title: Toward multivalent signaling across G protein-coupled receptors from poly(amidoamine) dendrimers.
abstract: Activation of the A2A receptor, a G protein-coupled receptor (GPCR), by extracellular adenosine, is antiaggregatory in platelets and anti-inflammatory. Multiple copies of an A2A agonist, the nucleoside CGS21680, were coupled covalently to PAMAM dendrimers and characterized spectroscopically. A fluorescent PAMAM-CGS21680 conjugate 5 inhibited aggregation of washed human platelets and was internalized. We envision that our multivalent dendrimer conjugates may improve overall pharmacological profiles compared to the monovalent GPCR ligands.
authors.affiliation: Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Kim
authors.forename: Béatrice
authors.initials: B
authors.lastname: Hechler
authors.forename: Athena M
authors.initials: AM
authors.lastname: Klutz
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
mesh_terms: D050091:Dendrimers; D011073:Polyamines / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D043562:Receptors, G-Protein-Coupled