【作者】 吕国华；

【导师】 董守良；

【作者基本信息】 兰州大学 ， 生物化学与分子生物学， 2009， 硕士

【摘要】 目的:对牛肾上腺髓质肽8-22(BAM8-22:Val-Gly-Arg-Pro-Glu-Trp-Trp-Met-Asp-Tyr-Gln-Lys-Arg-Tyr-Gly)进行首次空间结构的研究,并进一步结合已有的生物活性数据从三维结构水平上分析BAM8-22及其一系列片段肽的构效关系。方法:首先通过二维核磁共振技术测定了BAM8-22在水溶液中的空间三维构象,然后再通过20 ns的水中分子动力学模拟补充观察BAM8-22的动力学特征;接着,在BAM8-22核磁结构的基础上,对其片段肽BAM13-22,BAM15-22,BAM8-18,BAM8-20分别进行20 ns的水中分子动力学模拟,分析观察它们的结构变化与稳定性。结果:水溶液中的BAM8-22在肽段BAM12-20是一个相对稳定的α-螺旋结构,两端氨基酸残基是一个比较柔性的构象;而其片段肽BAM13-22的α-螺旋大约稳定在BAM15-20;BAM15-22的α-螺旋完全消失;BAM8-18的α-螺旋大约稳定在BAM12-16;BAM8-20的α-螺旋大约稳定在BAM12-18。结论:通过得到的BAM8-22的溶液三维结构与动力学特征及其片段肽的空间构象的变化信息,再结合已有的功能活性数据进行构效关系分析发现BAM12-20位的α-螺旋对维持BAM8-22的生物活性是非常必需的。所有这些结构研究,不仅能够指导合理改造BAM8-22,进而设计活性更好的类似物,同时也能给进一步研究BAM8-22与Mrg受体的相互作用机制提供结构基础。更多还原

【Abstract】 Objective: To shed first light on the structural information of Bovine adrenal medullary peptide BAM8-22 (Val-Gly-Arg-Pro-Glu-Trp-Trp-Met-Asp-Tyr-Gln-Lys-Arg-Tyr- Gly), and to gain more detail insight into conformation-activity relationship of BAM8-22 and its truncated peptides on the basis of available function activity study. Methods: The solution structure of BAM8-22 was determined by 2D NMR in water. The dynamic features of BAM8-22 were further investigated by molecular dynamics simulation for 20 ns. Furthermore, the solution structure of BAM8-22 was used to study the conformation characterization of truncated peptide BAM13-22, BAM15-22, BAM8-18 and BAM8-20 by molecular dynamics simulation for 20 ns.Results: BAM8-22 possesses a relatively well-definedα-helix structure during approximately BAM12-20 in aqueous solution, whereas the both termini show highly flexibility. Theα-helix structure of BAM13-22, BAM8-18 and BAM8-20 were spanning from BAM15-20, BAM12-16 and BAM12-18, respectively, while theα-helix structure in BAM15-22 was completely disappeared. Conclusion: From the three-dimentional structure and dynamics features of BAM8-22 and conformational characterization of its truncated peptides, combined with the available functional activity data, it seems reasonable to conclude that the well-definedα-helix structure plays an essential role on the bioactivcity of BAM8-22. All the biophysical data obtained in the current work provides important structural fundation of BAM8-22 which would be helpful to rationally design its analogues and also could be uesd as structural model for further studying its interaction with Mrg receptors.更多还原