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Characterization of fluorescent GPCR‐ligand dendrimer (GLiDe) conjugates in binding to the A3 adenosine receptors

We are developing novel GPCR‐ligand dendrimer (GLiDe) conjugates that target purine receptors. Dendrimers are highly branched, monodisperse, synthetic macromolecules with defined composition and molecular architecture. Recent advances in dendrimer‐based nanomedicine show that dendrimers, especially biocompatible poly(amidoamine) (PAMAM) dendrimers, can be covalently modified with targeting ligands, fluorescent dyes, and drugs for targeted imaging and therapeutics. In the present study, PAMAM dendrimers containing peripheral azido groups were coupled to agonists of the A3 adenosine receptor and fluorescent dyes through click chemistry. These GLiDe conjugates demonstrated high receptor affinity and potency. These conjugates bound to A3 receptors were visualized by fluorescent microscopy. Also, the relative fluorescent intensity was measured using flow cytometry. These A3 adenosine receptor multivalent agonists with fluorescent ligands promise to be useful tools for selective targeting, drug delivery, and imaging for various biomedical applications. This work was supported by the Intramural Research Program of NIDDK, NIH, Bethesda, MD, USA.