Chemical modifications of aminonaphthalenesulfonic acid derivatives increase effectivity and specificity of reverse transcriptase inhibition and change mode of action of reverse transcriptase and DNA polymerase alpha inhibition.
The reverse transcriptase (RT) inhibition and the specificity of 15 aminonaphthalenesulfonic acid derivatives were examined with RT of a simian immunodeficiency virus derived from an African green monkey (SIVagmTYO-7). The two compounds with the strongest RT inhibition (NF415) or the highest specificity (NF345), together with suramin, were evaluated against polymerase alpha-primase complex from calf thymus. We have also compared the kinetics of inhibition of the viral and the cellular polymerase by these three compounds. While RT inhibition followed a mixed competitive and non-competitive mechanism, inhibition of the DNA polymerase alpha was competitive for suramin and non-competitive for NF415 and NF345. Certain structural characteristics appeared to be common for specific RT inhibitors.
Oesterle
R
R
German Primate Centre, Department of Virology and Immunology, Göttingen.
Jurkiewicz
E
E
Lüke
W
W
Nickel
P
P
Hunsmann
G
G
Jentsch
K D
KD
D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004257:DNA Polymerase II / Q000187:drug effects* / Q000302:isolation & purification; D019915:DNA Primase; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D009282:Naphthalenesulfonates / Q000494:pharmacology* / Q000633:toxicity; D010539:Permeability; D012316:RNA Nucleotidyltransferases / Q000187:drug effects* / Q000302:isolation & purification; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects* / Q000302:isolation & purification; D018894:Reverse Transcriptase Inhibitors; D015302:Simian Immunodeficiency Virus / Q000201:enzymology* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013498:Suramin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity
D009282:Naphthalenesulfonates; D018894:Reverse Transcriptase Inhibitors; D013498:Suramin; D019915:DNA Primase; D012316:RNA Nucleotidyltransferases; D012194:RNA-Directed DNA Polymerase; D004257:DNA Polymerase II