METHOD FOR IDENTIFYING AGONISTS AND ANTAGONISTS OF DNA REPLICATION USING AN IN VITRO MAMMALIAN DNA REPLICATION SYSTEM

摘要

The present invention relates to an in vitro mammalian DNA replication systemand to a method for identifying agonists and antagonists of DNA replication.The method comprises contacting in vitro a plasmid with a mixture comprisingnuclear or cytoplasmic extracts from HeLa cells, the drug and a mixture ofnucleotides, assessing the stimulation or the inhibition of initiation of DNAreplication and the elongation of nascent DNA produced by the drug, andidentifying the essential structures of the drug by quantitative structure-activity relationship (QSAR) analysis deriving relationships between thestructural features of the drug and biological responses produced by thebinding of the drug to the target receptor. The plasmid has a target receptorand comprises a specific mammalian origin of DNA replication.