Ménard A, Leonard R, Llido S, Geoffre S, Picard P, Berteau F, Precigoux G, Hospital M, Guillemain B
INSERM Unité 328, fondation Bergonié, Bordeaux, France.
FEBS Lett. 1994 Jun 13;346(2-3):268-72. doi: 10.1016/0014-5793(94)00488-9.
In view of the close similarity between bovine leukemia virus (BLV) and human T-cell leukemia virus type I (HTLV-I) we investigated the possibility of developing specific inhibitors of the proteases of these retroviruses using the purified enzyme from BLV. We tested the ability of this protease to specifically cleave various short oligopeptide substrates containing cleavage sites of BLV and HTLV-I proteases, as well as a recombinant BLV Gag precursor. The best substrate, a synthetic decapeptide bearing the natural cleavage site between the matrix and the capsid proteins of BLV Gag precursor polyprotein, was used to develop an inhibition assay. We determined the relative inhibitory effect of synthetic Gag precursor-like peptides in which the cleavable site was replaced by a non-hydrolyzable moiety. The encouraging inhibitory effect of these compounds indicates that potent non-peptidic inhibitors for retroviral proteases are not unattainable.
鉴于牛白血病病毒（BLV）与人类I型T细胞白血病病毒（HTLV-I）极为相似，我们利用从BLV中纯化得到的酶，研究了开发这些逆转录病毒蛋白酶特异性抑制剂的可能性。我们测试了这种蛋白酶特异性切割各种短寡肽底物的能力，这些底物包含BLV和HTLV-I蛋白酶的切割位点，以及重组BLV Gag前体。最佳底物是一种合成十肽，其带有BLV Gag前体多蛋白的基质蛋白和衣壳蛋白之间的天然切割位点，用于开发抑制试验。我们测定了可切割位点被不可水解部分取代的合成Gag前体样肽的相对抑制作用。这些化合物令人鼓舞的抑制作用表明，开发有效的逆转录病毒蛋白酶非肽类抑制剂并非无法实现。
