Abstract
The 8-aza-immucillins (8-aza-9-deazapurines linked from C9 to C1 of 1,4-dideoxy-1,4-iminoribitol) have been designed as transition-state analogues of the reactions catalyzed by purine nucleoside phosphorylase and nucleoside hydrolases. Syntheses of the 8-aza-immucillin analogues of inosine and adenosine are described. They are powerful inhibitors of the target enzymes with equilibrium dissociation constants as low as 42 pM.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine / analogs & derivatives
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Adenosine / chemical synthesis
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Adenosine / chemistry
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Animals
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Aza Compounds / chemical synthesis*
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Aza Compounds / chemistry
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Cattle
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Crystallography, X-Ray
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Humans
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Inosine / analogs & derivatives
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Inosine / chemical synthesis
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Inosine / chemistry
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N-Glycosyl Hydrolases / antagonists & inhibitors
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Purine Nucleosides / chemical synthesis*
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Purine Nucleosides / chemistry
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Purine-Nucleoside Phosphorylase / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Aza Compounds
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Enzyme Inhibitors
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Purine Nucleosides
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Inosine
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Purine-Nucleoside Phosphorylase
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N-Glycosyl Hydrolases
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Adenosine