共查询到20条相似文献,搜索用时 31 毫秒
1.
G. Cristalli M. Grifantini S. Vittori W. Balduini F. Cattabeni 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2)
Abstract A variety of adenosine analogues have been recently evaluated in order Lo find more potent and selective agonists on adenosine receptors. The most potent adenosine analogues acting on A1 receptor, a high affinity receptor inhibitory to adenylate cyclase, are N6-substituted compounds. So 6-cyclohexyladenosine (CHA) and 6-L-phenylisopropyladenosine (L-PIA) are extremely potent agonists on A2 receptor, whereas they are relatively weak agonists on A receptor, a lower affinity receptor which is stirnulatory to cyclase, and they have no effect on the adenosine P site. 相似文献
2.
《Journal of receptor and signal transduction research》2013,33(1-6):231-244
AbstractThe characteristics of adenosine receptors and adenosine uptake sites in brain are presented. High affinity adenosine receptors of the A1 type bind [3H]cyclohexyladenosine ([3H]CHA) and [3 H]diethyl-phenyl-xanthine ([3H]DPX) with 10?9 potency while adenosine uptake sites are labeled 10?10 potency with [3 H]nitrobenzyl-thioinosine ([3H]NBI). NBI does not inhibit either [3H]CHA (agonist) or [3H]DPX (antagonist) binding to adenosine receptors in brain cortical membranes and conversely CHA and other adenosine receptor ligands are very poor inhibitors of [3H]NBI binding to adenosine uptake sites. A number of other differences between the receptor and uptake site are discussed which provide rather strong evidence that these two sites are quite distinct and that the labeled ligands used represent specific probes for each site. 相似文献
3.
Gloria Cristalli Mario Grifantini Sauro Vittori Walter Balduini Flaminio Cattabeni 《Nucleosides, nucleotides & nucleic acids》2013,32(5):625-639
Abstract Several deaza-analogues of adenosine and 2-chloro-adenosine have been examined for their adenosine receptor affinity. It was found that the relative contribution of the nitrogen atoms of the purine moiety to binding at A1 rat brain adenosine receptor, follows the order N7 > N3 > N1. The affinity of the adenosine analogues for the adenosine rat brain receptor was besides compared with their activity as inhibitors of platelet aggregation. A synthesis of 2-chloro-1-deazaadenosine by two alternative routes starting from 7-nitroimidazo[4,5-b]pyridine-4-oxide is also reported. 相似文献
4.
Michael E. Perlman 《Nucleosides, nucleotides & nucleic acids》2013,32(1):73-82
Abstract The 2′-deuterio arabino analogs of tubercidin and adenosine have been prepared by Swern oxidation of the 3′,5′-TPDS derivatives of tubercidin and adenosine and reduction with NaBD4. Subsequent inversion of stereochemistry at C-2′ yielded [2′-2H]tubercidin and [2′-2H]adenosine with 98% deuterium incorporation. 相似文献
5.
Takeshi Wada Kiyoshi Inageda Keiichi Aritomo Ken-ichi Tokita Hiroshi Nishina Katsunobu Takahashi 《Nucleosides, nucleotides & nucleic acids》2013,32(6):1301-1314
Abstract Structure of cyclic adenosine diphosphoribose (cADPR) was reinvestigated by using 1H, 13C, and 31P NMR spectroscopy. The 1H-1H coupling constants and NOE data suggested that the adenosine and ribose moieties have a predominant C2′-endo conformation and an unusual flat conformation, respectively. 相似文献
6.
Yoshimitsu Yamazaki Hideo Suzuki Akira Kamibayashi Naoharu Watanabe Nobutaka Takahashi 《Bioscience, biotechnology, and biochemistry》2013,77(9):1945-1950
Five new derivatives of adenosine, N6-[(1-methylethyl)thiomethyl]-(1), N6-methyithiomethyl-(2), N6-phenylthiomethyl-(3), N6-[(3-amino-3-carboxypropyl)thiomethyl]-(4), and N6-[(2-amino-2-carboxyethyl)thiomethyl]adenosine (5), were synthesized and their cytokinin activity was tested in the Amaranthus betacyanin assay and the soybean callus growth.1, 2, and 3 were active in the former assay and all five compounds were active in the latter assay. The activities of the compounds were, however, weaker than those of the reference derivatives, in which Sulfides were replaced by methylenes, N6-isopentyl-, N6-n-propyl-, N6-benzyl-, and N6-(5-amino-5-carboxypentyl)adenosine. This fact indicates that the sulfide structure introduced into the N6-side chains had the effect of reducing cytokinin activity. 相似文献
7.
Michael F. Jarvis Michael Williams Un Hoi Do Matthew A. Sills 《Nucleosides, nucleotides & nucleic acids》2013,32(5):1201-1202
Abstract The use of xanthine adenosine receptor antagonists such as 1,3-dipropyl-8-phenylxanthine (DPX) as radioligands for the characterization of adenosine receptor Pharmacology have been limited by their high lipophilicity, low specific activity, and their general lack of selectivity and affinity for adenosine receptors. Recent attempts to address the technical problems associated with this class of compounds has resulted in the development of several xanthine derivatives (e.g. the functionalized xanthine congeners [3H]XCC and [3H]XAC2, and [3H]CPX3) which bind with high and selective affinity to the adenosine A1 receptor subtype. Based on efforts to optimize non-xanthine adenosine receptor antagonists, CGS 15943, a derivative of the pyrazoloquinazoline benzodiazepine receptor inverse agonist CGS 82165, represents the first reported non-xanthine structure that potently blocks adenosine receptors6. CGS 15943 has nanomolar affinity for both A1 and A2 receptor subtypes6. However, in contrast to many of the xanthine adenosine receptor antagonists, CGS 15943 is not a phosphodiesterase inhibitor and does not interact with adenosine transporter sites6. This compound is a potent and selective adenosine receptor antagonist in vivo 7 with a solubility/affinity ratio of greater than 10007. In the present studies, the binding of [3H]CGS 15943 to the adenosine A1 receptor was characterized. 相似文献
8.
Akihiro Imaeda Fumiaki Tomoike Mayu Hayakawa Kosuke Nakamoto Yasuaki Kimura Naoko Abe 《Nucleosides, nucleotides & nucleic acids》2013,32(12):972-979
AbstractsiRNA is a powerful method to suppress specific gene expression and has recently been utilized for molecular biology as well as medicine. However, introduction of dsRNA stimulates immune-responses as side-effects. In the present study, we utilized N6-methyl adenosine, one of the natural modified nucleosides, instead of adenosine in siRNA. When adenosine in the passenger or guide strand of siRNA was completely replaced with N6-methyl adenosine, the immune response against siRNA was evaded without any reduction in RNAi activity. This knowledge will promote the medical application of siRNA and enhance our understanding on cellular discrimination of non-self and self dsRNA. 相似文献
9.
M. Prescott A. G. McLennan D. C. Agathocleous P. C. Bulman Page R. Cosstick I. J. Galpin 《Nucleosides, nucleotides & nucleic acids》2013,32(2):297-303
Abstract Members of a series of α,ω-di(adenosin- N 6-yl)alkanes, comprising two adenosine residues linked with alkyl bridges from 1 to 14 methylene units in length, were found to be inhibitors of rat liver and BHK cell adenosine kinase. The inhibition was competitive with respect to adenosine and non-competitive with respect to ATP. The corresponding α,ω-di(cytidin-N 4-yl) alkanes were not inhibitors and N 6-alkyladenosines inhibited only weakly. 相似文献
10.
Gloria Cristalli Mario Grifantini Sauro Vittori Karl-Norbert Klotz Martin J. Lohse 《Nucleosides, nucleotides & nucleic acids》2013,32(2):213-222
Abstract The preparation of 2-azido-(R)-N6-p-hydroxyphenyl-isopropyladenosine (R-AHPIA) (1) starting from 2, 6-dichloro-9-(2, 3, 5 -tri-O-acetyl-β-D-ribofuranosyl) purine (2) is described. This new adenosine analogue exhibits patent agonist activity on A1 adenosine receptors and could be suitable for photoaffinity labeling studies on the same receptor subtype. 相似文献
11.
Heng T. Duong Zhan-Guo Gao Kenneth A. Jacobson 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1507-1517
Residues of the second extracellular loop are believed to be important for ligand recognition in adenosine receptors. Molecular modeling studies have suggested that one such residue, Gln 167 of the human A 3 receptor, is in proximity to the C2 moiety of some adenosine analogs when bound. Here this putative interaction was systematically explored using a neoceptor strategy, i.e., by site-directed mutagenesis and examination of the affinities of nucleosides modified to have complementary functionality. Gln 167 was mutated to Ala, Glu, and Arg, while the 2-position of several adenosine analogs was substituted with amine or carboxylic acid groups. All compounds tested lost affinity to the mutant receptors in comparison to the wild type. However, comparing affinities among the mutant receptors, several compounds bearing charge at the 2-position demonstrated preferential affinity for the mutant receptor bearing a residue of complementary charge. 13, with a positively-charged C2 moiety, displayed an 8.5-fold increase in affinity at the Q167E mutant receptor versus the Q167R mutant receptor. Preferential affinity for specific mutant receptors was also observed for 8 and 12. The data suggests that a direct contact is made between the C2 substituent of some charged ligands and the mutant receptor bearing the opposite charge at position 167. 相似文献
12.
Maria Grazia Zizzo Alessandra Bonomo Natale Belluardo Flavia Mulè Rosa Serio 《Life sciences》2009,84(21-22):772-778
AimsWe investigated the effects induced by exogenous adenosine on the spontaneous contractile activity of the longitudinal muscle of a mouse ileum, the receptor subtypes activated, the involvement of enteric nerves and whether opening of K+ channels was a downstream event leading to the observed effects.Main methodsMechanical responses of the mouse ileal longitudinal muscle to adenosine were examined in vitro as changes in isometric tension.Key findingsAdenosine caused a concentration-dependent reduction of the spontaneous contraction amplitude of the ileal longitudinal muscle up to its complete disappearance. This effect induced was markedly reduced by an A1 receptor antagonist, but not by A2 and A3 receptor antagonists and mimicked only by the A1 receptor agonist. Adenosine uptake inhibitors did not change adenosine potency. A1 receptor expression was detected at the smooth muscle level. Adenosine responses were insensitive to tetrodotoxin, atropine or nitric oxide synthase inhibitor. Tetraethylammonium and iberiotoxin, BKCa channel blockers, significantly reduced adenosine effects, whilst 4-aminopyridine, a Kv blocker, apamin, a small conductance Ca2+-activated K+ (SKCa) channel blocker, charybdotoxin, an intermediate conductance Ca2+-activated K+ (IKCa) and BKCa channel blocker, or glibenclamide, an ATP-sensitive K+ channel blocker, had no effects. The combination of apamin plus iberiotoxin caused a reduction of the purinergic effects greater than iberiotoxin alone.SignificanceAdenosine acts as an inhibitory modulator of the contractility of mouse ileal longitudinal muscle through postjunctional A1 receptors, which in turn would induce opening of BKCa and SKCa potassium channels. This study would provide new insight in the pharmacology of purinergic receptors involved in the modulation of the gastrointestinal contractility. 相似文献
13.
E. Lescrinier C. Pannecouque J. Rozenski A Van Aerschot L Kerremans P. Herdewijn 《Nucleosides, nucleotides & nucleic acids》2013,32(11-12):1863-1869
Abstract N 6-ablated adenosine can be synthesized by reduction of the corresponding carboxylic acid amides using Lm. Starting from 2′,3′-O-isopropylidene adenosine, N 6-ethyladenosine, N 6-propyladenosine, N 6-isobutyladenosine, N 6-benzyladenosine and N 6-furfuryladenosine were obtained in a three step procedure (acylation, reduction, deprotection). 相似文献
14.
Rubria Marlen Martínez-Casares Norberto Manjarrez Alvarez Aida Solís Oba Liliana Hernández Vázquez Alberto López-Luna 《Nucleosides, nucleotides & nucleic acids》2017,36(10):652-665
The separation of the diastereoisomers of the nucleoside derivatives of uridine, inosine and adenosine was performed by HPLC using chiral and no chiral columns, it was observed with the no chiral columns the resolution was good enough to determine diastereoisomeric excess. These methods were compared with 1H NMR, and no significant differences were observed between the three techniques. Diastereoisomeric uridine (3a), inosine (3b) and adenosine (4c) cyanohydrins were resolved by 1H nuclear magnetic resonance (1H NMR), chiral normal phase-high-performance liquid chromatography-diode array detector (NP-HPLC-DAD) and reversed phase (RP-HPLC-DAD); these methods allowed the assesment of the percent diastereoisomeric excess (% de) of the nucleosidic cyanohydrins of 3a (4, 6 and 4), 3b (10, 8 and 6) and 4c (4, 4 and 4). To the best of our knowledge, there are no reports using analytical techniques for the separation of the epimers of 3a, 3b and 4c. 相似文献
15.
《Journal of receptor and signal transduction research》2013,33(7-8):905-929
AbstractThe binding characteristics of radiolabeled N6-(cyclohexyl)adenosine ([3H]CHA), N6-(R-phenylisopropyl)adenosine ([3H]R-PIA), 5′-N-ethylcarboxamidoadenosine ([3H]NECA), and 2-[4-(2-carboxyethyl)phenyl]ethyl-amino-5′-N-ethylcarboxamidoadenosine ([3H]CGS 21680), to rat testis membranes were investigated. Specific binding of [3H]CGS 21680, a selective agonist for the A2a adenosine receptor, was very modest whilst the nonselective agonist [3H]NECA bound to rat testis membranes showing high binding capacity. At least two types of binding sites for [3H]NECA could be identified in rat testis membranes: high affinity sites and high capacity sites. Selective agonists for the At adenosine receptor, [3H]CHA and [3H]R-PIA bound with high affinity to a single class of binding sites. This high affinity binding site showed the typical pharmacological specificity of the A1 adenosine receptor with a potency order for agonists of CHA R-PIA > NECA > N6-(S-phenylisopropyl)adenosine (S-PIA). In order to detect the presence of the A3 adenosine receptor in these membranes we selectively blocked the A1 receptor with a large molar excess of a xanthine antagonist, either 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) or xanthine amine congener (XAC). In the presence of an antagonist a low affinity binding site for [3H]CHA and [3H]R-PIA was detected. This low affinity binding site showed a different pharmacological specificity than the high affinity binding site. In fact the potency order for agonists was CHA NECA = R-PIA > S-PIA. This finding suggests that the low affinity binding site represents the A3 adenosine receptor. 相似文献
16.
Abstract Lipid peroxidation induced by ascorbate inhibited [3H] adenosine binding to rat brain synaptosomes, probably via changes in polyunsaturated fatty acid composition. 相似文献
17.
M. L. Gonçalves F. Pinto J. A. Ribeiro 《Nucleosides, nucleotides & nucleic acids》2013,32(5):1161-1163
Abstract The effect of adenosine on 45Ca uptake by rat brain synaptosomes electrically stimulated was studied as function of time of stimulation (10, 30, 120 s). Inhibition of 45Ca uptake was more evident for 120 s. 相似文献
18.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):927-930
Abstract Synthesis of 2′-deoxy-2′-fluoro-N 6-substituted adenosines as bioisosteres of Cl-IB-MECA and their binding affinities to A3 adenosine receptor are described. 相似文献
19.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):923-925
Abstract Synthesis of 3′-deoxy-3′-fluoro-N 6-substituted adenosines as bioisosteres of Cl-IB-MECA and their binding affinities to A3 adenosine receptor are described. 相似文献
20.
Ashty Saleh Frans Compernolle Gerard Janssen 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):689-692
Abstract We report an improved synthesis of N 6-(6-aminohexyl)FAD (1) using an efficient one-pot conversion of inosine to the N-trifluoroacetyl protected N 6-(6-aminohexyl)adenosine 3. The 5′-O-phosphorylated AMP derivative 4, activated as the imidazolide, was coupled with commercial sodium riboflavin phosphate by using 18-crown-6 in DMF. 相似文献