Orlando P, Strazzullo G, Carretta F, De Falco M, Grippo P
Istituto Biochimica delle Proteine ed Enzimologia, CNR, Arco Felice, Naples, Italy.
Experientia. 1996 Aug 15;52(8):812-7. doi: 10.1007/BF01923995.
Kelletinin A [ribity pentakis (p-hydroxybenzoate)] (KA), an inhibitor of HTLV-1 replication isolated from Buccinulum corneum, showed a noncompetitive inhibitory activity with respect to the template primer and to dTTP in the poly(rA).oligo(dT)12-18-directed reaction of HIV-1, Mo-MuLV and AMV reverse transcriptases (RT). Analysis of natural and synthetic KA-related compounds showed that the inhibitory activity was strictly related to the structural peculiarities of the molecule. In the presence of DNA as template primer the inhibition mechanism was drastically modified: HIV-1 RT activity was stimulated by low concentrations of KA and was inhibited by increasing the concentration of the compound, while Mo-MuLV and AMV activities were irreversibly inhibited by the formation of a non-reactive complex. The RNase H activities of these RTs were not affected by KA. The results of this study suggest a different mechanism of interaction of Kelletinins with HIV-1 RT compared with other non-nucleoside inhibitors. A possible use of these drugs in combination therapy and in the design of structure-based reverse transcriptase inhibitors is discussed.
从角质滨螺中分离得到的人嗜T淋巴细胞病毒1型（HTLV-1）复制抑制剂凯来亭宁A [核醇五（对羟基苯甲酸酯）]（KA），在HIV-1、莫洛尼鼠白血病病毒（Mo-MuLV）和禽成髓细胞瘤病毒（AMV）逆转录酶（RT）的聚（rA）·寡聚（dT）12-18导向反应中，对模板引物和dTTP表现出非竞争性抑制活性。对天然和合成的与KA相关的化合物进行分析表明，抑制活性与分子的结构特性密切相关。在以DNA作为模板引物的情况下，抑制机制发生了显著改变：低浓度的KA刺激HIV-1 RT活性，而随着化合物浓度增加则受到抑制，而Mo-MuLV和AMV的活性则因形成无反应性复合物而被不可逆地抑制。这些RT的核糖核酸酶H活性不受KA影响。本研究结果表明，与其他非核苷抑制剂相比，凯来亭宁与HIV-1 RT的相互作用机制不同。讨论了这些药物在联合治疗以及基于结构的逆转录酶抑制剂设计中的可能用途。
