马蹄金素[N-(N-苯甲酰基-L-苯丙氨酰基)-O-乙酰基-L-苯丙氨醇，MTS]是本项目组从民族药马蹄金（Dichondra repens Forst.）中分离得到的具有抗乙肝病毒活性的二肽类化合物。通过100多个马蹄金素结构修饰衍生物的活性测试，表明约40%的衍生物对乙肝病毒DNA复制有抑制作用，一些衍生物的活性较强、选择指数也较高，且未见明显"反跳"现象。鉴于该类衍生物初步药代实验显示其在体内各组织中分布较广，在肝脏组织中的浓度不太高，为提高该类化合物在肝脏病变部位的药物浓度，增强抗乙肝病毒活性，降低不良反应，本项目拟在前期研究基础上，选择5-10个抗乙肝病毒活性较好、选择指数较高的衍生物为结构修饰底物，设计、合成50个以上肝靶向马蹄金素衍生物，并对其进行抗乙肝病毒活性研究，选择其中活性较好的衍生物进行肝靶向性分析和抗乙肝病毒作用机制研究，为该类化合物的深入研究开发提供科学依据。

Matijing-Su [N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol，MTS], a natural anti hepatitis B virus (HBV) derivative of dipeptide, was isolated from ethnic drug Matijing (Dichondra repens Forst.) by our research group. In our previous studies, more than 100 of MTS derivatives were synthesized by structural modification of MTS, and the results of their anti-HBV test showed that some of the synthetic derivatives gave significant inhibition on HBV DNA replication, as well as high selectivity index (SI). In addition, bioactivity test of some derivatives showed significant effect of anti-duck hepatitis B virus without the effect of "back up". The preliminary pharmacokinetic experiments of MTS derivatives showed that it was widely distributed in many organs, and the concentration in liver was low. In this project, to improve the drug delivery to the target tissue and reduce drug distribution to the non-target tissues, as well as to reduce the dosage, and obtain increased therapeutic activity with minimal side effects, more than 50 of liver targeting MTS derivatives will be designed and synthesized by using 5-10 of the MTS derivatives with higher activity as substrates. In addition, the anti-HBV activity of all the synthetic compounds in vitro will be tested. The anti-DHBV activity of the effective derivatives in vivo and their mechanisms of action will be systematically studied. The results of this study will provide a scientific basis for the further studies of this type of anti-HBV derivatives.