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• W2108345530 abstract "Sigma (σ) receptors are unique non-opioid binding sites that are associated with a broad range of disease states. Sigma-2 receptors provide a promising target for diagnostic imaging and pharmacological interventions to curb tumor progression. Most recently, the progesterone receptor (PGRMC1, 25 kDa) has been shown to have σ2 receptor-like binding properties, thus highlighting the need to understand the biological function of an 18 kDa protein that exhibits σ2-like photoaffinity labeling (denoted here as σ2-18k) but the amino acid sequence of which is not known. In order to provide new tools for the study of the σ2-18k protein, we have developed bifunctional σ receptor ligands each bearing a benzophenone photo-crosslinking moiety and an alkyne group to which an azide-containing biotin affinity tag can be covalently attached through click chemistry after photo-crosslinking. Although several compounds showed favorable σ2 binding properties, the highest affinity (2 nM) and the greatest potency in blocking photolabeling of σ2-18k by a radioactive photoaffinity ligand was shown by compound 22. These benzophenone-alkyne σ receptor ligands might therefore be amenable for studying the σ2-18k protein through chemical biology approaches. To the best of our knowledge, these compounds represent the first reported benzophenone-containing clickable σ receptor ligands, which might potentially have broad applications based on the plugging in of various tags." @default.
• W2108345530 created "2016-06-24" @default.
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• W2108345530 date "2012-09-23" @default.
• W2108345530 modified "2023-10-10" @default.
• W2108345530 title "Development of Benzophenone-Alkyne Bifunctional Sigma Receptor Ligands" @default.
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• W2108345530 doi "https://doi.org/10.1002/cbic.201200427" @default.
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