Toward multivalent signaling across G protein-coupled receptors from poly(amidoamine) dendrimers.
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.
Kim
Yoonkyung
Y
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hechler
Béatrice
B
Klutz
Athena M
AM
Gachet
Christian
C
Jacobson
Kenneth A
KA
D050091:Dendrimers; D011073:Polyamines / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D043562:Receptors, G-Protein-Coupled