本論文設計與合成了兩系列含硼胜肽化合物。此兩類化合物可以以簡單的合成方法製備與純化。系列A：胜肽的起始物與胜肽化合物經偶和反應後生成硼酯胜肽化合物。硼酯胜肽化合物可利用KHF2水溶液將硼酯轉換成三氟硼酸化合物。三氟硼酸化合物可利用SiO2在EtOAc/H2O = 1:1之溶液中輕易地將三氟硼酸轉變成相對應的硼酸化合物；系列B：胜肽化合物與含三氟硼酸官能基的起始物在甲醇反應形成imine中間物後，加入PEMB以形成三氟硼酸基之類胜肽化合物。 在抑制MDA-MB231(乳癌細胞)以及HepG2(肝癌細胞)的實驗中，藉由改變胜肽化合物的結構與含硼官能基來觀察結構之改變與抑制MDA-MB231、HepG2的關係。實驗結果發現，系列A：化合物A-07、A-08、A-09、A-11、A-12對於HepG2癌細胞具有抑制的效果。有趣的是，增加胜肽結構之長度並不會對抗癌活性有所幫助，而是α位置上的取代基對於抑制效果具有重要的影響，另外，在硼官能基中則是以三氟硼酸的抑制效果最好。系列B：僅有部分三胜肽含硼化合物對於MDA-MB231、HepG2有抑制效果。其最佳結構條件為：第一號位置為Val，第二號位置必須為Phe，第三號位置須為Phe (B38)或者是Ser(Bzl) (B41)，而硼的官能基則是以三氟硼酸的表現較好。 In the thesis, we have designed and synthesized two series of boron-containing peptide analogues. These analogues were prepared via efficient and straightforward synthetic protocols. Biological evaluations of synthesized compounds were accomplished through zebra fish and MTT assays respectively. Structure-activity relationship (SAR) indicated that A-07, A-08, A-09, A-11 A-12 are potent against HepG2 (liver cancer) cells but not MDA-MB231 (drug resistant breast cancer) cells. B38, were found potent against HepG2 but not MDA-MB231. B41 being one of the most potent analogues of 2 series, was active against HepG2 and MDA-MB231 cell lines. In summary, inclusion of a phenylalanine at position 2, a benzyl-protected serine at position 3, and a potassium trifluoroborate greatly improved the potency of the molecule against either HepG2 or MDA-MB231 cell lines.
