Mouscadet J F, Carteau S, Goulaouic H, Subra F, Auclair C
Laboratoire de Physicochimie et de Pharmacologie des Macromolécules Biologiques, CNRS URA 147, Institut Gustave-Roussy, PRII, Villejuif, France.
J Biol Chem. 1994 Aug 26;269(34):21635-8.
Integration of human immunodeficiency virus (HIV) DNA into the genome of host cells is an obligatory step in the replicative cycle of the virus. The overall process is carried out in vitro by a single viral protein, the integrase, which binds to short sequences located at the ends of viral DNA long terminal repeats (LTRs). These end sequences are highly conserved in all HIV genomes and are therefore attractive targets for selective DNA binding compounds. The integrase-binding site located in U3 LTR contains a purine motif, 5'-GGAAGGG-3' which can be selectively targeted by oligonucleotide-intercalator conjugates. Under neutral pH and physiological temperature, these conjugates readily form a stable complex with the viral DNA which involves a short DNA triplex. Triple-helix formation prevents the catalytic functions of the integrase in vitro which results in a sequence-specific inhibition of the U3 integration process.
人类免疫缺陷病毒（HIV）DNA整合到宿主细胞基因组中是该病毒复制周期中的一个必要步骤。整个过程在体外由单一病毒蛋白——整合酶完成，整合酶与位于病毒DNA长末端重复序列（LTRs）末端的短序列结合。这些末端序列在所有HIV基因组中高度保守，因此是选择性DNA结合化合物的有吸引力的靶点。位于U3 LTR中的整合酶结合位点包含一个嘌呤基序5'-GGAAGGG-3'，寡核苷酸嵌入剂缀合物可以选择性地靶向该基序。在中性pH和生理温度下，这些缀合物很容易与病毒DNA形成稳定的复合物，其中涉及一个短的DNA三链体。三链体的形成在体外阻止了整合酶的催化功能，从而导致U3整合过程的序列特异性抑制。
