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Metal-Chelating Inhibitors of a Zinc Finger Protein HIV-EP1. Remarkable Potentiation of Inhibitory Activity by Introduction of SH Groups

1996; American Chemical Society; Volume: 39; Issue: 2 Linguagem: Inglês

10.1021/jm950831t

1520-4804

Mikako Fujita, Masami Otsuka, Yukio Sugiura,

Ferrocene Chemistry and Applications

HIV-EP1 is a C2H2 type zinc finger protein which binds to DNA κB 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, ∼4 μM) 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.