Synthesis of 9-(3,4-dioxopentyl)hypoxanthine, the first arginine-directed purine derivative: an irreversible inactivator for purine nucleoside phosphorylase
| العنوان: | Synthesis of 9-(3,4-dioxopentyl)hypoxanthine, the first arginine-directed purine derivative: an irreversible inactivator for purine nucleoside phosphorylase |
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| المؤلفون: | Salvatore J. Salamone, Frank Jordan |
| المصدر: | Biochemistry. 21:6383-6388 |
| بيانات النشر: | American Chemical Society (ACS), 1982. |
| سنة النشر: | 1982 |
| مصطلحات موضوعية: | Purine, chemistry.chemical_classification, Time Factors, biology, Stereochemistry, Affinity label, Purine analogue, Purine nucleoside phosphorylase, Biochemistry, chemistry.chemical_compound, Adenosine deaminase, Purine-Nucleoside Phosphorylase, chemistry, Hypoxanthines, medicine, biology.protein, Nucleotide, Pentosyltransferases, Inosine, Mathematics, Hypoxanthine, medicine.drug |
| الوصف: | The synthesis of two potential arginine-directed purine-based analogues, 6-chloro-9-(3,4-dioxopentyl)purine (6) and 9-(3,4-dioxopentyl)hypoxanthine (7), is reported. Compound 7 was extensively tested as a potential affinity label of purine nucleoside phosphorylase (EC 2.4.2.1) from human erythrocytes. Evidence that 7 reacted with the catalytic center of purine nucleoside phosphorylase includes the following: (1) time-dependent inactivation of the enzyme by 7 was observed; (2) a plot of the pseudo-first-order rate constant for inactivation of the enzyme vs. concentration of 7 was hyperbolic, characteristic of saturation phenomenon; (3) substrates (Pi, arsenate, inosine) and a competitive inhibitor (formycin B) protected the enzyme from inactivation by 7. Compound 7 was 25 times more effective in inhibiting purine nucleoside phosphorylase than butanedione. Evidence that 7 modified arginine(s) includes the following: (1) when the inactivation was performed in borate, both the rate and the extent of inactivation were enhanced compared to those of the controls run in tris(hydroxymethyl)aminomethane hydrochloride (Tris-HCl) buffer; (2) dialysis of inactivator reversed the inactivation in Tris-HCl but not in borate buffer. All the above evidence combined with the previous demonstration [Jordan, F., & Wu, A. (1978) Arch. Biochem. Biophys. 190, 699-704] that butanedione modified only arginines in purine nucleoside phosphorylases and the results presented here demonstrating the similarities in the behavior of butanedione and 7 imply that compound 7 can be called an arginine-directed affinity label for purine nucleoside phosphorylase. |
| تدمد: | 1520-4995 0006-2960 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::20f0b4e318c845a5842ae9f4cd8eb7be https://doi.org/10.1021/bi00268a010 |
| رقم الأكسشن: | edsair.doi.dedup.....20f0b4e318c845a5842ae9f4cd8eb7be |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204995 00062960 |
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