Structure-activity relationship of diapause hormone analogs and creation of the potent agonists

在过去的研究中，已经明确了滞育激素（DH）的c端三肽酰胺（PRL-NH_2）是生物活性最低的结构。本研究通过制备DH类似物和分析其生物活性来分析DH侧链基团在活性表达中的作用。结果表明：1)酰胺结构对活性的影响是不可缺少的；2)PRL-NH_2的Arg带正电侧链是必不可少的；3)用酰基修饰PRL-NH_2提高了活性；4)棕榈酰- nh_2和硬脂酰-PRL-NH_2的活性最强。而从蚕蛹头部分离的亲脂肽则增强了DH的活性。该肽的片段类似物对DH酶解有有趣的影响。它通过与底物DH相互作用而不是与酶相互作用来保护激素不被消化。在其他节肢动物中寻找了另一种对DH作用具有类似协同作用的肽，并从熊猫虾（Pandalus borealis）的壳中分离到了pbcp -12.7蛋白，并阐明了其独特的结构和亲脂性。这些结果为改进激素的给药方法提供了提示。

In the past research, it has been clarified that the C-terminal tri-peptide amide (PRL-NH_2) of diapause hormone (DH) is the minimum structure for biological activity.In the present study, the role of the side-chain group of DH for the activity expression was analyzed by preparing the DH analogs and by analyzing the biological activity. The results are : 1) the amide structure is indispensable for the activity, 2) the positively charged side-chain of Arg of PRL-NH_2 is essential, 3) modification of PRL-NH_2 with acyl group enhances the activity, 4) palmitoyl-NH_2 and stearoyl-PRL-NH_2 show the strongest activity among the tested derivatives.While, the lipophilic peptide isolated from the heads of silkmoths enhanced the activity of DH.The fragment analog of the peptide showed interesting effect on enzymic digestion of DH.It protected the hormone from the digestion by interacting not with the enzyme but with the substrate, DH.Another peptide showing the similar synergistic effect on DH action was searched for in the other arthropods, and one protein, Pb CP-12.7, was isolated from the shell of the shrimp, Pandalus borealis, and its unique structure and lipophilic nature were clarified. These results offered the hint to improve the method for dosage of the hormone.