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Adenosine Analogues (adenosine + analogue)

Distribution by Scientific Domains

Chemistry	50%

Selected Abstracts

Stabilisation of RNA Bulges by Oligonucleotide Complements Containing an Adenosine Analogue

CHEMBIOCHEM, Issue 11 2003
Annemieke Madder
Abstract Incorporation of 2,-deoxy-2,- , -(1-naphthylmethyl)tubercidin into an oligodeoxyribonucleotide mostly has little or a slightly negative effect on the Tmvalues of complexes with DNA complements. With the same naphthylmethyl-substituted nucleoside at the 3,-end of a 2,-O-methyloligoribonucleotide, however, a stabilisation of 1,2,°C in the corresponding complexes with both DNA and RNA is observed. When the target sequence is an RNA fragment forming a two- or three-nucleotide bulge, complexes with (naphthylmethyl)tubercidin-modified oligodeoxyribonucleotides, as well as with the corresponding 2,-O-methyloligoribonucleotides, give stabilisations of 1,2,°C for the three-nucleotide bulge and of almost 4,°C for the two-nucleotide bulge. This stabilisation is specific to RNA, since the corresponding complexes with the DNA fragments do not display this effect. Thus, the (naphthylmethyl)tubercidin-containing oligonucleotides are the first reported oligonucleotide modifications that specifically stabilise bulged RNA. [source]

Electrocatalytic Oxidation of NADH by Oxidized s-Adenosyl-L-Methionine (SAMe): Application to NADH and SAMe Determinations

ELECTROANALYSIS, Issue 11 2004
Noemí de-los-Santos-Álvarez
Abstract s -Adenosyl- L -methionine (SAMe) is an adenosine analogue with therapeutical activity against affective disorders and liver dysfunctions. It can be oxidized on graphite electrode yielding a strongly adsorbed electroactive oxidation product for which a quinone-imine structure is proposed. This compound is capable of electrocatalyzing the NADH oxidation at low potentials, lowering the overvoltage by about 300,mV. An amperometric method for NADH determination at +0.1,V (Ag|AgCl|KClsat) is developed using an oxidized-SAMe-modified electrode in pH,9. Linear calibration plots were obtained with a detection limit of 2.4,nM. The electrode response time and the relative standard deviation of the slope of the calibration plot for 5 different modified electrodes were 12,s and 5.6% respectively. The catalytic scheme also provides the first method to determine SAMe itself by adsorptive differential pulse voltammetry. The linear range was found to be 42.4,424,nM with a reproducibility of 6.9%. The method was applied to SAMe determination in a pharmaceutical formulation. [source]

Adenosine A1 receptors and vascular reactivity

ACTA PHYSIOLOGICA, Issue 2 2010
Y. Wang
Abstract Aim:, Blood pressure is higher in A1 receptor knock-out (A1R,/,) mice than in wild type litter mates (A1R+/+) and we have examined if this could be related to altered vascular functions. Methods:, Contraction of aortic rings and mesenteric arteries were examined. To examine if the adenosine A1 receptor-mediated contraction of aortic muscle was functionally important we examined pulse pressure (PP) and augmentation index (AIX) using a sensor that allows measurements of rapid pressure transients. Results:, Contraction of aortic rings to phenylephrine and relaxation to acetylcholine were similar between genotypes. The non-selective adenosine receptor agonist N -ethyl carboxamido adenosine (NECA) enhanced the contractile response, and this was eliminated in aortas from A1R,/, mice. However, in mesenteric arteries no contractile response was seen and adenosine-mediated relaxation was identical between studied genotypes. A2B adenosine receptors, rather than A2A receptors, may be mainly responsible for the vasorelaxation induced by adenosine analogues in the examined mouse vessels. PP was higher in A1R,/, mice, but variability was unaltered. AIX was not different between genotypes, but the NECA-induced fall was larger in A1R,/, mice. Conclusions:, The role of adenosine A1 receptors in regulating vessel tone differs between blood vessels. Furthermore, contractile effects on isolated vessels cannot explain the blood pressure in A1 knock-out mice. The A1 receptor modulation of blood pressure is therefore mainly related to extravascular factors. [source]

In vitro induction of T cells that are resistant to A2 adenosine receptor-mediated immunosuppression

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2009
Akio Ohta
Background and purpose:, The increased levels of extracellular adenosine in inflamed tissues down-regulate activated immune cells via the A2A adenosine receptor. This A2A adenosine receptor-mediated immunosuppression is a disqualifying obstacle in cancer immunotherapy as it protects cancerous tissues from adoptively transferred anti-tumour T cells. The aim of this study was to test whether the negative selection of T cells will produce T cells that are resistant to inhibition by extracellular adenosine. Experimental approach:, Cytotoxic T lymphocytes (CTL) were developed by mixed lymphocyte culture in the presence or absence of the adenosine receptor agonist 5,-N-ethylcarboxamidoadenosine (NECA). The sensitivity of CTL to adenosine analogues was characterized by cAMP induction, interferon-, production and cytotoxicity. Key results:, CTL that could proliferate even in the presence of NECA were less susceptible to inhibition by A2A adenosine receptor agonists, as shown by a much smaller accumulation of cAMP and less inhibition of interferon-, production compared with control CTL. The successful protocol to produce CTL that are both resistant to adenosine-mediated immunosuppression and maintain strong cytotoxicity and interferon-, secretion required NECA to be added only during the expansion stage after the establishment of CTL. In contrast, the priming of resting T cells in the presence of NECA resulted in T cells with impaired effector functions. Conclusions and implications:, Adenosine-resistant effector T cells were successfully obtained by exposure of activated T cells to NECA. These in vitro studies form the basis for future attempts to produce anti-tumour T cells that are more effective in adoptive immunotherapy. [source]