Development and Validation of a Fluorogenic Probe for Lysosomal Zinc Release

Author:

Shukla Adarash Kumar1ORCID,Mahale Ashutosh2,Choudhary Savita1ORCID,Sharma Pravesh2ORCID,Kulkarni Onkar Prakash2,Bhattacharya Anupam1ORCID

Affiliation:

1. Department of Chemistry Birla Institute of Technology and Science-Pilani (Hyderabad Campus) Hyderabad 500078 India

2. Department of Pharmacy Birla Institute of Technology and Science-Pilani (Hyderabad Campus) Hyderabad 500078 India

Abstract

AbstractZinc homeostasis, which allows optimal zinc utilization in diverse life processes, is responsible for the general well‐being of human beings. This paper describes developing and validating an easily accessible indole‐containing zinc‐specific probe in the cellular milieu. The probe was synthesized from readily available starting materials and was subjected to steady‐state fluorescence studies. It showed selective sensing behavior towards Zn2+ with reversible binding. The suppression of PET (Photoinduced Electron Transfer) and ESIPT (Excited State Intramolecular Proton Transfer) elicited selectivity, and the detection limit was 0.63 μM (LOQ 6.8 μM). The zinc sensing capability of the probe was also screened in the presence of low molecular weight ligands [LMWLs] and showed interference only with GSH and ATP. It is non‐toxic and can detect zinc in different cell lines under various stress conditions such as inflammation, hyperglycemia, and apoptosis. The probe could stain the early and late stages of apoptosis in PAN‐2 cells by monitoring the zinc release. Most experiments were conducted without external zinc supplementation, showing its innate ability to detect zinc.

Funder

Department of Chemistry, University of York

Publisher

Wiley

Subject

Organic Chemistry,Molecular Biology,Molecular Medicine,Biochemistry

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