Debyser Z, Pauwels R, Baba M, Desmyter J, De Clercq E
Rega Institute for Medical Research, Catholic University of Leuven, Belgium.
Mol Pharmacol. 1992 May;41(5):963-8.
Recently, several classes of compounds have been shown to be potent, selective, and specific inhibitors of human immunodeficiency virus type 1 replication in vitro. These include the tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione (TIBO) and the 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives. Both the TIBO and HEPT derivatives specifically inhibit human immunodeficiency virus type 1 reverse transcriptase (RT). From a comparative study of the characteristics of RT inhibition by TIBO and HEPT, and from the competition between TIBO and HEPT for RT inhibition, we infer that both classes of compounds, although structurally unrelated, are targeted at the same site of the enzyme. Detailed functional and kinetic analyses indicate that this target site is functionally and possibly also spatially related to the substrate binding site.
最近，几类化合物已被证明在体外对1型人类免疫缺陷病毒复制具有强效、选择性和特异性抑制作用。这些化合物包括四氢咪唑并[4,5,1-jk][1,4]-苯并二氮杂卓-2(1H)-酮和-硫酮（TIBO）以及1-[(2-羟乙氧基)甲基]-6-(苯硫基)胸腺嘧啶（HEPT）衍生物。TIBO和HEPT衍生物均特异性抑制1型人类免疫缺陷病毒逆转录酶（RT）。通过对TIBO和HEPT抑制RT特性的比较研究，以及TIBO和HEPT之间对RT抑制的竞争，我们推断这两类化合物虽然结构不相关，但都作用于该酶的同一部位。详细的功能和动力学分析表明，这个靶位点在功能上并且可能在空间上也与底物结合位点相关。
