0000000000727124

AUTHOR

Kevin Schwickert

Synthesis, X-ray Structure Determination, and Comprehensive Photochemical Characterization of (Trifluoromethyl)diazirine-Containing TRPML1 Ligands

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.

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Structure of the Human TRPML2 Ion Channel Extracytosolic/Lumenal Domain.

Summary TRPML2 is the least structurally characterized mammalian transient receptor potential mucolipin ion channel. The TRPML family hallmark is a large extracytosolic/lumenal domain (ELD) between transmembrane helices S1 and S2. We present crystal structures of the tetrameric human TRPML2 ELD at pH 6.5 (2.0 A) and 4.5 (2.95 A), corresponding to the pH values in recycling endosomes and lysosomes. Isothermal titration calorimetry shows Ca2+ binding to the highly acidic central pre-pore loop which is abrogated at low pH, in line with a pH-dependent channel regulation model. Small angle X-ray scattering confirms the ELD dimensions in solution. Changes in pH or Ca2+ concentration do not affect…

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Ruthenium(II) and platinum(II) homo- and heterobimetallic complexes: Synthesis, crystal structures, theoretical calculations and biological studies

Four Ru-Pd heterobimetallic complexes, each one in two different coordination modes (NNSS and NS) having metals connected by a binucleating dialkyldithiooxamidate [N(R)SC-CS(R)N] [R = methyl, ethyl, n-butyl and isopropyl], were prepared by reacting the monochelate [(trinpropyl-phosphine)ClPd(HR2C2N2S2κ-S,S-Pd)] with [(η6-p-cymene)RuCl2]2. Furthermore, two palladium homobimetallic complexes having two (trinpropyl-phosphine)ClPd moieties joined by a diethyldithiooxamidate in both κ-N,S Pd, κ-N',S' Pd' and κ-N,N' Pd, κ-S,S' Pd' coordination modes were synthesized. For both kinds of complexes, homo- and heterobimetallic, at room temperature and in chloroform solution, the NNSS coordination mode…

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CCDC 2046165: Experimental Crystal Structure Determination

Related Article: Kevin Schwickert, Micha Andrzejewski, Simon Grabowsky, Tanja Schirmeister|2021|J.Org.Chem.|86|6169|doi:10.1021/acs.joc.0c02993

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CCDC 1920565: Experimental Crystal Structure Determination

Related Article: Banafshe Askari, Hadi Amiri Rudbari, Nicola Micale, Tanja Schirmeister, Thomas Efferth, Ean-Jeong Seo, Giuseppe Bruno, Kevin Schwickert|2019|Dalton Trans.|48|15869|doi:10.1039/C9DT02353D

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CCDC 2046164: Experimental Crystal Structure Determination

Related Article: Kevin Schwickert, Micha Andrzejewski, Simon Grabowsky, Tanja Schirmeister|2021|J.Org.Chem.|86|6169|doi:10.1021/acs.joc.0c02993

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CCDC 1920566: Experimental Crystal Structure Determination

Related Article: Banafshe Askari, Hadi Amiri Rudbari, Nicola Micale, Tanja Schirmeister, Thomas Efferth, Ean-Jeong Seo, Giuseppe Bruno, Kevin Schwickert|2019|Dalton Trans.|48|15869|doi:10.1039/C9DT02353D

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