Pseudofeedback Inhibition of Purine Synthesis by 6-Mercaptopurine Ribonucleotide and Other Purine Analogues

McCollister, Robert J.; Gilbert, Walter R.; Ashton, Doris M.; Wyngaarden, James Β.

doi:10.1016/s0021-9258(18)91353-0

Cited by 151 publications

(4 citation statements)

References 26 publications

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“…reports of nucleotide analogs that mimic natural regulatory nucleotides by activating or inhibiting regulatory enzymes. 6-Thioinosine 5 '-phosphate, 6-thioguanosine 5 '-phosphate, and 8-azaguanosine 5 '-phosphate inhibit phosphoribosyl pyrophosphate amidotransferase from pigeon liver (McCollister et al, 1964) and it has been proposed that these nucleotides are acting as analogs of the natural regulator GMP (Caskey et al, 1964).…”

Section: Discussionmentioning

confidence: 99%

Adenosine 5'-phosphorothioate. A nucleotide analog that is a substrate, competitive inhibitor, or regulator of some enzymes that interact with adenosine 5'-phosphate

Murray¹,

Atkinson²

1968

Biochemistry

138

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Adenosine 5 '-phosphorothioate, an analog of adenosine 5 '-phosphate, has been prepared from adenosine and thiophosphoryl chloride in triethyl phosphate in 65 % yield and isolated as the sodium salt. The adenosine 5 '-phosphate content of this product (measured with adenylate kinase) was less than 0.5% and the content of adenosine derivatives other than the 5'phosphorothioate (measured as unchanged material after treatment with adenylate deaminase or with 5'nucleotidase) was 1-3 %. Adenosine 5 '-phosphorothioate (0.34 mM) was phosphorylated by adenosine triphosphate in the presence of muscle adenylate kinase at less than 0.3% of the rate with adenosine 5'-phosphate at the same concentration, but 0.25 mM adenosine 5 '-phosphorothioate increased the adenosine 5 '-phosphate concentration for half-maximal activity, [SI, 5 , from 0.15 to 0.18 mM and decreased the maximal velocity (V, micromoles per minute per milligram of protein) from 120 to 91 without changing the slope (1.35) of the Hill plot. Adenosine 5 '-phosphorothioate was deaminated by adenylate deaminase from rat skeletal muscle. The Michaelis constant, K,, was 1.6 mM and V was 125, 9% of the maximal velocity with adenosine 5'-phosphate(V = 1330; K, = 0.9 mM). With 5'-nucleotidase from Crotalus venom liberation of adenosine from adenosine 5 '-phosphorothioate was much slower than that from adenosine 5 '-phosphate (V = 0.026 and 1.39, respectively) but K, for adenosine 5'-phosphorothioate N ucleoside 5 '-monophosphates and nucleoside 5 '-triphosphates, particularly AMP and ATP, are some of the most important regulators of metabolic processes (for reviews, see Krebs (1964) and Atkinson (1966)).

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Section: Discussionmentioning

confidence: 99%

Adenosine 5'-phosphorothioate. A nucleotide analog that is a substrate, competitive inhibitor, or regulator of some enzymes that interact with adenosine 5'-phosphate

Murray¹,

Atkinson²

1968

Biochemistry

138

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“…Purine-like inhibitors acting at the hydroxypurine site, like allopurinol, have also been designed . However, they can have the undesirable effect of interfering with other aspects of purine metabolism . Knowledge of the molecular interactions that modulate the binding to the purine site would be very helpful in the design of potent, specific inhibitors lacking secondary effects.…”

Section: Introductionmentioning

confidence: 99%

Tautomerism of Xanthine Oxidase Substrates Hypoxanthine and Allopurinol

1996

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The tautomerism of neutral hypoxanthine and allopurinol in the gas phase and in aqueous solution has been examined by theoretical methods. The tautomeric equilibrium in the gas phase was studied from semiempirical and ab initio quantum mechanics (QM) and also from density functional theory (DFT) calculations. Electron correlation effects were included in ab initio computations at the Møller−Plesset level, and DFT calculations were carried out using the Becke3−Lee−Yang−Parr functional. The influence of the solvent was examined from self-consistent reaction field calculations performed with different continuum models. The results provide a detailed picture of the tautomerism of these biologically relevant compounds. Comparison with available experimental data provides support for the quality of results derived from theoretical computations. Inspection of the most stable tautomeric forms allows discussion of the functional implications of tautomerism for recognition and binding of these molecules to xanthine oxidase.

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“…In a non-matching control group, transaminases fell rapidly in those patients treated with azathioprine (in two to four weeks), but the difference after three months was no longer statistically significant. In serial biopsy tests on 27 patients there were nine who had improvement, 12 tratados a lo largo de 3 a 12 meses con azatioprina (Imuran, Imurel®); la dosis inicial alcanzó 150 mg/d, la de mantenimiento 50-100 mg/d. La elevada actividad de las transaminasas séricas GOT y GPT remitió en 35 pacientes, siguió inalterada en otros 16 y siguió elevándose en S casos.…”

Section: Ergebnisseunclassified

Die Behandlung der chronischen Hepatitis mit immunsuppressiven Substanzen

Kommerell¹,

Seeliger²

1970

Dtsch med Wochenschr

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Die Behandlung der chronischen Hepatitis mit immunsuppressiven Substanzen 56 Patienten mit bioptisch gesicherter chronischer Hepatitis wurden drei bis zwölf Monate lang mit Azathioprin (Imuran®, Imurel®) behandelt; die Anfangsdosis betrug 150 mg/d, die Erhaltungsdosis 50-100 mg/d. Die erhöhte Aktivität der Serumtransaminasen GOT und GPT ging bei 35 Patienten zurück, bei 16 blieb sie unverändert, und in fünf Fällen stieg sie weiter an. Gegenüber einer nicht korrelierten Vergleichsgruppe ergab sich, daß die Transaminasen bei den mit Azathioprin behandelten Patienten zwar rasch, in zwei bis vier Wochen, abfielen, die Unterschiede aber nach einem Vierteljahr nicht mehr signifikant waren. Bei bioptischen Verlaufskontrollen von 27 Patienten zeigte sich in neun Fällen eine Besserung, in zwölf Fällen keine Veränderung und bei sechs Kranken eine Verschlechterung des histologischen Befundes. Die histologischen Ergebnisse lassen im Gegensatz

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Pseudofeedback Inhibition of Purine Synthesis by 6-Mercaptopurine Ribonucleotide and Other Purine Analogues

Cited by 151 publications

References 26 publications

Adenosine 5'-phosphorothioate. A nucleotide analog that is a substrate, competitive inhibitor, or regulator of some enzymes that interact with adenosine 5'-phosphate

Adenosine 5'-phosphorothioate. A nucleotide analog that is a substrate, competitive inhibitor, or regulator of some enzymes that interact with adenosine 5'-phosphate

Tautomerism of Xanthine Oxidase Substrates Hypoxanthine and Allopurinol

Die Behandlung der chronischen Hepatitis mit immunsuppressiven Substanzen

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