合成五胜肽(KTTKS)之衍生物以發展功能性脂質體

• Main Authors: Hsieh Kai-Hsuan, 謝愷軒
• Other Authors: Cheng Chien-Chung
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/60842364584880746409

碩士 === 國立嘉義大學 === 應用化學系研究所 === 104 === Nowadays, cell-penetrating peptide is considered a popular research project, with its advantages like characteristics of penetrating cell membrane and good biocompatibility. However, many drugs have poorly water-soluble, so this experiment is desirable to combine hydrophobic drug and the hydrophilic cell-penetrating peptides to improve drug solubility and biocompatibility problem. After amphiphilic-derivative molecules are made, they can be made into liposomes not only can further enhance the ability to penetrate cells, but also can be used as drug carriers. In this study, we used the characteristics of solid-phase peptide synthesis, so that the purification process were quick and easy. In the experiment, we combined pentapeptide (KTTKS) with a variety of electrophilic group functional molecules, such as: rhodamine B (RhB), norcantharidin (NCTD), caffeic acid (CA) and stearic acid(18C), to make the formation of a functional amphiphilic molecules. On the other hand, in order to overcome the nucleophilic compounds can not be directly applied to the solid-phase peptide synthesis, we solved this problem with succinic anhydride to be a bridge between the reactants. We used liposomes of RhB-KTTKS and NCTD-KTTKS in biological drug experiments. The experimental results indicated that RhB-KTTKS monomeric state could penetrate into E. coli, and in the zebrafish experiments, the monomer and the liposomes in the kidney, gastrointestinal tract and ganglion hade fluorescence response, this indicated RhB-KTTKS could penetrate into the zebrafish. When NCTD-KTTKS using in zebrafish drug test, monomeric state was found invalid and liposomes state had significant effect. This indicated the formation of liposomes could enhance the cellular uptake. If we use the pentapeptides as a carrier in the future, to increase the solubility and biocompatibility; therefore we can bring hydrophobic drugs into a living body, and so that it can solve many problems of modern drugs.