0000000001309448
AUTHOR
Erika Diehl
showing 10 related works from this author
Inhibitor-Induced Dimerization of an Essential Oxidoreductase from African Trypanosomes
2018
Trypanosomal and leishmanial infections claim tens of thousands of lives each year. The metabolism of these unicellular eukaryotic parasites differs from the human host and their enzymes thus constitute promising drug targets. Tryparedoxin (Tpx) from Trypanosoma brucei is the essential oxidoreductase in the parasite's hydroperoxide-clearance cascade. In vitro and in vivo functional assays show that a small, selective inhibitor efficiently inhibits Tpx. With X-ray crystallography, SAXS, analytical SEC, SEC-MALS, MD simulations, ITC, and NMR spectroscopy, we show how covalent binding of this monofunctional inhibitor leads to Tpx dimerization. Intra- and intermolecular inhibitor-inhibitor, pro…
Metal‐Free Twofold Electrochemical C−H Amination of Activated Arenes: Application to Medicinally Relevant Precursor Synthesis
2020
Abstract The efficient production of many medicinally or synthetically important starting materials suffers from wasteful or toxic precursors for the synthesis. In particular, the aromatic non‐protected primary amine function represents a versatile synthetic precursor, but its synthesis typically requires toxic oxidizing agents and transition metal catalysts. The twofold electrochemical amination of activated benzene derivatives via Zincke intermediates provides an alternative sustainable strategy for the formation of new C−N bonds of high synthetic value. As a proof of concept, we use our approach to generate a benzoxazinone scaffold that gained attention as a starting structure against ca…
Structural Basis of TRPV4 N Terminus Interaction with Syndapin/PACSIN1-3 and PIP2
2018
Summary Transient receptor potential (TRP) channels are polymodally regulated ion channels. TRPV4 (vanilloid 4) is sensitized by PIP2 and desensitized by Syndapin3/PACSIN3, which bind to the structurally uncharacterized TRPV4 N terminus. We determined the nuclear magnetic resonance structure of the Syndapin3/PACSIN3 SH3 domain in complex with the TRPV4 N-terminal proline-rich region (PRR), which binds as a class I polyproline II (PPII) helix. This PPII conformation is broken by a conserved proline in a cis conformation. Beyond the PPII, we find that the proximal TRPV4 N terminus is unstructured, a feature conserved across species thus explaining the difficulties in resolving it in previous …
Inhibitor-induzierte Dimerisierung einer essentiellen Oxidoreduktase aus afrikanischen Trypanosomen
2019
Fluorovinylsulfones and -Sulfonates as Potent Covalent Reversible Inhibitors of the Trypanosomal Cysteine Protease Rhodesain: Structure–Activity Rela…
2021
Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, a pathogen causing Human African Trypanosomiasis, and a validated drug target. Recently, we reported the development of α-halovinylsulfones as a new class of covalent reversible cysteine protease inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, the most potent and selective inhibitor in the series, shows a single-digit nanomolar affinity and high selectivity toward mammalian cathepsins B and L. Enzymatic dilution assays and MS experiments indicate that 2d is a slow-tight binder (Ki = 3 nM). Furthermore, the nonfluorinated 2d-(H) shows favorabl…
CCDC 1998477: Experimental Crystal Structure Determination
2021
Related Article: Lars J. Wesenberg, Erika Diehl, Till J. B. Zähringer, Carolin Dörr, Dieter Schollmeyer, Akihiro Shimizu, Jun‐ichi Yoshida, Ute A. Hellmich, Siegfried R. Waldvogel|2020|Chem.-Eur.J.|26|17574|doi:10.1002/chem.202003852
CCDC 1998478: Experimental Crystal Structure Determination
2021
Related Article: Lars J. Wesenberg, Erika Diehl, Till J. B. Zähringer, Carolin Dörr, Dieter Schollmeyer, Akihiro Shimizu, Jun‐ichi Yoshida, Ute A. Hellmich, Siegfried R. Waldvogel|2020|Chem.-Eur.J.|26|17574|doi:10.1002/chem.202003852
CCDC 1998475: Experimental Crystal Structure Determination
2021
Related Article: Lars J. Wesenberg, Erika Diehl, Till J. B. Zähringer, Carolin Dörr, Dieter Schollmeyer, Akihiro Shimizu, Jun‐ichi Yoshida, Ute A. Hellmich, Siegfried R. Waldvogel|2020|Chem.-Eur.J.|26|17574|doi:10.1002/chem.202003852
CCDC 1862408: Experimental Crystal Structure Determination
2019
Related Article: Annika Wagner, Thien Anh Le, Martha Brennich, Philipp Klein, Nicole Bader, Erika Diehl, Daniel Paszek, A. Katharina Weickhmann, Natalie Dirdjaja, R. Luise Krauth-Siegel, Bernd Engels, Till Opatz, Hermann Schindelin, Ute A. Hellmich|2019|Angew.Chem.,Int.Ed.|58|3640|doi:10.1002/anie.201810470
CCDC 1998476: Experimental Crystal Structure Determination
2021
Related Article: Lars J. Wesenberg, Erika Diehl, Till J. B. Zähringer, Carolin Dörr, Dieter Schollmeyer, Akihiro Shimizu, Jun‐ichi Yoshida, Ute A. Hellmich, Siegfried R. Waldvogel|2020|Chem.-Eur.J.|26|17574|doi:10.1002/chem.202003852