藉由親核性樹脂設計與合成專一性前列腺抗體-聚離胺酸兩性樹枝狀高分子並自組裝作為標靶傳送及診斷治療.

Design and Synthesis of Amphiphilic Prostate Specific Antibody-Poly-L-Lysine Dendrimers Using a Nucleophilic Cleavable Resin and Self-Assembly for Target Delivery of Theranostics.

柯力恆(Mavela Cleopus Mahlalela)

指導教授 ： 高佳麟

高雄醫學大學/生命科學院/醫藥暨應用化學系碩士在職專班/碩士(2017年)

摘要

樹枝狀高分子在未來有潛力成為生物性分子上的研究趨勢，因其設計完善的結構，和多功能性表面。藉由具分子的設計，有能力包覆或以共價鍵結疏水和親水的化合物。在樹枝狀高分子的表面修飾胺基酸或胜肽是一種胜肽模擬的方法，並可應用於臨床研究中。但是在巨分子上，量產大代數高分子是一大困難。因此克服此一困難的方法之一是先合成小代數，再藉由自組裝形成大代數的樹枝狀高分子。而且有研究指出，相較於大代數，小代數的毒性較小。不論在生物領域中廣泛的應用，高分子於生物體系統中受限於高毒性此一問題。在實驗室先前研究中，將rink amide樹脂以間位雙氨基苯甲酸修飾，形成疊氮-炔環化反應，最後以親和性試劑切除。並以此方法設計具自組裝特性之巨分子。我們以Fmoc固相合成法合成具有兩性結構的前列腺專一性抗體和低代數的賴氨酸樹枝狀高分子。希望此合成能為巨分子在生物上的應用建立更好的方法.

關鍵字

樹枝狀高分子 ； 自組裝 ； 性前列腺抗體

並列摘要

In this work, we present a method for the synthesis and design of system with self-assembly properties. Using a nucleophilic cleavable rink amide resin modified with a 3,4-diaminobenzoyl (Dbz) linker developed in our laboratory initially for C-terminal modified peptides, we have synthesized prostate specific antibody-poly-L-lysine (PLL) dendrimer conjugates by employing flourenylmethoxycarbonyl (Fmoc) Solid Phase Synthesis (SPS) protocol. We have successfully synthesized PSA peptide (HSSKLQL) and growing low generation Poly-L-Lysine (PLL) dendrimers; G1 and G2 respectively. The synthetic process involves activation of the linker with isoamyl nitrite and nucleophilic cleavage. We hope this approach will pave way for the synthesis of important macromolecules for biological applications.

並列關鍵字

Dendrimers ； Self-Assembly ； Prostate Specific Antibody

參考文獻

1. Sampathkumar, S.-G.; Yarema, K. J., Dendrimers in Cancer Treatment and Diagnosis. In Nanotechnologies for the Life Sciences, Wiley-VCH Verlag GmbH & Co. KGaA: 2007.

2. Abbasi, E.; Aval, S. F.; Akbarzadeh, A.; Milani, M.; Nasrabadi, H. T.; Joo, S. W.; Hanifehpour, Y.; Nejati-Koshki, K.; Pashaei-Asl, R., Dendrimers: synthesis, applications, and properties. Nanoscale Research Letters 2014, 9 (1), 247-247.

3. Tomalia, D. A.; Fréchet, J. M. J., Discovery of dendrimers and dendritic polymers: A brief historical perspective*. Journal of Polymer Science Part A: Polymer Chemistry 2002, 40 (16), 2719-2728.

4. Bosman, A. W.; Janssen, H. M.; Meijer, E. W., About Dendrimers:  Structure, Physical Properties, and Applications. Chemical Reviews 1999, 99 (7), 1665-1688.

5. Gillies, E. R.; Fréchet, J. M. J., Dendrimers and dendritic polymers in drug delivery. Drug Discovery Today 2005, 10 (1), 35-43.