1. 毕业设计（论文）的内容和要求

1.文献查阅 从查阅文献着手，在中国期刊网，维普数据库，超星数字图书馆，美国化学学会(acs)数据库，ca，sci等检索资源上查阅有关kras-pde6δ的相关文献。

2．文献阅读及综述 阅读与课题相关的文献，了解kras-pde6δ抑制剂设计合成的基本情况、方法和国内外的研究动态，撰写文献综述。

3．明确实验任务，拟定实验方案 根据所查阅文献的内容，确定实验内容及方案，拟定科学可行的研究计划。

2. 参考文献

Yan Jiang,#8224;,#167; Chunlin Zhuang,#8224;,#167; Long Chen,#8224;,#167; Junjie Lu,#8224; Guoqiang Dong,#8224; Zhenyuan Miao,#8224; Wannian Zhang,#8224; Jian Li,#8225; and Chunquan Sheng*,#8224; J. Med. Chem. 2017, 60, 9400-9406 Long Chen,#8224; Chunlin Zhuang,#8224; Junjie Lu,#8224; Yan Jiang, and Chunquan Sheng* J. Med. Chem. 2018, 61, 2604#8722;2610 Nature Reviews Drug Discovery | AOP, published online 21 June 2013; doi:10.1038/nrd4054 Gunther Zimmermann1*, Bjo #168;rn Papke2*, Shehab Ismail3*, Nachiket Vartak2, Anchal Chandra2, Maike Hoffmann4, Stephan A. Hahn4, Gemma Triola1, Alfred Wittinghofer3, Philippe I. H. Bastiaens2,5 Herbert Waldmann1,5 3 0 M AY 2 0 1 3 | V O L 4 9 7 | N AT U R E | 6 4 1 Martin W. Rowbottom,* Gretchen Bain, Imelda Calderon, Taylor Lasof, David Lonergan, Andiliy Lai, Fei Huang, Janice Darlington, Patricia Prodanovich, Angelina M. Santini, Christopher D. King, Lance Goulet, Kristen E. Shannon, Gina L. Ma, Katherine Nguyen, Deidre A. MacKenna, Jilly F. Evans, and John H. Hutchinson J. Med. Chem. 2017, 60, 4403#8722;4423 Ismail, S. A.; Chen, Y. X.; Rusinova, A.; Chandra, A.; Bierbaum, M.; Gremer, L.; Triola, G.; Waldmann, H.; Bastiaens, P. I.;Wittinghofer, A. Arl2-GTP and Arl3-GTP regulate a GDI-liketransport system for farnesylated cargo. Nat. Chem. Biol. 2011, 7, 942#8722;949. Chen, Y. X.; Koch, S.; Uhlenbrock, K.; Weise, K.; Das, D.;Gremer, L.; Brunsveld, L.; Wittinghofer, A.; Winter, R.; Triola, G.;Waldmann, H. Synthesis of the Rheb and K-Ras4B GTPases. Angew.Chem., Int. Ed. 2010, 49, 6090#8722;6095. Zhang, H.; Liu, X. H.; Zhang, K.; Chen, C. K.; Frederick, J. M.; Prestwich, G. D.; Baehr, W. Photoreceptor cGMP phosphodiesterase delta subunit (PDEδ) functions as a prenyl-binding protein. J. Biol. Chem. 2004, 279, 407#8722;413. Nancy, V.; Callebaut, I.; El Marjou, A.; de Gunzburg, J. The delta subunit of retinal rod cGMP phosphodiesterase regulates the membrane association of Ras and Rap GTPases. J. Biol. Chem. 2002, 277, 15076#8722;15084. Nikolova, S.; Guenther, A.; Savai, R.; Weissmann, N.; Ghofrani, H. A.; Konigshoff, M.; Eickelberg, O.; Klepetko, W.; Voswinckel, R.; Seeger, W.; Grimminger, F.; Schermuly, R. T.; Pullamsetti, S. S. Phosphodiesterase 6 subunits are expressed and altered in idiopathic pulmonary fibrosis. Respir. Res. 2010, 11, 146. Tao, Y.; Gu, Y. J.; Cao, Z. H.; Bian, X. J.; Lan, T.; Sang, J. R.;Jiang, L.; Wang, Y.; Qian, H.; Chen, Y. C. Endogenous cGMPdependent protein kinase reverses EGF-induced MAPK/ERK signal transduction through phosphorylation of VASP at Ser239. Oncol. Lett. 2012, 4, 1104#8722;1108. Dai, H.; Song, D.; Xu, J.; Li, B.; Hertz, L.; Peng, L. Ammoniainduced Na,K-ATPase/ouabain-mediated EGF receptor transactivation, MAPK/ERK and PI3K/AKT signaling and ROS formation cause astrocyte swelling. Neurochem. Int. 2013, 63, 610#8722;625.

3. 毕业设计（论文）进程安排

2018.12.21-2019.01.12 熟悉反应原理和实验操作，查阅文献，确定课题，撰写任务书2019.01.13-2019.03.04 确定实验方案，对课题进行初步实验，完成开题报告2019.03.05-2019.03.10 对前一阶段研究内容进行中期汇报，完成中期自检，确定下一步实验方案2019.03.11-2019.03.15 扩展课题研究范围，改进实验方案，对数据整理分析，撰写论文2019.03.16-2019.05.15 完善毕业论文，补充数据，定稿