Red‐ and Far‐Red‐Emitting Zinc Probes with Minimal Phototoxicity for Multiplexed Recording of Orchestrated Insulin Secretion. (15th September 2021)

• Record Type: Journal Article
• Authors: Zhang, Junwei; Peng, Xiaohong; Wu, Yunxiang; Ren, Huixia; Sun, Jingfu; Tong, Shiyan; Liu, Tianyan; Zhao, Yiwen; Wang, Shusen; Tang, Chao; Chen, Liangyi; Chen, Zhixing
• Is Part Of: Angewandte Chemie. Volume 133:Number 49(2021)
• Page Start: 26050
• Page End: 26059
• Publication Date: 2021-09-15
• Subjects: 4D islet physiology -- biocompatibility -- fluorescent probe -- insulin secretion -- zinc; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202109510
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Zinc biology, featuring intertwining signaling networks and critical importance to human health, witnesses exciting opportunities in the big data era of physiology. Here, we report a class of red‐ and far‐red‐emitting Zn 2+ probes with K d values ranging from 190 nM to 74 μM, which are particularly suitable for real‐time monitoring the high concentration of Zn 2+ co‐released with insulin during vesicular secretory events. Compared to the prototypical rhodamine‐based Zn 2+ probes, the new class exploits morpholino auxochromes which eliminates phototoxicity during long‐term live recording of isolated islets. A Si‐rhodamine‐based Zn 2+ probe with high turn‐on ratio (>100), whose synthesis was enabled by a new route featuring late‐stage N‐alkylation, allowed simultaneous recording of Ca 2+ influx, mitochondrial signal, and insulin secretion in isolated mouse islets. The time‐lapse multicolor fluorescence movies and their analysis, enabled by red‐shifted Zn 2+ and other orthogonal physiological probes, highlight the potential impact of biocompatible fluorophores on the fields of islet endocrinology and system biology. Abstract : We synthesized a new class of red‐ and far‐red‐emitting Zn 2+ probes with minimal phototoxicity, μM affinities and high turn‐on ratios. Tailored for 4D, long‐term and multiple‐color recording of Zn 2+ /insulin co‐secretion in β‐cells and islets, the new probes promise to unveil the spatial‐temporal regulation of islet endocrinology.