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Title:
Structure–activity relationships of dinucleotides: Potent and selective agonists of P2Y receptors | Purinergic Signalling
Description:
Dinucleoside polyphosphates act as agonists on purinergic P2Y receptors to mediate a variety of cellular processes. Symmetrical, naturally occurring purine dinucleotides are found in most living cells and their actions are generally known. Unsymmetrical purine dinucleotides and all pyrimidine containing dinucleotides, however, are not as common and therefore their actions are not well understood. To carry out a thorough examination of the activities and specificities of these dinucleotides, a robust method of synthesis was developed to allow manipulation of either nucleoside of the dinucleotide as well as the phosphate chain lengths. Adenosine containing dinucleotides exhibit some level of activity on P2Y1 while uridine containing dinucleotides have some level of agonist response on P2Y2 and P2Y6. The length of the linking phosphate chain determines a different specificity; diphosphates are most accurately mimicked by dinucleoside triphosphates and triphosphates most resemble dinucleoside tetraphosphates. The pharmacological activities and relative metabolic stabilities of these dinucleotides are reported with their potential therapeutic applications being discussed.
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Keywords {🔍}
nmr, dinucleotides, article, google, scholar, cas, dinucleoside, pubmed, receptor, synthesis, activity, cells, diadenosine, receptors, uridine, polyphosphates, triphosphates, tetraphosphate, water, reaction, full, phosphate, adenosine, symmetrical, nucleoside, agonist, tetraphosphates, human, figure, hplc, agonists, nucleotide, min, data, dinucleotide, upu, nucleotides, size, give, mononucleotides, mmol, access, compounds, monophosphate, stability, salt, diuridine, buffer, dissolved, uch,
Topics {✒️}
ligand-gated ion channels 6-diaminopurine β-d-ribofuranoside p1 reversed-phase paired-ion hplc potential anti-platelet-aggregation agents wild-type 1321n1 cell cyclic meta-triphosphate intermediate article download pdf full size image gibco-brl life technologies hamilton prp-x100 column nitric oxide release purified lysyl-srna synthetase glucuronidation-resistant mad analogue structure–activity relationships cyclic meta-triphosphate purinergic p2y receptors purinergic signalling 1 research triangle park related subjects phosphate chain lengths privacy choices/manage cookies cyclic uridine 5′-trimetaphosphate naturally occurring compounds total nucleotide content tissue culture facility leucyl-trna synthetase ribosomal peptide synthetases bronchial epithelial cells dinucleoside tetraphosphate synthetase relative metabolic stabilities facilitating neurotransmitter release manipulate selectivity based columbus plate washer secretagogue-induced release p2y receptor subtype phosphate chain length dynamic synthetic methods synthetic methods existed inosine 5′-monophosphate dehydrogenase inosine monophosphate dehydrogenase bovine adrenal medulla resemble dinucleoside tetraphosphates dinucleoside tetraphosphates mimic anion exchange hplc human nervous system intracellular ca2+ measurements intracellular ca2+ levels extracellular lactate dehydrogenase p2y receptor activity human clinical trials
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headline:Structure–activity relationships of dinucleotides: Potent and selective agonists of P2Y receptors
description:Dinucleoside polyphosphates act as agonists on purinergic P2Y receptors to mediate a variety of cellular processes. Symmetrical, naturally occurring purine dinucleotides are found in most living cells and their actions are generally known. Unsymmetrical purine dinucleotides and all pyrimidine containing dinucleotides, however, are not as common and therefore their actions are not well understood. To carry out a thorough examination of the activities and specificities of these dinucleotides, a robust method of synthesis was developed to allow manipulation of either nucleoside of the dinucleotide as well as the phosphate chain lengths. Adenosine containing dinucleotides exhibit some level of activity on P2Y1 while uridine containing dinucleotides have some level of agonist response on P2Y2 and P2Y6. The length of the linking phosphate chain determines a different specificity; diphosphates are most accurately mimicked by dinucleoside triphosphates and triphosphates most resemble dinucleoside tetraphosphates. The pharmacological activities and relative metabolic stabilities of these dinucleotides are reported with their potential therapeutic applications being discussed.
datePublished:2005-03-07T00:00:00Z
dateModified:2005-03-07T00:00:00Z
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IC50
metabolic stability
P2Y receptors
receptor selectivity
synthesis of dinucleotides
Biomedicine
general
Pharmacology/Toxicology
Human Physiology
Neurosciences
Cancer Research
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headline:Structure–activity relationships of dinucleotides: Potent and selective agonists of P2Y receptors
description:Dinucleoside polyphosphates act as agonists on purinergic P2Y receptors to mediate a variety of cellular processes. Symmetrical, naturally occurring purine dinucleotides are found in most living cells and their actions are generally known. Unsymmetrical purine dinucleotides and all pyrimidine containing dinucleotides, however, are not as common and therefore their actions are not well understood. To carry out a thorough examination of the activities and specificities of these dinucleotides, a robust method of synthesis was developed to allow manipulation of either nucleoside of the dinucleotide as well as the phosphate chain lengths. Adenosine containing dinucleotides exhibit some level of activity on P2Y1 while uridine containing dinucleotides have some level of agonist response on P2Y2 and P2Y6. The length of the linking phosphate chain determines a different specificity; diphosphates are most accurately mimicked by dinucleoside triphosphates and triphosphates most resemble dinucleoside tetraphosphates. The pharmacological activities and relative metabolic stabilities of these dinucleotides are reported with their potential therapeutic applications being discussed.
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dinucleoside polyphosphates
IC50
metabolic stability
P2Y receptors
receptor selectivity
synthesis of dinucleotides
Biomedicine
general
Pharmacology/Toxicology
Human Physiology
Neurosciences
Cancer Research
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