Function and Structure Analyses of Anticoagulant and Vasodilator Isolated from the Salivary Glands of Blood Sucking Insects, and Development of Novel Medicine

吸血昆虫的唾液腺含有一些生物活性物质，可以控制宿主动物的凝血和血管，以帮助持续的血液摄取。在本研究中，我们从腺体中寻找这些生物活性分子，并对其分子结构、活性和作用方式进行分析，以阐明这些分子的生物学意义，并试图开发一种新型药物材料。我们建立了这些动物的唾液腺EST数据库，分别对179、120和218个新序列的分子进行了分析。通过杆状病毒表达系统的表达和活性分析，我们分别鉴定了5个、3个和3个新的生物活性分子，其中一个是从按蚊的唾液腺中分离和鉴定的。我们发现，Hamadalin通过将凝血级联的XII因子和高分子激肽原结合到这些分子带负电荷的表面的结合部位来抑制凝血级联和高分子激肽原，从而抑制凝血级联和bladikinin的产生从而抑制炎症。哈马达林有可能成为开发新型抗凝抗炎药物的先导分子。

The salivary glands of blood sucking insects contain some bio-active substances to control blood coagulation and blood vessel of host animals for assisting a continuous blood feeding. In this study, we searched these bio-active molecules from the glands and analyzed the molecular structure, activity and mode of action to elucidate the biological significance of these molecules, and tried to develop a material for novel medicine.We used two blood sucking insects, Triatoma infestans (Ti) and Anopheles stephensi (As), and the tick, Haemaphisalis bispinosa (Hb) as material animals. We established the data bases of salivary gland EST of these animals, and analyzed 179, 120 and 218 molecules with novel sequences, respectively. We identified 5, 3, and 3 novel bio-active molecules respectively after expression by baculo virus expression system and analysis of activities.'Hamadarin', one of them is isolated and identified from the salivary glands of anopheline mosquito As. We found hamadalin inhibits factor XII of coagulation cascade and high molecular weight kininogen by binding them to the binding sites of these molecules to negative charged surface, and as results inhibits coagulation cascade and generation of bladikinin and therefore inflammation. Hamadalin has a possibility to be a lead molecules developing novel anticoagulant and anti-inflammation drug.