title: Acyclic ribooxacarbenium ion mimics as transition state analogues of human and malarial purine nucleoside phosphorylases.
abstract: Transition state analogues of PNP, the Immucillins and DADMe-Immucillins, were designed to match transition state features of bovine and human PNPs, respectively. A third generation of inhibitors has been designed that contain an acyclic iminoalcohol to replace the cyclic mimic of the ribooxacarbenium ion at the transition states of PNPs. The best third generation inhibitor is equivalent to the best inhibitors found in the previous transition state analogues.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Erika A
authors.initials: EA
authors.lastname: Taylor
authors.forename: Keith
authors.initials: K
authors.lastname: Clinch
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kelly
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Gary B
authors.initials: GB
authors.lastname: Evans
authors.forename: Peter C
authors.initials: PC
authors.lastname: Tyler
authors.forename: Vern L
authors.initials: VL
authors.lastname: Schramm
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007097:Imines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D010963:Plasmodium falciparum / Q000201:enzymology*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D011744:Pyrimidinones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011759:Pyrrolidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: C508755:DADMe-immucillin H; D007097:Imines; D011744:Pyrimidinones; D011759:Pyrrolidines; D011683:Purine-Nucleoside Phosphorylase