tailieunhanh - báo cáo khoa học: " Nucleoside conjugates of quantum dots for characterization of G protein-coupled receptors: strategies for immobilizing A2A adenosine receptor agonists"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Nucleoside conjugates of quantum dots for characterization of G protein-coupled receptors: strategies for immobilizing A2A adenosine receptor agonists | Das et al. Journal of Nanobiotechnology 2010 8 11 http content 8 1 11 RESEARCH JOURNAL OF NANOBIOTECHNOLOGY Open Access Nucleoside conjugates of quantum dots for characterization of G protein-coupled receptors strategies for immobilizing A2A adenosine receptor agonists Arijit Das Gangadhar J Sanjayan Miklós Kecskés Lena Yoo Zhan-Guo Gao and Kenneth A Jacobson 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 -V-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 UM . 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 .