艾滋病是21世纪人类面临的最严重的挑战之一，由于艾滋病病毒具有快速变异和遗传异质性，抗艾滋病药物的研制难度极大。目前临床上使用的抗艾滋病药物主要是蛋白质抑制剂，极易产生耐药性和毒性，所以研制新型的不易产生耐药性的抗艾滋病药物一直是生物医药界的难题之一。TAR RNA序列是HIV病毒的遗传基因区之一，具有高度保守和相对不易变异性，因此成为人们寻找新的抗艾滋病药物设计的非常具有吸引力的新靶点。本项目基于TAR序列的特异性二级结构bulge区域，通过研究双核金属配合物与TAR的磷酸骨架间的选择性相互作用，采用嵌插基团+双核金属相结合的方式来与TAR的bulge区及其lower stem进行选择性识别。本课题的研究结果不仅可以解决以前发展的阳离子小分子与RNA的结合选择性较差的难题，为筛选阻断Tat-TAR相互作用的小分子提供新的设计思路，还可以为发展具有新颖结构的抗艾滋病药物提供新的候选化合物。

HIV is one of the world's most serious health and development challenges in the twenty-first century. However, the development of anti-HIV drugs is extremely difficult because of the fast variation and genetic heterogeneity of the AIDS virus. Currently developed anti-HIV drugs are mainly protein inhibitors. As to the resistance and toxicity of those drugs, inventing a new type of non-resistance anti-HIV drug still remains a challenge in biomedical industry. TAR RNA is one of the highly conservative and relatively stable genetic regions in HIV virus, which makes it an attractive target for developing new anti-HIV drugs. We propose to target the specific secondary structure of TAR RNA -- the bulge region, by developing a dinuclear metal complex binding with the phosphate backbone, and then use the combination of dinuclear metal -- intercalative complex to selectively bind with the bulge and lower stem of TAR RNA. The result of this proposal will overcome the low specificity of those developed cationic molecular drugs, and will also provide a new strategy for designing small organic molecules blocking Tat-TAR interaction by delivering new candidate compounds for the development of new anti-HIV drugs.