The G protein-coupled kisspeptin receptor (GPR54 or KISS1R) is an important mediator in reproduction, metabolism and cancer biology; however, there are limited fluorescent probes or antibodies for direct imaging of these receptors in cells and intact tissues, which can help to interrogate their multiple biological roles. Herein, we describe the rational design and characterization of a new acid-resistant BODIPY-based amino acid (Trp-BODIPY PLUS), and its implementation for solid-phase synthesis of fluorescent bioactive peptides. Trp-BODIPY PLUS retains the binding capabilities of both short linear and cyclic peptides and displays notable turn-on fluorescence emission upon target binding for wash-free imaging. Finally, we employed Trp-BODIPY PLUS to prepare some of the first fluorogenic kisspeptin-based probes and visualized the expression and localization of GPR54 receptors in human cells and in whole mouse pancreatic islets by fluorescence imaging.
We describe Trp‐BODIPY PLUS as a new acid‐resistant building block for straightforward solid‐phase synthesis of fluorogenic peptides. We demonstrate the utility of Trp‐BODIPY PLUS with the first fluorogenic probe for direct visualization and quantitative analysis of the expression and localization of the G protein‐coupled receptors 54 (GPR54 or kisspeptin) in human cells and intact mouse pancreatic islets.
Keywords: Diabetes; Fluorescence; GPCRs; Probes; Solid-Phase Peptide Synthesis.
© 2023 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.