Synthesis of taurospongin A: a potent inhibitor of DNA polymerase and HIV reverse transcriptase, using π-allyltricarbonyliron lactone complexes

2002 ◽  
pp. 1624-1625 ◽  
Author(s):  
Christopher J. Hollowood ◽  
Steven V. Ley ◽  
Shigeo Yamanoi
Keyword(s):  
Reverse Transcriptase ◽  
Dna Polymerase ◽  
Potent Inhibitor ◽  
Hiv Reverse Transcriptase

scholarly journals Kinetic Interaction of the Diphosphates of 9-(2-phosphonylmethoxyethyl)adenine and Other anti-HIV Active Purine Congeners with HIV Reverse Transcriptase and Human DNA Polymerases α, β and γ

1995 ◽  
Vol 6 (4) ◽  
pp. 217-221 ◽  
Author(s):  
J. M. Cherrington ◽  
S. J. W. Allen ◽  
N. Bischofberger ◽  
M. S. Chen
Keyword(s):  
Reverse Transcriptase ◽  
Dna Polymerase ◽  
Dna Polymerases ◽  
Inhibitory Effects ◽  
Hiv Reverse Transcriptase ◽  
Dna Polymerase Β ◽  
Human Dna ◽  
Dna Template ◽  
Anti Hiv ◽  
Micromolar Range

The inhibitory effects of the diphosphates of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and its analogues on HIV reverse transcriptase and human DNA polymerases α, β, and γ have been studied. The analogues investigated are the diphosphates of 9-(2-phosphonylmethoxypropyl)adenine (PMPApp), 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine (PMPDAPpp), and (2R,5R)-9-[2,5-dihydro-5-(phosphonyl methoxy)-2-furanyl]adenine (D4APpp). These four compounds are much more inhibitory to HIV reverse transcriptase when an RNA template rather than a DNA template is used. The Ki, values for the four compounds range from 11 to 22 nM with an RNA template. The Ki, values for ddCTP and AZTTP are 54 nM and 8 nM, respectively. PMEApp and its analogues show varying degrees of inhibition of the human DNA polymerases. The Ki, values for PMEApp, PMPApp and PMPDAPpp against DNA polymerase α are in the micromolar range, while D4APpp is a poor inhibitor of this enzyme with a Ki, value of 65.9 μM. The inhibition of DNA polymerase β by PMEApp, PMPApp and D4APpp is minimal, while PMPDAPpp shows higher inhibition of DNA polymerase β with a Ki, value of 9.71 μM. The Ki, values for PMEApp and D4APpp against DNA polymerase γ are submicromolar, while PMPApp and PMPDAPpp are much less inhibitory to this enzyme. For comparison, ddCTP was found to be a more potent inhibitor of DNA polymerases β and γ than the diphosphates of PMEA and its analogues.

Functional characterization of RNA-dependent DNA polymerase and RNase H activities of a recombinant HIV reverse transcriptase

Biochemistry ◽  
1991 ◽  
Vol 30 (10) ◽  
pp. 2651-2655 ◽  
Author(s):  
Cheng Keat Tan ◽  
Jian Zhang ◽  
Zhao Yan Li ◽  
W. Gary Tarpley ◽  
Kathleen M. Downey ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Dna Polymerase ◽  
Functional Characterization ◽  
Rnase H ◽  
Hiv Reverse Transcriptase

The Effect of Absolute Configuration on the Anti-HIV and Anti-HBV Activity of Nucleoside Analogues

1995 ◽  
Vol 6 (6) ◽  
pp. 345-355 ◽  
Author(s):  
P. A. Furman ◽  
J. E. Wilson ◽  
J. E. Reardon ◽  
G. R. Painter
Keyword(s):  
Dna Polymerase ◽  
Potent Inhibitor ◽  
Hbv Dna ◽  
The Other ◽  
Nucleoside Analogues ◽  
Differential Inhibition ◽  
Hiv Reverse Transcriptase ◽  
Hiv Rt ◽  
Anti Hiv ◽  
Selective Activity

This review concerns the effect of stereoisomerism on the selective activity of anti-HIV and anti-HBV nucleoside analogues. The synthesis of a number of nucleoside analogues with anti-HIV and anti-HBV activity yields mixtures of 1-β-D and 1-β-L stereoisomers. Anti-HIV and anti-HBV activity is associated primarily with one of the two enantiomers and the more potent activity does not always reside with the 1-β-D configuration characteristic of natural nucleosides. In the case of HIV, the origin of this stereoselectivity appears to be the result of differential metabolism of the analogues and not due to differential inhibition of the target enzyme; the HIV reverse transcriptase. However, mutations at position 184 of the HIV-RT does result in stereoselective inhibition of the enzyme. On the other hand, with HBV, there is also a stereoselective inhibition of the HBV DNA polymerase, where the 5′-triphosphate of the 1-β-L enantiomer is the more potent inhibitor.

Sign in / Sign up

Export Citation Format

Share Document