Inhibition of herpes simplex virus DNA polymerase by diphosphates of acyclic phosphonylmethoxyalkyl nucleotide analogues
Jazyk angličtina Země Nizozemsko Médium print
Typ dokumentu srovnávací studie, časopisecké články
PubMed
2168689
DOI
10.1016/0166-3542(90)90066-g
PII: 0166-3542(90)90066-G
Knihovny.cz E-zdroje
- MeSH
- acyklovir analogy a deriváty chemická syntéza farmakologie MeSH
- adenin analogy a deriváty chemická syntéza farmakologie MeSH
- antivirové látky chemická syntéza farmakologie MeSH
- arabinofuranosylcytosintrifosfát farmakologie MeSH
- dideoxynukleotidy MeSH
- DNA-polymerasa I antagonisté a inhibitory MeSH
- DNA-polymerasa II antagonisté a inhibitory MeSH
- HeLa buňky MeSH
- inhibitory syntézy nukleových kyselin * MeSH
- kinetika MeSH
- lidé MeSH
- organofosfonáty * MeSH
- organofosforové sloučeniny chemická syntéza farmakologie MeSH
- replikace DNA účinky léků MeSH
- Simplexvirus účinky léků enzymologie MeSH
- thiminnukleotidy farmakologie MeSH
- zidovudin analogy a deriváty farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- 2',3'-dideoxythymidine triphosphate MeSH Prohlížeč
- 9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine MeSH Prohlížeč
- acyclovir triphosphate MeSH Prohlížeč
- acyklovir MeSH
- adefovir MeSH Prohlížeč
- adenin MeSH
- antivirové látky MeSH
- arabinofuranosylcytosintrifosfát MeSH
- dideoxynukleotidy MeSH
- DNA-polymerasa I MeSH
- DNA-polymerasa II MeSH
- inhibitory syntézy nukleových kyselin * MeSH
- organofosfonáty * MeSH
- organofosforové sloučeniny MeSH
- thiminnukleotidy MeSH
- zidovudin MeSH
- zidovudine triphosphate MeSH Prohlížeč
The inhibition of HSV-1 DNA polymerase and HeLa DNA polymerases alpha and beta by diphosphoryl derivatives of acyclic phosphonylmethoxyalkyl nucleotide analogues was studied and compared with the inhibition by ACV-TP, araCTP, ddTTP and AZT-TP. In the series of phosphonylmethoxyethyl (PME-) derivatives of heterocyclic bases, the inhibitory effect of their diphosphates on HSV-1 DNA polymerase decreased in the order 2-amino-PMEApp (Ki = 0.03 microM) much greater than PMEGpp greater than PMEApp greater than PMETpp much greater than PMECpp much greater than n8z7PMEApp greater than PMEUpp. The diphosphate derivative of the antiherpes agent (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl) adenine (HPMPA) proved to be a relatively weak inhibitor of HSV-1 DNA polymerase (Ki = 1.4 microM). The inhibitors could be divided into three groups: (a) the diphosphoryl derivatives of acyclic nucleotide analogues (PME-type and HPMPA) and ACV-TP specifically inhibit HSV-1 DNA polymerase and DNA polymerase alpha and do not significantly inhibit DNA polymerase beta; (b) AZT-TP and ddTTP are effective only against DNA polymerase beta, and (c) araCTP inhibits all three enzymes. When dATP was omitted from the reaction mixture, the addition of HPMPApp stimulated DNA synthesis by HSV-1 DNA polymerase indicating that HPMPApp is an alternative substrate for in vitro DNA synthesis catalyzed by this enzyme.
Citace poskytuje Crossref.org