TY - JOUR
T1 - Acid‐Resistant BODIPY Amino Acids for Peptide‐based Fluorescence Imaging of GPR54 Receptors in Pancreatic Islets
AU - Mendive-Tapia, Lorena
AU - Miret-Casals, Laia
AU - Barth, Nicole
AU - Wang, Jinling
AU - De bray, Anne
AU - Beltramo, Massimiliano
AU - Robert, Vincent
AU - Ampe, Christophe
AU - Hodson, David
AU - Madder, Annemieke
AU - Vendrell, Marc
N1 - Funding Information:
L.M.T acknowledges funding from the Wellcome Trust‐University of Edinburgh Institutional Strategic Support Fund (204804/Z/16/Z). L.M.C. acknowledges UGent for a position as postdoctoral assistant and funding from FWO/Embassy of France in Belgium‐Campus France (joint exchange/mobility project Tournesol: VS01022N). N.D.B. acknowledges funds from the Wellcome Trust (221647/Z/20/Z). A.B. was supported by an MRC Clinical Research Training Fellowship (MR/W000881/1). C.A. and A.M. acknowledge funding from the UGent Special Research Fund (BOF) through the MemCLiP concerted research action. D.J.H. was supported by an MRC Project Grant (MR/S025618/1), a UKRI Frontier Research Guarantee Grant (EP/X026833/1), an ERC Starting Grant (715884) and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. M.V. acknowledges funds from an ERC Consolidator Grant (DYNAFLUORS, 771443). The authors also acknowledge Dr. Johannes Broichhagen (FMP Leibniz, Berlin) for the provision of LUXendin645. D.J.H. receives licensing revenue from Celtarys Research for provision of chemical probes. For open access, the authors have applied a CC‐BY public copyright license to any Author Accepted Manuscript version arising from this submission. The authors acknowledge BioRender.com for assistance with Figure creation. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
Publisher Copyright:
© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
PY - 2023/3/14
Y1 - 2023/3/14
N2 - 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.
AB - 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.
U2 - 10.1002/anie.202302688
DO - 10.1002/anie.202302688
M3 - Article
SN - 1433-7851
JO - Angewandte Chemie International Edition
JF - Angewandte Chemie International Edition
ER -