苯並三唑銜接劑於多元胜肽結合物之合成應用

Synthesis applications of Bt-linker in diverse peptide-conjugates

鍾佳陞(Chia-Sheng Chung)

指導教授 ： 陳信允

高雄醫學大學/生命科學院/醫藥暨應用化學系碩士班/碩士(2019年)

摘要

本研究以苯並三唑作為銜接劑，並修飾在固體支持物 (樹脂)上，再以 Fmoc策略進行目標胜肽之合成，將四條具有功能的胜肽 (D6, R7, RGD, DEA)合成完成後，透過親核性取代方式將生物素或辛伐他汀與胜肽鍵結，並將樹脂移除，再經去除保護基後成功合成出三個具有生物素修飾之胜肽結合物 (D6-biotin、R7-biotin、DEA-biotin)，可惜三個具藥物鍵結之胜肽結合物 (R7-Sim、D6-Sim、RGD-Sim)未能得到成果。透過高效能液相層析儀證明各產物之純度；經由核磁共振光譜儀、電噴灑質譜儀、介質輔助雷射脫附電離質譜儀測定證明其結構。利用生物素與鏈親和素彼此強烈交互作用的特性，期待日後將生物素結合物運用於與鏈親和素修飾衍生物結合。
本論文為模型研究，藉由苯並三唑為銜接劑的固相胜肽合成方法，提供後續相關需求─方便有效率的製備策略。

關鍵字

固相胜肽合成法 ； 苯並三唑 ； 生物素 ； 辛伐他汀

並列摘要

In this study, benzotriazole was used as a linker and modified on a solid support (resin). The synthesis of the target peptide was carried out by the Fmoc strategy. After synthesizing four functional peptide (D6, R7, RGD, DEA), the biotin or simvastatin was bonded to the peptide through nucleophilic substitution, and the resin cleavage was accompanied. Then after removal of the protecting group, three biotin-modified peptide conjugates (D6-biotin, R7-biotin, DEA-biotin) had been successfully synthesized, unfortunately, three drug-bonded peptide conjugates (R7-Sim, D6-Sim, RGD-Sim) could not be achieved. The purity of each product was confirmed by High Performance Liquid Chromatography; and their structure were identified by Nuclear Magnetic Resonance, ElectroSpray Ionization Mass Spectrometry, and Matrix-Assisted Laser Desorption/Inoization Mass Spectrometry. According to the characteristics of strong interaction between biotin and streptavidin, it is expected that biotin conjugates will be used in combination with streptavidin-modified derivatives.
This thesis is a model study, which demonstrated a convenient and efficient strategy for the preparation of subsequent related requirements through the benzotriazole containing solid phase peptide synthesis approach.

並列關鍵字

Solid phase peptide synthesis ； Benzotriazole ； Biotin ； Simvastatin

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