Acyclic ribooxacarbenium ion mimics as transition state analogues of human and malarial purine nucleoside phosphorylases.
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.
Taylor
Erika A
EA
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Clinch
Keith
K
Kelly
Peter M
PM
Li
Lei
L
Evans
Gary B
GB
Tyler
Peter C
PC
Schramm
Vern L
VL
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
C508755:DADMe-immucillin H; D007097:Imines; D011744:Pyrimidinones; D011759:Pyrrolidines; D011683:Purine-Nucleoside Phosphorylase