Endoplasmic reticulum targeting fluorescent probes to image mobile Zn²

Area of Science:

• Biochemistry
• Cell Biology
• Chemical Biology

Background:

• Zinc ions (Zn²⁺) are crucial for endoplasmic reticulum (ER) function.
• Zn²⁺ deficiency can lead to ER stress, implicated in various diseases.
• Understanding mobile Zn²⁺ dynamics in the ER is vital for disease research.

Purpose of the Study:

• To develop novel, ER-localized fluorescent probes for imaging mobile Zn²⁺.
• To create tools for investigating the role of Zn²⁺ in ER homeostasis and stress.
• To facilitate research into ER-related diseases linked to zinc dysregulation.

Main Methods:

• Design and synthesis of custom ER-localized fluorescent Zn²⁺ probes.
• Incorporation of a cyclohexyl sulfonylurea ER-targeting unit.
• In vitro and in cellulo experiments to evaluate probe performance.

Main Results:

• Developed two novel ER-localized fluorescent Zn²⁺ probes.
• Probes exhibited excellent Zn²⁺ response, high selectivity, low toxicity, and ER-specific targeting.
• Demonstrated efficacy in imaging mobile Zn²⁺ across four cell lines.
• Probe 9 successfully detected Zn²⁺ changes during ER stress.

Conclusions:

• The new fluorescent probes are effective tools for visualizing mobile Zn²⁺ in the ER.
• These probes will advance the understanding of cellular responses to ER zinc dyshomeostasis.
• This research aids in elucidating the role of ER zinc in disease initiation and progression.