ArticleBioconjugate chemistry2011
GPCR ligand dendrimer (GLiDe) conjugates: adenosine receptor interactions of a series of multivalent xanthine antagonists.
Article in Bioconjugate chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
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- Chemical Probes for the Adenosine Receptors.Pharmaceuticals (Basel, Switzerland) · 2019Review
- An Affinity-Based Probe for the Human Adenosine AJournal of medicinal chemistry · 2018Article
- Application of Nanoparticles for Targeting G Protein-Coupled Receptors.International journal of molecular sciences · 2018Review
- Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.Current neuropharmacology · 2016Review
- Recent advances in click chemistry applied to dendrimer synthesis.Molecules (Basel, Switzerland) · 2015Review
- Programmable nanoscaffolds that control ligand display to a G-protein-coupled receptor in membranes to allow dissection of multivalent effects.Journal of the American Chemical Society · 2014Article
- Synthesis of BODIPY derivatives substituted with various bioconjugatable linker groups: a construction kit for fluorescent labeling of receptor ligands.Journal of fluorescence · 2014Article
- Modulation of G protein-coupled adenosine receptors by strategically functionalized agonists and antagonists immobilized on gold nanoparticles.Purinergic signalling · 2013Article
- Structure-based approaches to ligands for G-protein-coupled adenosine and P2Y receptors, from small molecules to nanoconjugates.Journal of medicinal chemistry · 2013Review
- Fluorescent ligands for adenosine receptors.Bioorganic & medicinal chemistry letters · 2013Review
- Click modification in the N6 region of A3 adenosine receptor-selective carbocyclic nucleosides for dendrimeric tethering that preserves pharmacophore recognition.Bioconjugate chemistry · 2012Article
- Structure-activity relationships of truncated C2- or C8-substituted adenosine derivatives as dual acting A₂A and A₃ adenosine receptor ligands.Journal of medicinal chemistry · 2012Article
- Polyamidoamine (PAMAM) dendrimer conjugate specifically activates the A3 adenosine receptor to improve post-ischemic/reperfusion function in isolated mouse hearts.BMC pharmacology · 2011Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Previously, G protein-coupled receptor (GPCR) agonists were tethered from polyamidoamine (PAMAM) dendrimers to provide high receptor affinity and selectivity. Here, we prepared GPCR ligand--dendrimer (GLiDe) conjugates from a potent adenosine receptor (AR) antagonist; such agents are of interest for treating Parkinson's disease, asthma, and other conditions. Xanthine amine congener (XAC) was appended with an alkyne group on an extended C8 substituent for coupling by Cu(I)-catalyzed click chemistry to azide-derivatized G4 (fourth-generation) PAMAM dendrimers to form triazoles. These conjugates also contained triazole-linked PEG groups (8 or 22 moieties per 64 terminal positions) for increasing water-solubility and optionally prosthetic groups for spectroscopic characterization and affinity labeling. Human AR binding affinity increased progressively with the degree of xanthine substitution to reach K(i) values in the nanomolar range. The order of affinity of each conjugate was hA(2A)AR > hA(3)AR > hA(1)AR, while the corresponding monomer was ranked hA(2A)AR > hA(1)AR ≥ hA(3)AR. The antagonist activity of the most potent conjugate 14 (34 xanthines per dendrimer) was examined at the G(i)-coupled A(1)AR. Conjugate 14 at 100 nM right-shifted the AR agonist concentration--response curve in a cyclic AMP functional assay in a parallel manner, but at 10 nM (lower than its K(i) value), it significantly suppressed the maximal agonist effect in calcium mobilization. This is the first systematic probing of a potent AR antagonist tethered on a dendrimer and its activity as a function of variable loading.
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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.