Design, synthesis and characterization of a fluorescently labeled functional analog of full-length human ghrelin

Mengjie Liu; Emily A Whitfield; Linda J Fothergill; John B Furness; John D Wade; Sebastian G B Furness; Mohammed Akhter Hossain

doi:10.1016/j.bbrc.2020.09.028

Design, synthesis and characterization of a fluorescently labeled functional analog of full-length human ghrelin

Biochem Biophys Res Commun. 2020 Dec 10;533(3):559-564. doi: 10.1016/j.bbrc.2020.09.028. Epub 2020 Sep 23.

Authors

Mengjie Liu¹, Emily A Whitfield², Linda J Fothergill³, John B Furness⁴, John D Wade⁵, Sebastian G B Furness⁶, Mohammed Akhter Hossain⁷

Affiliations

¹ Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3010, Australia.
² Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
³ Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, 3010, Australia.
⁴ Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3010, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, 3010, Australia.
⁵ Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3010, Australia; School of Chemistry, The University of Melbourne, Parkville, VIC, 3010, Australia.
⁶ Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia. Electronic address: sebastian.furness@monash.edu.
⁷ Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3010, Australia; School of Chemistry, The University of Melbourne, Parkville, VIC, 3010, Australia. Electronic address: akhter.hossain@unimelb.edu.au.

PMID: 32980116
DOI: 10.1016/j.bbrc.2020.09.028

Abstract

Human ghrelin receptor (GHSR) is a recognized prospective target in the diagnosis and therapy of multiple cancer types. To gain a better understanding of this receptor signaling system, we have synthesized a novel full-length ghrelin analog that is fluorescently labeled at the side-chain of a C-terminal cysteine extension. This analog exhibited nanomolar affinity and potency for the ghrelin receptor. It shows comparable efficacy with that of endogenous ghrelin. The fluorescently-labeled ghrelin analog is a valuable tool for in vitro imaging of cell lines that express ghrelin receptor.

Keywords: Fluorescent proteins; G protein-coupled receptor; GHSR; GHSR-1a; GPCR; Ghrelin; Ghrelin receptor; Imaging; Labeling; ligand binding.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Fluorescence
Ghrelin / analogs & derivatives*
Ghrelin / chemical synthesis*
HEK293 Cells
Humans
Luminescent Proteins / chemical synthesis*
Luminescent Proteins / chemistry
Luminescent Proteins / metabolism*
Receptors, Ghrelin / metabolism

Substances

Ghrelin
Luminescent Proteins
Receptors, Ghrelin