Divita G, Restle T, Goody R S, Chermann J C, Baillon J G
Max-Planck Institut für Medizinische Forschung, Abteilung Biophysik, Heidelberg, Federal Republic of Germany.
J Biol Chem. 1994 May 6;269(18):13080-3.
Based on presently available information on the structure of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, peptides have been synthesized which correspond to the sequence of a particular region of the protein involved in formation of the active heterodimeric form of the enzyme. Several peptides that are 15-19 amino acids long and that are derived from the so-called connection domain of the reverse transcriptase are able to inhibit dimerization of the enzyme and thus inhibit development of its enzymatic activities. In particular, a tryptophan-rich 19-mer corresponding to residues 389-407 was relatively efficient, showing an apparent dissociation constant in the micromolar range for one or both of the subunits. The sequence of this region is identical for both subunits, since one (molecular mass of 51 kDa) is the proteolytic product of the other (molecular mass of 66 kDa). Dissociation of the preformed heterodimer could not be induced by the peptides, but increasing concentrations reduced the rate of dimerization in a concentration-dependent manner until it became immeasurable at high concentrations. The results suggest that inhibition of dimerization of reverse transcriptase is an attractive approach to chemotherapeutic intervention in HIV infection and that further development of peptide-based inhibition strategies is worth pursuing.
基于目前有关人类免疫缺陷病毒1型（HIV-1）逆转录酶结构的可用信息，已合成了与该酶活性异二聚体形式形成过程中涉及的蛋白质特定区域序列相对应的肽。几种长度为15 - 19个氨基酸且源自逆转录酶所谓连接域的肽能够抑制该酶的二聚化，从而抑制其酶活性的发展。特别是，对应于389 - 407位残基的富含色氨酸的19肽相对有效，对于一个或两个亚基，其表观解离常数在微摩尔范围内。该区域的序列在两个亚基中是相同的，因为一个亚基（分子量为51 kDa）是另一个亚基（分子量为66 kDa）的蛋白水解产物。这些肽不能诱导预先形成的异二聚体解离，但浓度增加会以浓度依赖的方式降低二聚化速率，直到在高浓度下变得无法测量。结果表明，抑制逆转录酶的二聚化是HIV感染化疗干预的一种有吸引力的方法，基于肽的抑制策略的进一步开发值得 pursued。 （最后一个词“pursued”你原文可能有误，正确应该是“pursuing”，这里暂且按照你给定的翻译，若有误请修正）
