       Document 0077
 DOCN  M9630077
 TI    Identification of a hexapeptide inhibitor of the human immunodeficiency
       virus integrase protein by using a combinatorial chemical library.
 DT    9603
 AU    Puras Lutzke RA; Eppens NA; Weber PA; Houghten RA; Plasterk RH; Division
       of Molecular Biology, The Netherlands Cancer Institute,; Amsterdam, The
       Netherlands.
 SO    Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11456-60. Unique Identifier
       : AIDSLINE MED/96102132
 AB    Integration of human immunodeficiency virus (HIV) DNA into the human
       genome requires the virus-encoded integrase (IN) protein, and therefore
       the IN protein is a suitable target for antiviral strategies. To find a
       potent HIV IN inhibitor, we screened a synthetic peptide combinatorial
       library. We identified a hexapeptide with the sequence HCKFWW that
       inhibits IN-mediated 3'-processing and integration with an IC50 of 2
       microM. The peptide is active on IN proteins from other retroviruses
       such as HIV-2, feline immunodeficiency virus, and Moloney murine
       leukemia virus, supporting the notion that a conserved region of IN is
       targeted. The hexapeptide was also tested in the disintegration
       reaction. This phosphoryl-transfer reaction can be carried out by the
       catalytic core of IN alone, and the peptide HCKFWW was found to inhibit
       this reaction, suggesting that the hexapeptide acts at or near the
       catalytic site of IN. Identification of an IN hexapeptide inhibitor
       provides proof of concept for the approach, and, moreover, this peptide
       may be useful for structure-function analysis of IN.
 DE    Amino Acid Sequence  Comparative Study  Drug Screening  DNA
       Nucleotidyltransferases/*ANTAGONISTS & INHIB  Enzyme
       Inhibitors/*PHARMACOLOGY  HIV-1/*ENZYMOLOGY/GENETICS  HIV-2/DRUG
       EFFECTS/ENZYMOLOGY/GENETICS  Immunodeficiency Virus, Feline/DRUG
       EFFECTS/GENETICS  Molecular Sequence Data  Moloney Leukemia Virus/DRUG
       EFFECTS/ENZYMOLOGY/GENETICS  Oligopeptides/CHEMICAL
       SYNTHESIS/*PHARMACOLOGY  Retroviridae/DRUG EFFECTS/ENZYMOLOGY/GENETICS
       Structure-Activity Relationship  Support, Non-U.S. Gov't  Virus
       Integration/*DRUG EFFECTS  JOURNAL ARTICLE

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

