8-Aza-immucillins as transition-state analogue inhibitors of purine nucleoside phosphorylase and nucleoside hydrolases

Gary B. Evans; Richard H. Furneaux; Graeme J. Gainsford; John C. Hanson; Gregory A. Kicska; Antony A. Sauve; Vern L. Schramm; Peter C. Tyler

doi:10.1021/jm0203332

8-Aza-immucillins as transition-state analogue inhibitors of purine nucleoside phosphorylase and nucleoside hydrolases

Gary B. Evans, Richard H. Furneaux, Graeme J. Gainsford, John C. Hanson, Gregory A. Kicska, Antony A. Sauve, Vern L. Schramm, Peter C. Tyler

Biochemistry

Research output: Contribution to journal › Article › peer-review

60 Scopus citations

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.

Original language	English (US)
Pages (from-to)	155-160
Number of pages	6
Journal	Journal of Medicinal Chemistry
Volume	46
Issue number	1
DOIs	https://doi.org/10.1021/jm0203332
State	Published - Jan 2 2003

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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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.",

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AU - Evans, Gary B.

AU - Furneaux, Richard H.

AU - Gainsford, Graeme J.

AU - Hanson, John C.

AU - Kicska, Gregory A.

AU - Sauve, Antony A.

AU - Schramm, Vern L.

AU - Tyler, Peter C.

PY - 2003/1/2

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AB - 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.

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8-Aza-immucillins as transition-state analogue inhibitors of purine nucleoside phosphorylase and nucleoside hydrolases

Abstract

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