biostudies-literaturePrasad PKIsrael Science FoundationMinerva Foundatione2411730https://www.ebi.ac.uk/biostudies/studies/S-EPMC12372432biostudies-literatureUnknown21(33)Turn-on fluorescent probes consisting of dye-ligand conjugates serve as a powerful tool for detecting cell surface proteins (CSPs) and their interactions with binding partners. However, generating such probes from protein-based ligands remains challenging. This challenge became particularly evident during the COVID-19 pandemic, which highlighted the need for assays to evaluate inhibitors of the interaction between the SARS-CoV-2 virus receptor-binding domain (RBD) and the angiotensin-converting enzyme 2 (ACE2) receptor. To sense this interaction in a cellular environment using turn-on probes, a tri-nitrilotriacetic acid (tri-NTA) unit was conjugated to quinoline-based cyanine (QBC) dyes. This design leverages the high affinity of tri-NTA for His-tag, along with the low-background and confiSmall (Weinheim an der Bergstrasse, Germany)Low-Background His-Tag-Targeting Probes for Turn-On Fluorescence Detection of Cell Surface Proteins and Their Binding Interactions.PMC12372432714437304/22Oppenheimer-Low NPrasad PKVishweshwara SSAvinoam OAnand SShanthamurthy CDKikkeri RUnger TAlbeck SToraskar SSirkis YFMotiei LMargulies DPetrovich-Kopitman EGranot TAddadi YRaigawali RYardeni EHKhan SfalseLow-Background His-Tag-Targeting Probes for Turn-On Fluorescence Detection of Cell Surface Proteins and Their Binding Interactions.Turn-on fluorescent probes consisting of dye-ligand conjugates serve as a powerful tool for detecting cell surface proteins (CSPs) and their interactions with binding partners. However, generating such probes from protein-based ligands remains challenging. This challenge became particularly evident during the COVID-19 pandemic, which highlighted the need for assays to evaluate inhibitors of the interaction between the SARS-CoV-2 virus receptor-binding domain (RBD) and the angiotensin-converting enzyme 2 (ACE2) receptor. To sense this interaction in a cellular environment using turn-on probes, a tri-nitrilotriacetic acid (tri-NTA) unit was conjugated to quinoline-based cyanine (QBC) dyes. This design leverages the high affinity of tri-NTA for His-tag, along with the low-background and confi2025-01-01T00:00:00Z2025 Aug2026-05-08T06:49:16.218Z2026-04-07T23:31:14.07ZS-EPMC123724324061323610.1002/smll.202411730