Synthesis of cyclic peptides containing His and its possibility of brain activating

垂体激素释放激素是在哺乳动物大脑的下丘脑中合成的激素，现在被称为TRH、LHRH、CRH、GHRH等。其中，低分子多肽、TRH和LHRH在结构上表现出相似性。两种多肽均以焦谷氨酸为N端氨基酸，组氨酸为C端，氨基酰胺为C端。我们已经明确了大鼠脑中存在焦咯烷基肽酶，该酶能产生环状肽：组氨酸二酮基哌嗪。这种环肽被认为是一种大脑激活物质。释放激素的生物活性，包括脑激活能力，可能是由于环肽的作用，在这种情况下，我们合成了四个含有组氨酸的多肽，并成功地制备了针对每个环肽的特异性抗体。利用这些抗体，我们希望建立微量测定和免疫组织化学方法，以明确多肽在大脑中的分布。此外，通过垂体细胞培养和免疫印迹的方法，我们还想了解环肽对垂体激素的释放能力。对于这个项目来说，两年时间是不够的。我们现在需要更多的时间，而环肽作为脑激活物质的可能性需要用动物进行活体实验。这个项目最初是在4个成员中计划的，但有两个成员被调换了，无法加入这个项目。只有两个成员开始了这个项目(后来又有另一个成员加入)。所以，我们现在要抓紧时间了。

Pitutitary hormone-releasing hormones which are synthesized in the hypothalamus of the mammalian brain are now known as TRH,LHRH,CRH,GHRH,and so on. Among them, low molecular weight peptides, TRH and LHRH show the structural similarities. Both peptides have pyroGlu as N-terminal amino acid, His, and amino acid amide as C-terminal. We have already cleared that there is pyrogrutamyl peptidase in rat brain and the protease makes cyclic peptide ; histidyl-proline diketopiperazine. This cyclic peptide is supposed to behave as a brain activating substance. Biological activities of the releasing-hormones which show many functions including brain activating ability might be due to the cyclic peptides.Under the circumstances we synthesized four peptides which contain His, then succeeded in making antibodies which have specificities against each cyclic peptide. Using the antibodies we wanted to develop the microdetermination and immunohistochemical methods which can clear the peptide distribution in the brain. Besides those, using pituitary cell culture and western blotting methods, we wanted to know the pituitary hormonereleasing abilities of cyclic peptides. Two years was not enough for this project. We now need more time, and the possibility of cyclic peptides as brain activating substances needs the experiments using animals in vivo.This project was planned among 4 members at first, but two members were tranferred and were not able to join this project. Only 2 members started this project (afterwards another joined). So, we now making haste.