裝訂脯胺酸寡肽之合成與其結構穩定性

The Synthesis and Structure Stability of Stapled Polyproline Peptides

曾文秀(Wen-Hsiu Tseng)

指導教授 ： 王聖凱

國立清華大學/理學院/化學系所/碩士(2018年)

摘要

在生醫領域中，已發展出數種胜肽藥物，或是以胜肽作為骨架，形成藥物載體。但在生物體內，胜肽易受到酵素辨認，而失去活性，目前發展出裝訂胜肽(stapled peptide)的技術來提升生物體內胜肽的壽命。我們嘗試於脯胺酸多肽螺旋II (Polyproline Helix II, PP II)結構上進行裝訂，利用控制裝訂鏈(Linker)的長度，與改變裝訂位置，觀察此種設計對PP II結構影響。經由交叉測試後，得知i, i+3裝訂會比i, i+2與i, i+1裝訂容易成功。和寡脯胺酸多肽相比，在正丙醇溶液中，可以發現不同長度，位置的裝訂方式會影響結構。除了透過CD光譜鑑定結構外，也使用GROMACS動力學軟體，來模擬研究中合成出來的數種裝訂胜肽。

關鍵字

脯胺酸寡肽 ； 裝訂胜肽 ； 脯胺酸多肽螺旋 ； 圓二色性 ； 銅催化疊氮-炔類[3+2]環化加成 ； GROMACS

並列摘要

In recent years, many drugs and carriers based on peptides has been developed. However, drug design based on peptide has a critical disadvantage that they may be degraded by enzymes in organism. For this issue, peptide stapling is one practical solution to extend the lifespan of peptides. While polyproline peptides have unique structure for various applications, we “stapled” polyproline peptide systematically to investigate the effects on polyproline helix II (PP II) structure by change linker length and the locations of stapled residues. From circular dischroism (CD) analysis, we found that stapling at i, i+3 residues of polyproline peptides stabilizing PP II structure better than other locations at i, i+1 and i, i+2. Compared to normal polyproline, the PP II structure stapled polyproline is also affected by the staple length in n-propanol. In addition to CD spectrum, we use GROMACS software to simulate the molecular dynamics of stapled peptides in water.

並列關鍵字

Polyproline ； Stapled Peptide ； Polyproline Helix II ； Circular Dischroism ； CuAAC ； GROMACS

參考文獻

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