Publication Date

8-14-2024

Journal

Journal of the American Chemical Society

DOI

10.1021/jacs.4c05366

PMID

39079063

PMCID

PMC11722959

PubMedCentral® Posted Date

1-10-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Hydrogen Peroxide, Humans, Receptors, Androgen, Oxidation-Reduction

Abstract

Although many redox signaling molecules are present at low concentrations, typically ranging from micromolar to sub-micromolar levels, they often play essential roles in a wide range of biological pathways and disease mechanisms. However, accurately measuring low abundant analytes has been a significant challenge due to the lack of sensitivity and quantitative capability of existing measurement methods. In this study, we introduced a novel chemically induced amplifiable system for quantifying low-abundance redox signaling molecules in living cells. We utilized H2O2 as a proof-of-concept analyte and developed a probe that quantifies cellular peroxide levels by combining the NanoBiT system with androgen receptor (AR) dimerization as a reporting mechanism. Our system demonstrated a highly sensitive response to cellular peroxide changes induced both endogenously and exogenously. Furthermore, the system can be adapted for the quantification of other signaling molecules if provided with suitable probing chemistry.

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Graphical Abstract

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