Immucillin H, a powerful transition-state analog inhibitor of purine nucleoside phosphorylase, selectively inhibits human T lymphocytes
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چکیده
منابع مشابه
Immucillin 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...
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Purine nucleoside phosphorylase (PNP; EC: 2.4.2.1) is a key enzyme involved in the purine salvage pathway. A recent bioinformatic study by Yadav, P. K. et al. (Bioinformation 2012, 8(14), 664-672) reports PNP as an essential enzyme and potential drug target in community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). We conducted an analysis using the methodology outlined by the...
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The discovery of purine nucleoside phosphorylase (PNP) deficiency and T lymphocytopenia suggested that inhibition of this enzyme could serve as a therapeutic target. Inhibitors of PNP failed until structure-based synthesis of immucillin-H (BCX-1777, forodesine), a transition-state analog of PNP. The picomolar potency for PNP, T cell-selective cytotoxicity, and animal studies provided the ration...
متن کاملDevelopment of transition state analogues of purine nucleoside phosphorylase as anti-T-cell agents.
Newborns with a genetic deficiency of purine nucleoside phosphorylase (PNP) are normal, but exhibit a specific T-cell immunodeficiency during the first years of development. All other cell and organ systems remain functional. The biological significance of human PNP is degradation of deoxyguanosine, and apoptosis of T-cells occurs as a consequence of the accumulation of deoxyguanosine in the ci...
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ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 2001
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.071050798