Document 0703
 DOCN  M9590703
 TI    High-throughput screening for hiv-1 integrase inhibitors: one YEAR
       AFTER.
 DT    9509
 AU    Mayaux JF; Huet T; Pernelle C; Becquart J; Gueguen JC; Tahraoui L; Evers
       M; Henin Y; Bousseau A; Dereu N; Rhone-Poulenc Rorer, Vitry-Alfortville
       Research Center, Vitry Sur; Seine Cedex, France.
 SO    NIH Conf Retroviral Integrase. 1995 Jan 19-20;:(Session III, speakers'
       abstracts - unpaged). Unique Identifier : AIDSLINE AIDS/95920016
 AB    Although HIV-1 integrase obviously represents a very attractive
       pharmacological target for the treatment of HIV infection, specific and
       potent integrase inhibitors have not yet been described. In order to
       find such molecules, recombinant HIV-1 integrase was first purified from
       E. coli and fully characterized. A high throughput screening assay using
       the Scintillation Proximity Assay (SPA) technology (Amersham) was then
       set up to search for potential integrase inhibitors from various sources
       (chemical libraries, natural compounds, peptide libraries). The strategy
       to identify valuable leads for chemical optimization will be discussed.
       Compounds exhibiting activity in the primary assay can be evaluated for
       specificity in DNA endonuclease/ mobility assays, as well as in SPA
       assays involving other HIV-1 enzymes/ proteins interacting with nucleic
       acids (reverse transcriptase, nucleocapsid protein NCp7). Selected
       compounds are then studied in the three classical integrase biochemical
       assays monitoring either dinucleotide cleavage, strand transfer or
       disintegration. Since it is highly desirable to identify compounds able
       to block HIV-1 replication in cellular acute infection assays and to
       demonstrate that this cellular activity is indeed due to a specific
       blockage of the integration step, we have devised PCR assays able to
       distinguish such an activity in cells. Interesting candidate compounds
       are currently being investigated through this process.
 DE    Binding Sites  Capsid/METABOLISM  DNA
       Nucleotidyltransferases/*ANTAGONISTS & INHIB/METABOLISM  DNA Restriction
       Enzymes/METABOLISM  Enzyme Inhibitors  HIV-1/*ENZYMOLOGY/PHYSIOLOGY
       Recombinant Proteins  Reverse Transcriptase/METABOLISM  Scintillation
       Counting  Virus Replication  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).