ArticleJournal of nanobiotechnology2008
Enhanced A3 adenosine receptor selectivity of multivalent nucleoside-dendrimer conjugates.
Article in Journal of nanobiotechnology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Probing structure-activity relationship in β-arrestin2 recruitment of diversely substituted adenosine derivatives.Biochemical pharmacology · 2018Article
- Characterization of Polyamidoamino (PAMAM) Dendrimers Using In-Line Reversed Phase LC Electrospray Ionization Mass Spectrometry.Analytical methods : advancing methods and applications · 2016Article
- Fluorescent ligands for adenosine receptors.Bioorganic & medicinal chemistry letters · 2013Review
- Structural sweet spot for A1 adenosine receptor activation by truncated (N)-methanocarba nucleosides: receptor docking and potent anticonvulsant activity.Journal of medicinal chemistry · 2012Article
- GPCR ligand dendrimer (GLiDe) conjugates: adenosine receptor interactions of a series of multivalent xanthine antagonists.Bioconjugate chemistry · 2011Article
- Recent developments in adenosine receptor ligands and their potential as novel drugs.Biochimica et biophysica acta · 2011Review
- GPCR ligand-dendrimer (GLiDe) conjugates: future smart drugs?Trends in pharmacological sciences · 2010Article
- Novel Alexa Fluor-488 labeled antagonist of the A(2A) adenosine receptor: Application to a fluorescence polarization-based receptor binding assay.Biochemical pharmacology · 2010Article
- Functionalized congeners of P2Y1 receptor antagonists: 2-alkynyl (N)-methanocarba 2'-deoxyadenosine 3',5'-bisphosphate analogues and conjugation to a polyamidoamine (PAMAM) dendrimer carrier.Bioconjugate chemistry · 2010Article
- Multivalent dendrimeric and monomeric adenosine agonists attenuate cell death in HL-1 mouse cardiomyocytes expressing the A(3) receptor.Biochemical pharmacology · 2010Article
- Nucleoside conjugates of quantum dots for characterization of G protein-coupled receptors: strategies for immobilizing A2A adenosine receptor agonists.Journal of nanobiotechnology · 2010Article
- Polyamidoamine (PAMAM) dendrimer conjugates of "clickable" agonists of the A3 adenosine receptor and coactivation of the P2Y14 receptor by a tethered nucleotide.Bioconjugate chemistry · 2010Article
- Functionalized congener approach to the design of ligands for G protein-coupled receptors (GPCRs).Bioconjugate chemistry · 2009Review
- Enhanced potency of nucleotide-dendrimer conjugates as agonists of the P2Y14 receptor: multivalent effect in G protein-coupled receptor recognition.Bioconjugate chemistry · 2009Article
- Introduction to adenosine receptors as therapeutic targets.Handbook of experimental pharmacology · 2009Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAn approach to use multivalent dendrimer carriers for delivery of nucleoside signaling molecules to their cell surface G protein-coupled receptors (GPCRs) was recently introduced.
resultsA known adenosine receptor (AR) agonist was conjugated to polyamidoamine (PAMAM) dendrimer carriers for delivery of the intact covalent conjugate to on the cell surface. Depending on the linking moiety, multivalent conjugates of the N6-chain elongated functionalized congener ADAC (N6-[4-[[[4-[[[(2-aminoethyl)amino]carbonyl]methyl]anilino]carbonyl]methyl]phenyl]-adenosine) achieved unanticipated high selectivity in binding to the cytoprotective human A3 AR, a class A GPCR. The key to this selectivity of > 100-fold in both radioreceptor binding (Ki app = 2.4 nM) and functional assays (EC50 = 1.6 nM in inhibition of adenylate cyclase) was maintaining a free amino group (secondary) in an amide-linked chain. Attachment of neutral amide-linked chains or thiourea-containing chains preserved the moderate affinity and efficacy at the A1 AR subtype, but there was no selectivity for the A3 AR. Since residual amino groups on dendrimers are associated with cytotoxicity, the unreacted terminal positions of this A3 AR-selective G2.5 dendrimer were present as carboxylate groups, which had the further benefit of increasing water-solubility. The A3 AR selective G2.5 dendrimer was also visualized binding the membrane of cells expressing the A3 receptor but did not bind cells that did not express the receptor.
conclusionThis is the first example showing that it is feasible to modulate and even enhance the pharmacological profile of a ligand of a GPCR based on conjugation to a nanocarrier and the precise structure of the linking group, which was designed to interact with distal extracellular regions of the 7 transmembrane-spanning receptor. This ligand tool can now be used in pharmacological models of tissue rescue from ischemia and to probe the existence of A3 AR dimers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.