Disease relevance of AIDS086341

• The acyclic nucleoside phosphonate analog 9-(2-phosphonylmethoxyethyl)adenine (PMEA) was recently found to be effective as an inhibitor of visna virus replication and cytopathic effect in sheep choroid plexus cultures [1].
• The acyclic phosphonate analog adefovir is a potent inhibitor of retroviruses, including human immunodeficiency virus (HIV) type 1, and, unlike some antiviral nucleosides, does not require the initial phosphorylation step for its activity [2].
• Cidofovir [CDV,(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC] is an acyclic cytosine nucleoside phosphonate analog with potent in vitro and in vivo activity against a broad spectrum of herpesviruses [3].
• The minor effect of DBP on HSA may indicate that the toxicity of the phosphonate analog is much lower than toxicities of DDP isomers, most likely due to kinetic reasons [4].
• Adefovir dipivoxil, a prototype phosphonate analog, has been approved for chronic hepatitis B virus therapy, and additional phosphonate analogs and di- and tri-nucleotides are under development [5].

High impact information on AIDS086341

• (i) When hydrolysis of C6-NBD-PA to diacylglycerol was prevented by using a nonhydrolyzable fluorescent phosphonate analog, intense labeling of the plasma membrane occurred but fluorescent lipid did not enter the cytoplasm of cells [6].
• A phosphonate analog of N-acetyl neuraminic acid (PANA) has been designed as a potential neuraminidase (NA) inhibitor and synthesized as both the alpha (ePANA) and beta (aPANA) anomers [7].
• The IC50 for inhibition of adenylyl cyclase by the MOPA phosphonate analog was similar to that of MOPA, the maximal inhibitions were comparable (approximately 45% inhibition of hormone-stimulated adenylyl cyclase), and the effects of both appeared to be mediated by Gi, because treatment with islet-activating protein reduced the inhibition to 5-10% [8].
• (S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) is a nucleoside phosphonate analog which in its active diphosphorylated form is known to inhibit herpesvirus DNA polymerase [9].
• The simulations were compared to unrestrained simulations of the EPSP synthase tetrahedral intermediate and its phosphonate analog [10].

Biological context of AIDS086341

• Retro-Diels-Alder reaction: possible involvement in the metabolic activation of 7-oxabicyclo[2.2.1]hepta-2(3),5(6)-diene-2,3-dicarboxylates and a phosphonate analog [11].
• We have demonstrated previously that D-myo-inositol 4-(hexadecyloxy)-3(S)-methoxybutanephosphonate (C4-PI), an isosteric phosphonate analog of phosphatidylinositol developed to inhibit inositol lipid metabolism, was unable to inhibit phosphatidylinositol (PI) 3-kinase activity [12].
• The structures of 2-lactyl-ThDP (LThDP, 2) and its stable phosphonate analog, of 2-hydroxyethyl-ThDP (HEThDP, 3) enamine and of 2-acetyl-ThDP (AcThDP, 4; all shown bound to the enzyme's active site) provide profound insights into the chemical mechanisms and the stereochemical course of thiamin catalysis [13].

Anatomical context of AIDS086341

• Mechanism of uptake of the phosphonate analog (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) in Vero cells [14].

Gene context of AIDS086341

• Its phosphonate analog 17, however, was neither a significant antibacterial agent nor a good beta-lactamase inhibitor [15].

Analytical, diagnostic and therapeutic context of AIDS086341

• 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), an acyclic nucleoside phosphonate analog, is active against several retroviruses and herpesviruses and has shown anti-human immunodeficiency virus (HIV) activity in clinical trials [16].

References