多肽药物合成任务书
2020-04-22 19:45:58
1. 毕业设计(论文)的内容和要求
内容:熟悉丝氨酸、苏氨酸对接法的背景、基本原理及操作、多肽固液相合成的基本方法并能独立合成短肽,探究ligation模板反应条件以及用ligation的方法进行合成肽片段之间偶联。
要求:能够熟悉并独立完成以上实验的操作,了解基本背景、基本原理,并能够独立分析实验过程中遇到的问题。
2. 参考文献
[1]Lee C L, Li X C. Serine/Threonine Ligation for the Chemical Synthesis[J]. Current Opinion in Chemical Biology, 2014, 22: 108~114. [2]Kemp D S. The Amine Capture Strategy for Peptide Bond Formation an Outline of Progress[J]. Biopolymer, 1981, 20(9): 1793~1804. [3]Liu C F, Tam J P. Peptide Segment Ligation Strategy without Use of Protecting Groups[J]. Proc Natl Acad Sci, 1994, 91: 6584~6588. [4]Chen X X, Gao F, Wang Q, et al. Design, Synthesis and Biological Evaluation of Paclitaxel-mimics Possessing Only the Oxetane D-ring and Side Chain Structures[J]. Fitoterapia, 2014, 92: 111~115. [5]Gosain R, Norrish A M, Wood M E. A Concise Method for the Functionalisation of Ethanolamine α to Nitrogen Using Free Radical Methodology[J]. Tetrahedron, 2001, 57: 1399~1410. [6]Levine P M, Craven T W, Bonneau R, et al. Chemoselective Fragment Condensation between Peptide and Peptidomimetic Oligomers[J]. Org Bio Chem, 2013, 11: 4142~4146. [7]Li X C, Lam H Y, Zhang Y F, et al. Salicylaldehyde Ester-Induced Chemoselective Peptide Ligations: Enabling Generation of Natural Peptidic Linkages at the Serine/Threonine Sites[J]. Org Lett, 2010, 12(8): 1724~1727. [8]Ruysbergh E, Hecke K V, Stevens C V, et al. Synthesis of 1,4-Oxazepane-2,5-diones via Cyclization of Rotationally Restricted Amino Acid Precursors and Structural Reassignment of Serratin[J]. J Org Chem, 2017, 82: 6210~6222. [9]Li X C, Xu C, Lam H Y, et al. Convergent Synthesis of MUC1 Glycopeptides via Serine Ligation[J]. Chem Commun, 2013, 49: 6200~6202. [10]Li T L, Liu H, Li X C. Chemical Synthesis of HMGA1a Proteins with Post-translational Modi#64257;cations via Ser/Thr Ligation[J]. Org Lett, 2016, 18: 5944~5947. [11]Lam H Y, Zhang Y F, Li X C, et al. Total Synthesis of Daptomycin by Cyclization via a Chemoselective Serine Ligation[J]. J Am Chem Soc, 2013, 135: 6272~6279. [12]Lin D A, Lam H Y, Li X C, et al. Structure-activity Relationship of Daptomycin Analogues with Substitution at (2S, 3R) 3-Methyl Glutamic Acid Position[J]. Bioorganic Medicinal Chemistry Letters, 2017, 27: 456~459. [13]Wong C T, Lam H Y, Li X C. Effective Synthesis of Cyclic Peptide Yunnanin C and Analogues via Ser/Thr Ligation(STL)-mediated Peptide Cyclization[J]. Tetrahedron, 2014, 70: 7770~7773. [14]Lee C L, Liu H, Li X C, et al. Enabling N#8209;to#8209;C Ser/Thr Ligation for Convergent Protein Synthesis via Combining Chemical Ligation Approaches[J]. J Am Chem Soc, 2016, 138: 10477~10484.
3. 毕业设计(论文)进程安排
3月份:熟悉实验室并能够独立完成论文相关的简单实验操作 4月份:能够独立完成论文相关的大部分实验工作及分析实验过程中遇到的问题 5月份:对论文实验的完善、总结、论文的撰写
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