title: 8-Aza-immucillins as transition-state analogue inhibitors of purine nucleoside phosphorylase and nucleoside hydrolases.
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.
authors.affiliation: Carbohydrate Chemistry, Industrial Research Limited, P.O. Box 31-310, Lower Hutt, New Zealand. g.evans@irl.cri.nz
authors.forename: Gary B
authors.initials: GB
authors.lastname: Evans
authors.forename: Richard H
authors.initials: RH
authors.lastname: Furneaux
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Gainsford
authors.forename: John C
authors.initials: JC
authors.lastname: Hanson
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Kicska
authors.forename: Antony A
authors.initials: AA
authors.lastname: Sauve
authors.forename: Vern L
authors.initials: VL
authors.lastname: Schramm
authors.forename: Peter C
authors.initials: PC
authors.lastname: Tyler
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002417:Cattle; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D007288:Inosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D001372:Aza Compounds; D004791:Enzyme Inhibitors; D011684:Purine Nucleosides; D007288:Inosine; D011683:Purine-Nucleoside Phosphorylase; D009699:N-Glycosyl Hydrolases; D000241:Adenosine