具有多個結合位的蛋白質在與對應醣基進行結合的時候，醣基間的距離與位置會對多價性結合造成關鍵性的影響。在生物系統中這影響醣-蛋白作用強弱與細胞的辨識。而如果能夠在細胞膜上控制特定醣基相對應的距離，將能影響該細胞對此類蛋白的結合能力，並對其操作。
本論文中主要利用聚脯胺酸具規律的剛性PPII結構作為骨架設計。第一部分以不同數量和長度的碳鏈作為疏水錨，以共軛焦顯微鏡與流式細胞儀觀測得到這些合成多肽在細胞膜的附著程度。以此驗證疏水錨設計帶來的性質變化，實驗後顯示適當改變碳鏈的長度得到不同的附著效果。而在第二部分中，利用第一部分的結論而設計具有複數疏水碳鏈的多肽，並在合成時引入不同官能基側鏈的脯胺酸單體，得以在多肽上設計的位置修飾上特定醣基。以這些具一定細胞膜結合能力的多肽進行細胞實驗嘗試確認它們是否能為細胞帶來更好的蛋白質結合效果。雖然因為部分未完成的實驗無法做出最終結論，但已開發出一種可行的合成策略。若未來能在細胞上成功產生不同的醣-蛋白結合能力，將對設計蛋白質與細胞表面醣基交互作用相關影響的工具有所幫助。

Multivalent interactions involved in strengths of carbohydrate – protein interactions and the recognition in biological system. The positions and the distances between glycans have great influence on binding to proteins with multiple binding sites. Therefore, if we can precisely control glycan ligands at specific positions on cell membrane, we will be able to better manipulate such interactions on cell.
In this research, we used rigid and well-defined polyproline II helix as scaffolds to support glycan ligands. In the first part, we introduced alkyl chains of different lengths as hydrophobic anchors for polyproline to bind to cell membrane. We evaluated the binding strength of these peptides on cell membrane with confocal microscopy and flow cytometry, and found that appropriate adjustment on the the length of hydrophobic chains alters cell binding. In the second part, we took the design from the first part, and introduced glycan ligands at specific positions. Although the measurement of carbohydrate - protein interactions on control distance was not achieved, this research provides a synthetic strategy for polyproline scaffolds that bind to cell membrane while controlling glycan ligand distance. The information provided could benefit future recognition research on cell membrane.

摘要
目錄
第一章、緒論 1
1.1 前言 1
1.2 醣類與蛋白質的交互作用 2
1.2.1 Con A (Concanavalin A) 2
1.2.2 2G12 3
1.3 多價交互作用 4
1.4 聚脯胺酸多肽 8
1.4.1 聚脯胺酸多肽的結構 8
1.4.2 聚脯胺酸多肽的特性及應用 9
1.5 細胞膜上的醣類修飾 11
1.6 固相多肽合成 13
1.7 實驗設計 15
第二章、結果與討論 19
2.1 多肽合成構築單元合成 19
2.1.1 脯胺酸構築單元合成 19
2.1.2 疏水錨脂質分子合成 20
2.2 疏水錨脯胺酸多肽 21
2.2.1 固相多肽合成 21
2.2.2 CuAAC反應組合疏水錨分子 23
2.2.3 細胞附著實驗 24
2.3 疏水錨醣脯胺酸多肽 30
2.3.1 固相多肽合成與醣基修飾 30
2.3.2 圓二色光譜分析 35
2.3.3 細胞實驗 36
2.4 結論 38
第三章、實驗方法與材料 39
3.1 General Methods for Synthesis and Characterization 39
3.2 Synthesis of Peptide Building Blocks and Hydrophobic Anchor 40
3.3 Synthesis of Peptide and Assembling 48
3.3.1 Solid phase peptide synthesis 48
3.3.2 N-terminal carboxyfluorescein conjugation 51
3.3.3 Hydrophobic anchor assembling 53
3.3.4 Alloc deprotection 60
3.3.5 Alkyne containing linker conjugate 62
3.3.6 Glycan conjugation on scaffold 64
3.4 Cell Culture and Experiment Method 66
3.4.1 Cell culture 66
3.4.2 Confocal microscopy 67
3.4.3 Flow cytometry 68
第四章、參考資料 69
附錄

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