Fujita M, Otsuka M, Sugiura Y
Institute for Chemical Research, Kyoto University, Japan.
J Med Chem. 1996 Jan 19;39(2):503-7. doi: 10.1021/jm950831t.
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.
HIV-EP1是一种C2H2型锌指蛋白，它能与HIV前病毒长末端重复序列中存在的DNA κB位点结合。此前我们报道了具有组氨酸-吡啶-组氨酸骨架的锌螯合剂，并成功通过从锌指结构域去除锌来抑制HIV-EP1的DNA结合。为了增强我们之前锌螯合剂的抑制活性，本文合成了包含吡啶和氨基链烷硫醇的新型螯合剂。这些螯合剂对HIV-EP1的DNA结合表现出显著的抑制活性。特别是，其中一种具有双(2-巯基乙基)氨基侧链的螯合剂显示出的抑制活性（IC50，约4 microM）比我们之前报道的最强抑制剂强10倍。这些螯合剂似乎通过一种不同于之前基于组氨酸的抑制剂的机制来抑制HIV-EP1的DNA结合。
