排序方式: 共有12条查询结果,搜索用时 15 毫秒
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Niels J. Hauwert Tamara A. M. Mocking Daniel DaCostaPereira Ken Lion Yara Huppelschoten Henry F. Vischer Iwan J. P. DeEsch Maikel Wijtmans Rob Leurs 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(14):4579-4583
Spatiotemporal control over biochemical signaling processes involving G protein‐coupled receptors (GPCRs) is highly desired for dissecting their complex intracellular signaling. We developed sixteen photoswitchable ligands for the human histamine H3 receptor (hH3R). Upon illumination, key compound 65 decreases its affinity for the hH3R by 8.5‐fold and its potency in hH3R‐mediated Gi protein activation by over 20‐fold, with the trans and cis isomer both acting as full agonist. In real‐time two‐electrode voltage clamp experiments in Xenopus oocytes, 65 shows rapid light‐induced modulation of hH3R activity. Ligand 65 shows good binding selectivity amongst the histamine receptor subfamily and has good photolytic stability. In all, 65 (VUF15000) is the first photoswitchable GPCR agonist confirmed to be modulated through its affinity and potency upon photoswitching while maintaining its intrinsic activity, rendering it a new chemical biology tool for spatiotemporal control of GPCR activation. 相似文献
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Matthew T. Richers Stefan Passlick Hitesh Agarwal Graham C. R. Ellis‐Davies 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(35):12214-12218
We have developed a caged neurotransmitter using an extended π‐electron chromophore for efficient multiphoton uncaging on living neurons. Widely studied in a chemical context, such chromophores are inherently bioincompatible due to their highly lipophilic character. Attachment of two polycarboxylate dendrimers, a method we call “cloaking”, to a bisstyrylthiophene (or BIST) core effectively transformed the chromophore into a water‐soluble optical probe, whilst maintaining the high two‐photon absorption of over 500 GM. Importantly, the cloaked caged compound was biologically inert at the high concentrations required for multiphoton chemical physiology. Thus, in contrast to non‐cloaked BIST compounds, the BIST‐caged neurotransmitter can be safely delivered onto neurons in acutely isolated brain slices, thereby enabling high‐resolution two‐photon uncaging without any side effects. We expect that our cloaking method will enable the development of new classes of cell‐compatible photolabile probes using a wide variety of extended π‐electron caging chromophores. 相似文献
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