Pyrophosphate analogues as inhibitors of DNA polymerases of cytomegalovirus, herpes simplex virus and cellular origin.
Biochim Biophys Acta
; 696(2): 115-23, 1982 Feb 26.
Article
em En
| MEDLINE
| ID: mdl-6277381
ABSTRACT
Several pyrophosphate analogues have been compared for their ability to inhibit the activities of isolated cytomegalovirus (CMV) DNA polymerase, herpes simplex virus type 1 (HSV 1) DNA polymerase and calf thymus DNA polymerase alpha. The most effective inhibitors were phosphonoformate and phosphonoacetate. Although not identical, the structural requirements for compounds inhibitory to CMV and HSV-1 DNA polymerase were specific, with two negatively charged groups in close vicinity. The CMV DNA polymerase was more susceptible to certain phosphonoacetates containing bulky hydrophobic alpha-substituents than was the HSV-1 DNA polymerase. No example of the converse preference was found. The inhibition of CMV DNA polymerase by phosphonoformate, hypophosphate, alpha-hydroxyphosphonoacetate and alpha-nonylphosphonoacetate was linear non-competitive with the deoxyribonucleoside triphosphates as variable substrates. Phosphonoformate, phosphonoacetate, and to a lesser extent alpha-hydroxyphosphonoacetate, carbonyldiphosphonate and alpha-nonylphosphonoacetate also inhibited the focus formation by CMV in cell-culture.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organofosforados
/
Timo
/
Simplexvirus
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Inibidores da Síntese de Ácido Nucleico
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Citomegalovirus
Limite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
1982
Tipo de documento:
Article