醣類與蛋白質間作用力相對於蛋白質與蛋白質間作用力較弱，因此以多價交互作用啟動生理反應。若以合成的分子骨架連接醣類配體，可對於其多價交互作用力與選擇性進一步研究。本論文中，由於脯胺酸多肽螺旋在水溶液中構形穩定且有規律性，較具有剛性，會維持polyproline helix II(PPII helix)的結構，可用於調控配基間的距離。因此將脯胺酸多肽分子骨架修飾全氟烷基，用於與氟表面之作用，並且利用多肽上丙炔氧基以銅(I)催化疊氮炔類環化加成反應(Cu(I)catalyzed Azide alkyne Huisgen cycloaddition, CuAAC)，測試醣類配體連接到此多肽的效果。
全氟烷基數量是多肽與氟表面間作用力的關鍵。固相多肽合成(Solid phase peptide synthesis)不同含氟碳鏈數量的多肽，發現全氟烷基數量越多的多肽與氟表面間的結合力越好。同時，脯胺酸多肽上炔基利用CuAAC反應與醣結合，合成醣肽。由於醣類是最後才用環化加成與多肽結合，因此未來可直接改變不同的醣，得到不同的醣肽，便可與不同的蛋白質測試。
在論文中並研究全氟烷基多肽的特性，透過動態光散射(DLS)、粒徑篩析高效液相層析儀(size exclusion HPLC)、掃描式電子顯微鏡(SEM)、穿透式電子顯微鏡(TEM)、圓二色光譜儀(CD)、共軛焦顯微鏡 (confocal microscope) 觀察多肽構形、平均粒徑變化與多肽全氟烷基數量之關聯性，發現全氟烷基數量越多，能穩定聚脯胺酸多肽polyproline helix II結構，並造成較大聚集程度。藉由全氟烷基多肽研究，我們了解此類化合物的合成與性質，有助未來關於此類化合物之應用。

The interaction between carbohydrate and protein is generally weaker than protein protein interaction. To compensate that, nature uses polyvalent interaction to initiate physiological functions. To study these interactions, a molecular scaffold will be a useful tool to support carbohydrate ligands. Since polyproline forms stable polyproline helix II structure in aqueous solution, this peptide can be used to control the distance between carbohydrate ligands due to its rigidity. In this thesis, we study the synthesis and properties of fluorous polyproline peptides because fluorous interaction allows connection of fluorous peptides to fluorous surface. In addition, alkyne groups are also introduced to allow ligand conjugation on peptide through Azide-alkyne Huisgen cycloaddition addition(CuAAC)
The number of fluorous tag is the key to interact with fluorous slide. Solid phase peptide synthesis was applied to synthesize peptides having different numbers of fluorous tags. We found that the peptide with more fluorous tag better stabilize the polyproline helix II struture. In addition, we demonstrate sugar can be conjugated to fluorous polyproline peptides bearing alkyne groups through Azide alkyne Huisgen cycloaddition reaction. This design would allow easily change of glycan ligands to interact with different proteins.
In the study of fluorous peptide aggregation, dynamic light scattering, size exclusion HPLC, electron microscopy (SEM, TEM), confocal microscopy, and circular dichroism are used to observe the connection between the change of particle size and the design of fluorous polyproline peptide. The number the fluoro-tag has, affects degree of aggregation to these peptides. This study in synthesis and property of fluorous polyproline peptides would help us to understand these unique peptides and may benefit in future applications.

中文摘要 ii
Abstract iv
目錄 viii
圖目錄 xi
流程目錄 xiv
式目錄 xv
表目錄 xv
第一章 緒論 1
1-1. 醣類與蛋白質交互作用¹ 1
1-2. 多價交互作用 3
1-3. 微陣列分析 7
1-4. 脯胺酸多肽的特性與應用 9
1-5. 氟烷化物 10
1-5-1. 氟烷化物分類與分離方式 12
1-5-2. 氟標記在生物分子上應用 12
1-5-3. 全氟烷基多肽自我聚集 14
1-6 微脂體形成與特性44 15
1-7 逆微胞(reverse micelle) 17
介面活性劑(surfactant)是一種同時具有親水端及疏水端的兩性分子，依照其親水性帶電性的不同，分為四大類: 陰離子性，陽離子性，非離子性，兩性。 17
1-8. 固相多肽合成53 19
1-9. 疊氮和炔類的[3+2]環化加成 22
1-10 立體電子效應 23
1-11. 圓二色光譜儀60 24
1-12. 動態光散射 (Dynamic Light Scattering, DLS)62 26
1-13. 電子顯微鏡 27
1-14 研究動機與實驗設計 28
第二章 結果與討論 31
2-1. 化學合成實驗 32
2-1-1 合成脯胺酸-氟標記化合物 32
2-1-2 合成脯胺酸-氟標記多肽 34
2-1-3 多肽與螢光分子耦合 39
2-1-4 疊氮炔環化加成 40
2-2 微陣列晶片測試 41
2-3 多肽性質實驗 44
2-3-1. Far UV CD 光譜 44
2-3-2 動態光散射實驗 54
2-3-3 共軛焦顯微鏡(Confocal Microscope) 59
2-3-4 粒徑篩析高效液相層析(Size exclusion HPLC) 68
2-3-5 掃描式電子顯微鏡(Scanning Electron Microscope, SEM ) 71
2-3-6 穿透式電子顯微鏡(Transmission Electron Microscope, TEM) 77
第三章 結論 82
第四章 實驗部分 85
4-1. 實驗儀器 85
4-2. 化學合成實驗 87
4-2-1. 合成脯胺酸-氟標記化合物 87
4-2-2. 合成脯胺酸-氟標記多肽(SPPS) 97
4-2-3. Cy3 coupling 99
4-2-4. Copper Catalyzed Azide-Alkyne Cycloaddition 99
4-3. 氟多肽性質實驗材料與方法 100
4-3-1. 圓二色光譜儀量測 100
4-3-2. 掃描式電子顯微鏡(scanning electron microscope, SEM) 101
4-3-3. 穿透式電子顯微鏡(transmission electron microscopy, TEM ) 101
4-4. 參考文獻 102
附圖目錄 1
HPLC圖譜 3
附錄、NMR光譜 5

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