Xanthine-7-ribosides

Figure 2. Chemical structures of adenosine (left), xanthines (middle) and xanthine-7-ribosides (right) used in this study.

Subsequently, we synthesized the 7-ribosides of theophylline, 1,3-dipropylxanthine and 1,3-dibutylxanthine [46]. The Kj values at 25 °C of the three xanthines, the corresponding xanthine-7-ribosides and the reference full agonist R-PIA were obtained in radioligand binding studies with the tritiated agonist N -cyclohexyladenosine (CHA) on rat brain membranes. The results are summarized in Table 1. 

Thermodynamic equilibrium parameters for displacement of [ H]CHA by xanthines, xanthine-7-ribosides and R-PIA. Results are from three independent experiments performed in duplicate. AG°, AH° and AS° values were calculated from Kj values (S.E.M. 

Figure 3. Van t Hoff plots showing the effect of temperature on the equilibrium association constants, K, of both xanthines ( theophylline 1,3-dipropylxanthine x 1,3-dibutylxanthine) and xanthine-7-ribosides ( theophylline-7-riboside O 1,3-dipropyl-xanthine-7-riboside a 1,3-dibutylxanthine-7-riboside). All plots were essentially linear (r > 0.95). Reproduced with permission of principal author and publisher of ref. [34].

Xanthine, AD97 Xanthine riboside, AR8l Xanthopterin, AG62 Xanthosine, AR8l o-Xylene, AN32 m-Xylene, AN33 -Xylene, AN3 ... 

Figure 9.99 Separation of the components of the reaction studied (catalysis by nucleoside phosphorylase of a purine riboside-base conversion) by HPLC. Chromatographic conditions isocratic elution flow rate, 2 mL/min 0.02 F KH2P04 (pH 4.2) and 3% methanol. Peaks 1, uric acid 2, hypoxanthine 3, xanthine 4, inosine. (From Halfpenny and Brown, 1980.)...

Allopurinol has been used for 16 years at doses ranging from 200 to 800 mg/day for the control of primary and secondary hyperuricemia. At the most commonly used doses of allopurinol (300-400 mg/ day) about 70% of the allopurinol is oxidized to oxipurinol, which is excreted in the urine. Urinary allopurinol and allopurinol riboside each account for about 10% of the dose. Since the degree of xanthine oxidase inhibition is dose-related, not only the oxidation of hypoxanthine and xanthine to uric acid, but also the oxidation of allopurinol to oxipurinol might be expected to be strongly inhibited at high doses of allopurinol. This would lead to increased levels of allopurinol, as well as allopurinol riboside, in plasma and urine. The extent to which this phenomenon occurs was investigated in several laboratory animal species and in man. 

Uric acid, hypoxanthine, xanthine, allopurinol, oxi-purinol and allopurinol-1-riboside by a modification of the method of Webster et al. on a Chrompack RP-8 column. Urine samples were preseparated on anion-exchange columns. For the determination of oxipurinol-7-riboside a preextraction of ribosides on Bio-Rad Affi-Gel 601 was necessary. For the determination of adenine the mobile phase contained 20% of methanol and was adjusted to pH 5.5. ... 

The inhibitory effect of allopurinol on the first three steps of purine biosynthesis in Neurospora crassa cultures could be due 1. to the formation of allopurin-ol-l-ribonucleotide (by HGPRTase 1,19 nMol/mg protein/ hr in our Neurospora crassa cultures) 2. due to an oxipurinol-7-ribonucleotide effect, namely the formation of oxipurinol (by xanthine oxidase) and then oxipurinol-7-ribonucleotide (by OPRTase) and 3. by formation of allopurinol-1-ribotide through allopurin-ol-1-riboside (by a purine nucleoside phosphorylase) to allopurinol-1-ribonucleotide (by a nucleoside kinase). This latter pathway seems rather improbable because we could not demonstrate an effect on purine biosynthesis by direct addition of allopurinol-1-ribonucleoside to the incubation medium. Allopurinol-1-ribonucleotide inhibits significantly at higher concentrations. This is to explain if there is free access of the ribonucleotide form through the cell membrane (at least in these high concentrations) or if there is conversion to the ribonucleoside (which then enters the cell) by a nucleotidase located on the cell membrane. This latter mechanism however seems more improbable bcause there was no effect by allopurinol-1-ribonucleoside (which excludes the possibility for subsequent formation of allopurinol-1 -ribonucleotide by a nucleoside kinase, at least... 

Allopurinol was given orally up to fifty times maximum human therapeutic doses without side effects. Allopurinol and oxipuri-nol appeared to be handled similarly by pig (798) and human kidney (in contrast to rat, mouse and dog) (9) Xanthine oxidase was maximally inhibited by allopurinol at 2.2 mmol (300 mg)/kg/day with no further increase in oxipurinol and xanthine excretion at higher doses. No limit, however, was found for the rmation of allopurinol riboside. 9k% of radioactivity om (6- C) allopurinol was recovered from the urine and no C incorporation was detected in tissue nucleotides. 

II) can markedly promote shoot regeneration, whereas xanthine (IV) does not. Auxin, on the other hand, promotes root regeneration. Similar results were found by several other authors - . There are, however, certain differences among the different materials, since, for instance, oxidized purines (IV, V), pyrimidines (VI, VII) or purine ribosides (X) were sometimes effective, sometimes not. 

Thin-layer chromatography is no longer in use on a large scale, but may be helpful in isolated cases such as adenylosuccinase deficiency [3]. The diazo reagent not only stains with succinyl aminoimidazole carboxamide riboside (SAICAR), but also with xanthine and guanine. 

McLaren (60), uang the minimal medium of Yaw supplemented with methionine and histidine (57), obtained an increase in flavin yidd of 66% with adenine and 26%with dther guanine or xanthine. Similar results were obtained by McNutt (61) with the same medium, and by Brawn et al. (68) and Goodwin and P idlington (62) under somewhat different conditions. The corresponding purine ribosides are not superior to the free bases (62, 61). It is notewortiiy, however, that neither Yaw (87) nor Minoura (62) obtained stimulation of flavin syntheds by nuddc add hydrolyzates or selected purine bases intact nudeic add was effective under Minoura s... 

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