C - Chemistry – Metallurgy – 12 – Q
Patent
C - Chemistry, Metallurgy
12
Q
C12Q 1/68 (2006.01) G01N 33/50 (2006.01)
Patent
CA 2312362
The present invention relates to an in vitro mammalian DNA replication system and to a method for identifying agonists and antagonists of DNA replication. The method comprises contacting in vitro a plasmid with a mixture comprising nuclear or cytoplasmic extracts from HeLa cells, the drug and a mixture of nucleotides, assessing the stimulation or the inhibition of initiation of DNA replication and the elongation of nascent DNA produced by the drug, and identifying the essential structures of the drug by quantitative structure- activity relationship (QSAR) analysis deriving relationships between the structural features of the drug and biological responses produced by the binding of the drug to the target receptor. The plasmid has a target receptor and comprises a specific mammalian origin of DNA replication.
L'invention concerne un système de réplication in vitro d'ADN mammifère et un procédé servant à identifier des agonistes et des antagonistes de réplication d'ADN. Ce procédé consiste à mettre en contact in vitro un plasmide avec un mélange contenant des extraits nucléaires et cytoplasmiques de cellules de HeLa, le médicament et un mélange de nucléotides, à évaluer la stimulation ou l'inhibition du déclenchement de la réplication de l'ADN et l'élongation de l'ADN naissant produite par le médicament et à identifier les structures essentielles du médicament au moyen d'une analyse quantitative des rapports entre structure et activité (QSAR) permettant de calculer des rapports entre les caractéristiques de la structure du médicament et les réponses biologiques produites par la fixation du médicament au récepteur ciblé. Le plasmide possède un récepteur ciblé et contient une réplication d'ADN d'origine spécifiquement mammifère.
Azzaoui Kamal
Diaz-Perez Maria
Price Gerald B.
Wainer Irving W.
Zannis-Hadjopoulos Maria
Ogilvy Renault
University Mcgill
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