Third-Generation Immucillins: Syntheses and Bioactivities of Acyclic Immucillin Inhibitors of Human Purine Nucleoside Phosphorylase
نویسندگان
چکیده
منابع مشابه
Nucleotide analogue inhibitors of purine nucleoside phosphorylase.
The diphosphate of the antiherpetic agent acyclovir [9-[(2-hydroxyethoxy)methyl]guanine] has been shown to inhibit purine nucleoside phosphorylase with unique potency (Tuttle, J. V., and Krenitsky, T. A. (1984) J. Biol. Chem. 259, 4065-4069). A major factor contributing to the superior inhibition by this diphosphate over the corresponding mono- and triphosphates is revealed here. Homologues of ...
متن کاملPurine Nucleoside Phosphorylase
Purine nucleoside phosphorylase (EC 2.4.2.1) from bovine spleen is a trimeric enzyme that readily dissociates to the monomer. Dilution of enzyme from 20 to 0.02 pg of protein/ml is accompanied by a greater than 50-fold increase in the specific activity (utrimer = 0.23 nmol/min/pg; umonomer = 12.5 nmol/min/pg). Gel permeation chromatography in the presence of the substrate phosphate shows the en...
متن کاملPurine nucleoside phosphorylase from human erythrocytes.
Purine nucleoside phosphorylase has been purified about 7,300-fold and crystallized from human erythrocytes (mol wt 81,000). The recrystallized enzyme exists in the form of needles and sometimes bundles of needles and has a specific activity of 96 pM units per mg of protein. A number of phenomena reported earlier for a less pure preparation of this enzyme are still seen with the crystalline enz...
متن کاملImmucillin H, a powerful transition-state analog inhibitor of purine nucleoside phosphorylase, selectively inhibits human T lymphocytes.
Transition-state theory has led to the design of Immucillin-H (Imm-H), a picomolar inhibitor of purine nucleoside phosphorylase (PNP). In humans, PNP is the only route for degradation of deoxyguanosine, and genetic deficiency of this enzyme leads to profound T cell-mediated immunosuppression. This study reports the biological effects and mechanism of action of Imm-H on malignant T cell lines an...
متن کاملOne-third-the-sites transition-state inhibitors for purine nucleoside phosphorylase.
Genetic defects in human purine nucleoside phosphorylase cause T-cell deficiency as the major phenotype. It has been proposed that efficient inhibitors of the enzyme might intervene in disorders of T-cell function. Compounds with features of the transition-state structure of purine nucleoside phosphorylase were synthesized and tested as inhibitors. The transition-state structure for purine nucl...
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ژورنال
عنوان ژورنال: Journal of Medicinal Chemistry
سال: 2009
ISSN: 0022-2623,1520-4804
DOI: 10.1021/jm801421q