing of the synthesized compounds. Reactivity studies against the nucleophile 2-phenylethanethiol mirror the properties predicted by the quantum-chemical computations in sol…
The Significance of Ionic Bonding in Sulfur Dioxide: Bond Orders from X-ray Diffraction Data
2012
A novel refinement technique for X‐ray diffraction data has been employed to derive S-O bond orders in sulfur dioxide experimentally. The results show that ionic S-O bonding dominates over hypervalency.
Similarities and differences between crystal and enzyme environmental effects on the electron density of drug molecules
2021
Abstract The crystal interaction density is generally assumed to be a suitable measure of the polarization of a low‐molecular weight ligand inside an enzyme, but this approximation has seldomly been tested and has never been quantified before. In this study, we compare the crystal interaction density and the interaction electrostatic potential for a model compound of loxistatin acid (E64c) with those inside cathepsin B, in solution, and in vacuum. We apply QM/MM calculations and experimental quantum crystallography to show that the crystal interaction density is indeed very similar to the enzyme interaction density. Less than 0.1 e are shifted between these two environments in total. Howeve…
Die Bedeutung ionischer Bindungsanteile in Schwefeldioxid - Bindungsordnungen aus Röntgenbeugungsdaten
2012
CCDC 1498221: Experimental Crystal Structure Determination
2017
Related Article: Ming W. Shi, Scott G. Stewart, Alexandre N. Sobolev, Birger Dittrich, Tanja Schirmeister, Peter Luger, Malte Hesse, Yu-Sheng Chen, Peter R. Spackman,Mark A. Spackman, Simon Grabowsky|2017|J.Phys.Org.Chem.|30|e3683|doi:10.1002/poc.3683
CCDC 897063: Experimental Crystal Structure Determination
2015
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 897056: Experimental Crystal Structure Determination
2015
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 897057: Experimental Crystal Structure Determination
2015
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 2046165: Experimental Crystal Structure Determination
2021
Related Article: Kevin Schwickert, Micha Andrzejewski, Simon Grabowsky, Tanja Schirmeister|2021|J.Org.Chem.|86|6169|doi:10.1021/acs.joc.0c02993
CCDC 977799: Experimental Crystal Structure Determination
2015
Related Article: Ming W. Shi, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Thomas C. Schmidt, Peter Luger, Stefan Mebs, Birger Dittrich, Yu-Sheng Chen, Joanna M. Bąk, Dylan Jayatilaka, Charles S. Bond, Michael J. Turner, Scott G. Stewart, Mark A. Spackman and Simon Grabowsky|2015|New J.Chem.|39|1628|doi:10.1039/C4NJ01503G
CCDC 897062: Experimental Crystal Structure Determination
2015
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 897061: Experimental Crystal Structure Determination
2015
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 2046164: Experimental Crystal Structure Determination
2021
Related Article: Kevin Schwickert, Micha Andrzejewski, Simon Grabowsky, Tanja Schirmeister|2021|J.Org.Chem.|86|6169|doi:10.1021/acs.joc.0c02993
CCDC 897060: Experimental Crystal Structure Determination
2015
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 897059: Experimental Crystal Structure Determination
2015
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 2024395: Experimental Crystal Structure Determination
2021
Related Article: Florian Kleemiss, Erna K. Wieduwilt, Emanuel Hupf, Ming W. Shi, Scott G. Stewart, Dylan Jayatilaka, Michael J. Turner, Kunihisa Sugimoto, Eiji Nishibori, Tanja Schirmeister, Thomas C. Schmidt, Bernd Engels, Simon Grabowsky|2021|Chem.-Eur.J.|27|3407|doi:10.1002/chem.202003978
CCDC 897058: Experimental Crystal Structure Determination
2015
Related Article: Thomas H. Schneider, Max Rieger, Kay Ansorg, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Simon Grabowsky|2015|New J.Chem.|39|5841|doi:10.1039/C5NJ00368G
CCDC 1498219: Experimental Crystal Structure Determination
2017
Related Article: Ming W. Shi, Scott G. Stewart, Alexandre N. Sobolev, Birger Dittrich, Tanja Schirmeister, Peter Luger, Malte Hesse, Yu-Sheng Chen, Peter R. Spackman,Mark A. Spackman, Simon Grabowsky|2017|J.Phys.Org.Chem.|30|e3683|doi:10.1002/poc.3683
CCDC 1498220: Experimental Crystal Structure Determination
2017
Related Article: Ming W. Shi, Scott G. Stewart, Alexandre N. Sobolev, Birger Dittrich, Tanja Schirmeister, Peter Luger, Malte Hesse, Yu-Sheng Chen, Peter R. Spackman,Mark A. Spackman, Simon Grabowsky|2017|J.Phys.Org.Chem.|30|e3683|doi:10.1002/poc.3683