Peptide substrates and inhibitors of the HIV-1 protease.
Peptide substrates and inhibitors of the HIV-1 protease.
复制标题
HIV-1 蛋白酶的肽底物和抑制剂。
DOI：
10.1016/0006-291x(89)90008-9
复制
发表时间：
1989
影响因子：
3.1
通讯作者：
Metcalf,BW
中科院分区：
文献类型：
--
作者：
Moore,ML;Bryan,WM;Fakhoury,SA;Magaard,VW;Huffman,WF;Dayton,BD;Meek,TD;Hyland,L;Dreyer,GB;Metcalf,BW
含有共有逆转录病毒蛋白酶裂解序列 Ser/Thr-X-Y-Tyr/Phe-Pro 的寡肽是纯化重组 HIV-1 蛋白酶的底物，其 Km 在毫摩尔范围内。含有作为良好底物的共有五肽的最小序列是跨越 P4-P3' 残基的七肽。用还原的 Phe-Pro 或 Tyr-Pro 二肽电子等排体或他汀类似物 3-羟基-4-氨基-5-苯基戊酸替代易断裂的二肽，得到了 Ki 值在微摩尔范围内的 HIV-1 蛋白酶抑制剂，其亲和力比相应底物好三个数量级。 HIV-1蛋白酶抑制剂可能为获得性免疫缺陷综合征（AIDS）的治疗提供一种新颖且潜在有用的治疗方法。
Oligopeptides containing the consensus retroviral protease cleavage sequence Ser/Thr-X-Y-Tyr/Phe-Pro are substrates for purified recombinant HIV-1 protease with Km's in the millimolar range. The minimum sequence containing the consensus pentapeptide which serves as a good substrate is a heptapeptide spanning the P4-P3′ residues. Substitution of reduced Phe-Pro or Tyr-Pro dipeptide isosteres or the statine analog 3-hydroxy-4-amino-5-phenylpentanoic acid for the scissile dipeptide afforded inhibitors of HIV-1 protease with Kivalues in the micromolar range, three orders of magnitude better in affinity than the corresponding substrates. Inhibitors of HIV-1 protease may provide a novel and potentially useful therapeutic approach to the treatment of acquired immune deficiency syndrome (AIDS).