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Stereo-Defined Acyclic Nucleoside Phosphonates are Selective and Potent Inhibitors of Parasite 6-Oxopurine Phosphoribosyltransferases.

Klejch T, Keough DT, King G, Doleželová E, Česnek M, Buděšínský M, Zíková A, Janeba Z, Guddat LW, Hocková D
J Med Chem 65 4030-4057 (2022)
Related entries: 7san, 7scr

Cited: 1 times
EuropePMC logo PMID: 35175749

Abstract

Pathogens such as Plasmodium and Trypanosoma spp. are unable to synthesize purine nucleobases. They rely on the salvage of these purines and their nucleosides from the host cell to synthesize the purine nucleotides required for DNA/RNA production. The key enzymes in this pathway are purine phosphoribosyltransferases (PRTs). Here, we synthesized 16 novel acyclic nucleoside phosphonates, 12 with a chiral center at C-2', and eight bearing a second chiral center at C-6'. Of these, bisphosphonate (S,S)-

Articles citing this publication (1)

  1. Kinetic and Structural Characterization of Trypanosoma cruzi Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferases and Repurposing of Transition-State Analogue Inhibitors. Glockzin K, Meneely KM, Hughes R, Maatouk SW, Piña GE, Suthagar K, Clinch K, Buckler JN, Lamb AL, Tyler PC, Meek TD, Katzfuss A. Biochemistry 62 2182-2201 (2023)


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