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National Repository of Grey Literature

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Acyclic nucleoside bis-phosphonates as potent inhibitors of 6-oxopurine phosphoribosyltransferases Špaček, Petr ; Keough, D. T. ; Vrbková, Silvie ; Slavětínská, Lenka ; Janeba, Zlatko ; Naesens, L. ; Edstein, M. D. ; Chavchich, M. ; Wang, T. H. ; de Jersey, J. ; Guddat, L. W. ; Hocková, Dana Hypoxanthine-guanin-(xanthine) phosphoribosyltransferase (HG(X)PRT) is critical for the survival of malarial parasites Plasmodium falciparum and Plasmodium vivax. These parasites rely on HG(X)PRT to make 6-oxopurine nucleoside monophosphates. Specific acyclic nucleoside phosphonates (ANPs) inhibit HG(X)PRT and thus have an anti-plasmodial activity. Crystal structures of human HGPRT in complex with several ANP-based inhibitors suggested that attachment of the second phosphonate group which could occupy the pyrophosphate binding site may lead to increased affinity of these compounds. Detailed record

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