title: Exploring structure-activity relationships of transition state analogues of human purine nucleoside phosphorylase.
abstract: The aza-C-nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of purine nucleoside phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2'-, 3'-, or 5'-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazapurine, as well as methylene-bridged analogues, have been synthesized and tested for their inhibition of human purine nucleoside phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.
authors.affiliation: Carbohydrate Chemistry, Industrial Research Limited, P. O. Box 31310, Lower Hutt, New Zealand.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Evans
authors.forename: Richard H
authors.initials: RH
authors.lastname: Furneaux
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lewandowicz
authors.forename: Vern L
authors.initials: VL
authors.lastname: Schramm
authors.forename: Peter C
authors.initials: PC
authors.lastname: Tyler
mesh_terms: D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D011684:Purine Nucleosides; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011684:Purine Nucleosides; D011744:Pyrimidinones; D011758:Pyrroles; C113100:immucillin G; C113101:forodesine; D011683:Purine-Nucleoside Phosphorylase