P. Suresh Jayasekara

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The nucleotide-sugar-activated P2Y14 receptor (P2Y14-R) is highly expressed in hematopoietic cells. Although the physiologic functions of this receptor remain undefined, it has been strongly implicated recently in immune and inflammatory responses. Lack of availability of receptor-selective high-affinity antagonists has impeded progress in studies of this(More)
The conventional route to alkoxyamine hydrochloride derivatives is by reaction of alkyl bromides with N-hydroxyphthalimide or N-hydroxysuccinimide followed by addition of hydrazine and HCl. Transformation of an alkyl bromide to the corresponding alkoxyamine hydrochloride can be accomplished more rapidly in high yield and without using hazardous hydrazine by(More)
5'-AMP-activated protein kinase (AMPK) and its pharmacological modulators have been targeted for treating type 2 diabetes. Extracellular uridine 5'-diphosphate (UDP) activates P2Y6 receptors (P2Y6Rs) in pancreatic β-cells to release insulin and reduce apoptosis, which would benefit diabetes. Here, we studied the role of P2Y6R in activation of AMPK in MIN6(More)
Interest is increasing in developing fluorescent ligands for characterization of adenosine receptors (ARs), which hold a promise of usefulness in the drug discovery process. The size of a strategically labeled AR ligand can be greatly increased after the attachment of a fluorophore. The choice of dye moiety (e.g. Alexa Fluor 488), attachment point and(More)
Extended N(4)-(3-arylpropyl)oxy derivatives of uridine-5'-triphosphate were synthesized and potently stimulated phospholipase C stimulation in astrocytoma cells expressing G protein-coupled human (h) P2Y receptors (P2YRs) activated by UTP (P2Y2/4R) or UDP (P2Y6R). The potent P2Y4R-selective N(4)-(3-phenylpropyl)oxy agonist was phenyl ring-substituted or(More)
4-Alkyloxyimino derivatives of pyrimidine nucleotides display high potency as agonists of certain G protein-coupled P2Y receptors (P2YRs). In an effort to functionalize a P2Y6R agonist for fluorescent labeling, we probed two positions (N(4) and γ-phosphate of cytidine derivatives) with various functional groups, including alkynes for click chemistry.(More)
S Activation of UTP-Sensitive P2Y2 Receptor Induces the Expression of Cholinergic Genes in Cultured Cortical Neurons: A Signaling Cascade Triggered by Ca Mobilization and Extracellular Regulated Kinase Phosphorylation Roy C. Y. Choi, Glanice K. Y. Chu, Nina L. Siow, Amanda W. Y. Yung, Lisa Y. Yung, Pinky S. C. Lee, Christopher C. W. Lo, Joseph Simon, Tina(More)
Extracellular nucleotides acting via P2 receptors play important roles in cardiovascular physiology/pathophysiology. Pyrimidine nucleotides activate four G protein-coupled P2Y receptors (P2YRs): P2Y2 and P2Y4 (UTP-activated), P2Y6, and P2Y14. Previously, we showed that uridine 5′-triphosphate (UTP) activating P2Y2R reduced infarct size and improved mouse(More)
Adenosine receptors (ARs) are members of the G protein-coupled receptor (GPCR) superfamily and have shown much promise as therapeutic targets. We have used an agonist-bound A2AAR X-ray crystallographic structure to design a chemically reactive agonist for site-specific chemical modification of the receptor. To further explore and chemically engineer its(More)
We establish structure activity relationships of extracellular nucleosides and nucleotides at G protein-coupled receptors (GPCRs), e.g. adenosine receptors (ARs) and P2Y receptors (P2YRs), respectively. We synthesize selective agents for use as pharmacological probes and potential therapeutic agents (e.g. A3AR agonists for neuropathic pain). Detailed(More)