8-Aza-immucillins as transition-state analogue inhibitors of purine nucleoside phosphorylase and nucleoside hydrolases.
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.
Evans
Gary B
GB
Carbohydrate Chemistry, Industrial Research Limited, P.O. Box 31-310, Lower Hutt, New Zealand. g.evans@irl.cri.nz
Furneaux
Richard H
RH
Gainsford
Graeme J
GJ
Hanson
John C
JC
Kicska
Gregory A
GA
Sauve
Antony A
AA
Schramm
Vern L
VL
Tyler
Peter C
PC
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
D001372:Aza Compounds; D004791:Enzyme Inhibitors; D011684:Purine Nucleosides; D007288:Inosine; D011683:Purine-Nucleoside Phosphorylase; D009699:N-Glycosyl Hydrolases; D000241:Adenosine