Haloanilino Derivatives of Pyrimidines, Purines, and Purine Nucleoside Analogs: Synthesis and Activity against Human Cytomegalovirus

1995 ◽  
Vol 38 (10) ◽  
pp. 1811-1819 ◽  
Author(s):  
Maria Medveczky ◽  
Te-Fang Yang ◽  
Joseph Gambino ◽  
Peter Medveczky ◽  
George E. Wright
Keyword(s):  
Human Cytomegalovirus ◽  
Nucleoside Analogs ◽  
Purine Nucleoside ◽  
Derivatives Of

scholarly journals Tri-Cyclic Nucleobase Analogs and their Ribosides as Substrates of Purine-Nucleoside Phosphorylases. II Guanine and Isoguanine Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1493 ◽  
Author(s):  
Stachelska-Wierzchowska ◽  
Wierzchowski ◽  
Górka ◽  
Bzowska ◽  
Wielgus-Kutrowska
Keyword(s):  
Nucleoside Analogs ◽  
Purine Nucleoside ◽  
Moderate Activity ◽  
Wild Type ◽  
E Coli ◽  
Single Compound ◽  
Neutral Aqueous Medium ◽  
Nucleoside Phosphorylases ◽  
Derivatives Of ◽  
Modest Activity

Etheno-derivatives of guanine, O6-methylguanine, and isoguanine were prepared and purified using standard methods. The title compounds were examined as potential substrates of purine-nucleoside phosphorylases from various sources in the reverse (synthetic) pathway. It was found that 1,N2-etheno-guanine and 1,N6-etheno-isoguanine are excellent substrates for purine-nucleoside phosphorylase (PNP) from E. coli, while O6-methyl-N2,3-etheno-guanine exhibited moderate activity vs. this enzyme. The latter two compounds displayed intense fluorescence in neutral aqueous medium, and so did the corresponding ribosylation products. By contrast, PNP from calf spleens exhibited only modest activity towards 1,N6-etheno-isoguanine; the remaining compounds were not ribosylated by this enzyme. The enzymatic ribosylation of 1,N6-etheno-isoguanine using two forms of calf PNP (wild type and N243D) and E. coli PNP (wild type and D204N) gave three different products, which were identified on the basis of NMR analysis and comparison with the product of the isoguanosine reaction with chloroacetic aldehyde, which gave an essentially single compound, identified unequivocally as N9-riboside. With the wild-type E. coli enzyme as a catalyst, N9--d- and N7--d-ribosides are obtained in proportion ~1:3, while calf PNP produced another riboside, tentatively identified as N6--d-riboside. The potential application of various forms of PNP for synthesis of the tri-cyclic nucleoside analogs is discussed.

Metabolism and action of purine nucleoside analogs

1991 ◽  
Vol 49 (3) ◽  
pp. 239-268 ◽  
Author(s):  
William Plunkett ◽  
Priscilla P. Saunders
Keyword(s):  
Nucleoside Analogs ◽  
Purine Nucleoside

scholarly journals Relationship between Autophosphorylation and Phosphorylation of Exogenous Substrates by the Human Cytomegalovirus UL97 Protein Kinase

2002 ◽  
Vol 76 (23) ◽  
pp. 11943-11952 ◽  
Author(s):  
Moon-Chang Baek ◽  
Paula M. Krosky ◽  
Donald M. Coen
Keyword(s):  
Protein Kinase ◽  
Fusion Protein ◽  
Human Cytomegalovirus ◽  
Time Course ◽  
Insect Cells ◽  
Nucleoside Analogs ◽  
Phosphatase Treatment ◽  
Exogenous Substrate ◽  
The Relationship ◽  
Exogenous Substrates

ABSTRACT Human cytomegalovirus encodes an unusual protein kinase, UL97, which is a member of the HvUL family of protein kinases encoded by diverse herpesviruses. UL97 is able to autophosphorylate and to phosphorylate certain exogenous substrates, including nucleoside analogs such as ganciclovir. It has previously been concluded that phosphorylation of UL97 is essential for its phosphorylation of ganciclovir. We examined the relationship between autophosphorylation of UL97 and its activity on exogenous substrates. Glutathione S-transferase-UL97 fusion protein purified from insect cells was found to be already partially phosphorylated, but neither extensive autophosphorylation nor phosphatase treatment meaningfully altered the time course of its phosphorylation of the exogenous substrate, histone H2B. Sequencing and mass spectrometric analyses of 32P-labeled tryptic peptides of the UL97 fusion protein identified nine sites of autophosphorylation, all within the first 200 residues of the protein, outside of conserved protein kinase subdomains. A peptide corresponding to the N-terminal UL97 segment that was most extensively autophosphorylated was readily phosphorylated by UL97, confirming that fusion protein sequences are not required for phosphorylation at this site. Deletion mutants lacking at least the first 239 residues exhibited drastically reduced autophosphorylation (<5%) but retained near-wild-type H2B phosphorylation activity. Baculoviruses expressing these mutants efficiently directed the phosphorylation of ganciclovir in insect cells. Taken together, these results identify the autophosphorylation sites of a herpesvirus protein kinase and show that autophosphorylation of UL97 is not required for phosphorylation of exogenous substrates.

scholarly journals Diverse models for anti-HIV activity of purine nucleoside analogs

2015 ◽  
Vol 9 (1) ◽  
Author(s):  
Naveen Khatri ◽  
Viney Lather ◽  
A K Madan
Keyword(s):  
Nucleoside Analogs ◽  
Purine Nucleoside ◽  
Anti Hiv
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