Document 0416
 DOCN  M9650416
 TI    Metal-chelating inhibitors of a zinc finger protein HIV-EP1. Remarkable
       potentiation of inhibitory activity by introduction of SH groups.
 DT    9605
 AU    Fujita M; Otsuka M; Sugiura Y; Institute for Chemical Research, Kyoto
       University, Japan.
 SO    J Med Chem. 1996 Jan 19;39(2):503-7. Unique Identifier : AIDSLINE
       MED/96145184
 AB    HIV-EP1 is a C2H2 type zinc finger protein which binds to DNA kappa B
       site present in the long terminal repeat of HIV provirus. Previously we
       have reported zinc chelators having histidine--pyridine--histidine
       skeleton and were successful in inhibiting the DNA binding of HIV-EP1 by
       removing zinc from the zinc finger domain. Aiming at the potentiation of
       the inhibitory activity of our previous zinc chelators, herein
       synthesized were novel chelators comprising pyridine and
       aminoalkanethiol. These showed marked inhibitory activity on the DNA
       binding of HIV-EP1. In particular, one of them having a
       bis(2-mercaptoethyl) amino side chain showed inhibitory activity (IC50,
       approximately 4 microM) 10 times stronger than that of the strongest
       inhibitor that we reported previously. It appeared that these inhibited
       the DNA binding of HIV-EP1 by a mechanism distinct from that of the
       previous histidine-based inhibitors.
 DE    Animal  Base Sequence  Chelating Agents/CHEMISTRY/*PHARMACOLOGY
       DNA/METABOLISM  DNA-Binding Proteins/*ANTAGONISTS & INHIB/METABOLISM
       Mice  Molecular Sequence Data  NF-kappa B/METABOLISM  Sulfhydryl
       Compounds/*CHEMISTRY  Support, Non-U.S. Gov't  Zinc/*CHEMISTRY  *Zinc
       Fingers  JOURNAL ARTICLE

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