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Updated: Feb 15, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
Design, Synthesis, and Evaluation of N- and C-Terminal Protein Bioconjugates as G Protein-Coupled Receptor Agonists
Robert D Healey1, Jonathan P Wojciechowski1, Ana Monserrat-Martinez1
1School of Chemistry, the Australian Centre for Nanomedicine and the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, §School of Medical Sciences, ‡EMBL Australia Node of Single Molecule Science, and ⊥School of Biotechnology and Biomolecular Sciences, University of New South Wales , Sydney, 2052 New South Wales, Australia.
Abstract:
A G protein-coupled receptor (GPCR) agonist protein, thaumatin, was site-specifically conjugated at the N- or C-terminus with a fluorophore for visualization of GPCR:agonist interactions. The N-terminus was specifically conjugated using a synthetic 2-pyridinecarboxyaldehyde reagent. The interaction profiles observed for N- and C-terminal conjugates were varied; N-terminal conjugates interacted very weakly with the GPCR of interest, whereas C-terminal conjugates bound to the receptor. These chemical biology tools allow interactions of therapeutic proteins:GPCR to be monitored and visualized. The methodology used for site-specific bioconjugation represents an advance in application of 2-pyridinecarboxyaldehydes for N-terminal specific bioconjugations.
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