Schneider J, Kent S B
Division of Biology, California Institute of Technology, Pasadena 91125.
Cell. 1988 Jul 29;54(3):363-8. doi: 10.1016/0092-8674(88)90199-7.
A protein corresponding to the putative protease of the human immunodeficiency virus 1 (HIV-1) has been prepared by total chemical synthesis. This 99 residue synthetic enzyme showed specific proteolytic activity on fragments of the natural gag precursor and on synthetic peptide substrates, two of which released fragments corresponding to the N terminus and C terminus of the protease molecule itself. The observed substrate specificity was not restricted to cleavage at Phe/Tyr-Pro bonds. Inhibition studies provided direct evidence that the HIV-1 protease belongs to the family of aspartic proteases. The availability of the HIV-1 protease as a defined molecular species has important implications for the design of specific inhibitors that do not interfere with the host cell metabolism as a possible route to antiviral agents against acquired immunodeficiency syndrome (AIDS).
一种与人类免疫缺陷病毒1型（HIV-1）假定蛋白酶相对应的蛋白质已通过全化学合成制备出来。这种由99个氨基酸残基组成的合成酶对天然gag前体片段和合成肽底物表现出特异性蛋白水解活性，其中两种底物释放出的片段分别对应于蛋白酶分子本身的N端和C端。观察到的底物特异性并不局限于在苯丙氨酸/酪氨酸-脯氨酸键处切割。抑制研究提供了直接证据，表明HIV-1蛋白酶属于天冬氨酸蛋白酶家族。HIV-1蛋白酶作为一种明确的分子物种的可得性，对于设计不干扰宿主细胞代谢的特异性抑制剂具有重要意义，这可能是开发抗获得性免疫缺陷综合征（艾滋病）抗病毒药物的一条途径。
