3t6y

5'-Diphenyl Nucleoside Inhibitors of Plasmodium falciparum dUTPase

spinqualitylabelsall models 3t6y, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3t6y is a 4 chain structure with sequence from Plasmodium falciparum 3D7 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: DU2, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8II92_PLAF7 Publication Abstract from PubMed Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for malaria. We previously reported some 5'-tritylated deoxyuridine analogues (both cyclic and acyclic) as selective inhibitors of the Plasmodium falciparum dUTPase. Modelling studies indicated that it might be possible to replace the trityl group with a diphenyl moiety, as two of the phenyl groups are buried, whereas the third is exposed to solvent. Herein we report the synthesis and evaluation of some diphenyl analogues that have lower lipophilicity and molecular weight than the trityl lead compound. Co-crystal structures show that the diphenyl inhibitors bind in a similar manner to the corresponding trityl derivatives, with the two phenyl moieties occupying the predicted buried phenyl binding sites. The diphenyl compounds prepared show similar or slightly lower inhibition of PfdUTPase, and similar or weaker inhibition of parasite growth than the trityl compounds. Design, synthesis, and evaluation of 5'-diphenyl nucleoside analogues as inhibitors of the Plasmodium falciparum dUTPase.,Hampton SE, Baragana B, Schipani A, Bosch-Navarrete C, Musso-Buendia JA, Recio E, Kaiser M, Whittingham JL, Roberts SM, Shevtsov M, Brannigan JA, Kahnberg P, Brun R, Wilson KS, Gonzalez-Pacanowska D, Johansson NG, Gilbert IH ChemMedChem. 2011 Oct 4;6(10):1816-31. PMID:22049550 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DUTPase 3D structures

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