title: Discovery and analysis of inhibitors of the human immunodeficiency integrase.
abstract: An essential step in the replication of retroviruses is the integration of a DNA copy of the viral genome into the genome of the host cell. Integration encompasses a series of ordered endonucleolytic and DNA strand transfer reactions catalyzed by the viral enzyme, integrase. The requirement for integrase activity in the propagation of HIV-1 in cell culture defines the enzyme as a potential target for chemotherapeutic intervention. We have therefore developed a non-radioisotopic microtiter plate assay which can be used to identify novel inhibitors of integrase from random chemical screens and for the bioassay driven isolation of inhibitors from natural products. This assay uncouples various steps in the reaction pathway and therefore can be exploited to characterize inhibitors. In this monograph we describe a series of modifications to the method which facilitate such mechanistic studies using as an example a series of previously described integrase inhibitors.
authors.affiliation: Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19446, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hazuda
authors.forename: P J
authors.initials: PJ
authors.lastname: Felock
authors.forename: J C
authors.initials: JC
authors.lastname: Hastings
authors.forename: B
authors.initials: B
authors.lastname: Pramanik
authors.forename: A L
authors.initials: AL
authors.lastname: Wolfe
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D002474:Cell-Free System; D004279:DNA, Viral / Q000378:metabolism; D004341:Drug Evaluation; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008722:Methods; D019065:Virus Assembly / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D002413:Cations, Divalent; D004279:DNA, Viral; D019428:HIV Integrase Inhibitors