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- Title
Nucleoside conjugates of quantum dots for characterization of G protein-coupled receptors: strategies for immobilizing A<sub>2A</sub> adenosine receptor agonists.
- Authors
Das, Arijit; Sanjayan, Gangadhar J.; Kecskés, Miklós; Lena Yoo; Zhan-Guo Gao; Jacobson, Kenneth A.
- Abstract
Background: Quantum dots (QDs) are crystalline nanoparticles that are compatible with biological systems to provide a chemically and photochemically stable fluorescent label. New ligand probes with fluorescent reporter groups are needed for detection and characterization of G protein-coupled receptors (GPCRs). Results: Synthetic strategies for coupling the A2A adenosine receptor (AR) agonist CGS21680 (2-[4-(2- carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine) to functionalized QDs were explored. Conjugates tethered through amide-linked chains and poly(ethyleneglycol) (PEG) displayed low solubility and lacked receptor affinity. The anchor to the dendron was either through two thiol groups of (R)-thioctic acid or through amide formation to a commercial carboxy-derivatized QD. The most effective approach was to use polyamidoamine (PAMAM) D5 dendrons as multivalent spacer groups, grafted on the QD surface through a thioctic acid moiety. In radioligand binding assays, dendron nucleoside conjugate 11 displayed a moderate affinity at the human A2AAR (Kiapp 1.02 ± 0.15 μM). The QD conjugate of increased water solubility 13, resulting from the anchoring of this dendron derivative, interacted with the receptor with Kiapp of 118 ± 54 nM. The fluorescence emission of 13 occurred at 565 nm, and the presence of the pendant nucleoside did not appreciably quench the fluorescence. Conclusions: This is a feasibility study to demonstrate a means of conjugating to a QD a small molecular pharmacophore of a GPCR that is relatively hydrophobic. Further enhancement of affinity by altering the pharmacophore or the linking structures will be needed to make useful affinity probes.
- Subjects
QUANTUM dots; NANOPARTICLES; BIOLOGICAL systems; CELL receptors; LIPOIC acid
- Publication
Journal of Nanobiotechnology, 2010, Vol 8, p11
- ISSN
1477-3155
- Publication type
Article
- DOI
10.1186/1477-3155-8-11