title: 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.
abstract: 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.
authors.affiliation: German Primate Centre, Department of Virology and Immunology, Göttingen.
authors.forename: R
authors.initials: R
authors.lastname: Oesterle
authors.forename: E
authors.initials: E
authors.lastname: Jurkiewicz
authors.forename: W
authors.initials: W
authors.lastname: Lüke
authors.forename: P
authors.initials: P
authors.lastname: Nickel
authors.forename: G
authors.initials: G
authors.lastname: Hunsmann
authors.forename: K D
authors.initials: KD
authors.lastname: Jentsch
mesh_terms: 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
chemical_list: D009282:Naphthalenesulfonates; D018894:Reverse Transcriptase Inhibitors; D013498:Suramin; D019915:DNA Primase; D012316:RNA Nucleotidyltransferases; D012194:RNA-Directed DNA Polymerase; D004257:DNA Polymerase II