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Abstract：
Despite their controversial physiology, sigma-1 (σ1) receptors are intriguing targets for the development of therapeutic agents for central nervous system diseases. With the aim of providing versatile pharmacological tools to study σ1 receptors, we developed three σ1 fluorescent tracers by functionalizing three well characterized σ1 ligands with a fluorescent tag. A good compromise between σ1 binding affinity and fluorescent properties was reached, and the σ1 specific targeting of the novel tracers was demonstrated by confocal microscopy and flow cytometry. These novel ligands were also successfully used in competition binding studies by flow cytometry, showing their utility in nonradioactive binding assays as an alternative strategy to the more classical radioligand binding assays. To the best of our knowledge these are the first σ1 fluorescent ligands to be developed and successfully employed in living cells, representing promising tools to strengthen σ1 receptors related studies.
摘要：
尽管他们的生理学有争议，sigma-1（σ1）受体是开发中枢神经系统疾病治疗剂的有趣靶标。为了提供通用的药理学工具来研究σ1受体，我们通过用荧光标签官能化三个特征良好的σ1配体开发了三个σ1荧光示踪剂。在σ1结合亲和力和荧光性质之间达成了良好的折衷，通过共聚焦显微镜和流式细胞术证明了新型示踪剂的σ1特异性靶向。这些新型配体也通过流式细胞术成功用于竞争结合研究，显示它们在非放射性结合测定中的实用性，作为更经典的放射性配体结合测定的替代策略。据我们所知，这些是第一个被开发并成功用于活细胞的σ1荧光配体，代表有希望的工具，以加强σ1受体相关的研究。
