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

在过去的研究中，滞育激素的C末端三肽酰胺(PRL-NH_2)是生物活性的最小结构，本研究通过制备滞育激素类似物并对其进行生物活性分析，分析了滞育激素侧链基团对活性表达的作用。结果表明：1)酰胺结构是必需的，2)精氨酸氨基的正电侧链是必需的，3)用酰基修饰PRL-NH_2的活性增强，4)棕榈酰基-NH_2和硬脂酰基-PRL-NH_2的活性最强。从蚕蛾头部分离的亲脂肽对脱氢酶的活性有促进作用。该片段类似物对脱氢酶有很好的酶促消化作用。在其他节肢动物中发现了另一种具有类似协同作用的多肽，并从北方对虾的壳中分离到一种蛋白质，命名为PbCP-12.7，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线索。

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.