近年來由於抗生素濫用，導致越來越多致病菌產生抗藥性，所以急迫需要開發新的替代藥物。抗微生物胜肽的抗菌機制不同於抗生素藥物，不需與受體結合即能發揮作用，因此較不易引起抗藥性，且具有廣效性、高效性、選擇性及穩定性，是極具潛力能替代抗生素成為更優良的抗菌藥物。本實驗室先前發表設計一系列從壁蝨唾液腺中分離的 Ixosin-B 之胜肽類似物，並自行合成、純化及測試生物活性，實驗結果顯示其中的 MAP-0403 胜肽具有最佳的抗菌活性，但溶血性較高。後又以此 (MAP-0403) 為模板胜肽而設計出 JJ 系列，由實驗結果可知，該系列中之 JJ-02 擁有最佳的抗菌活性，且具有低溶血性。因此本實驗以 JJ-02 作為胜肽設計模板，並採取不同策略設計出三段胜肽，分別為 SL-01、SL-02、SL-03，三者並稱為「SL 系列」，以期得到更強的抗菌活性及溶血性更低的抗微生物胜肽。本實驗利用固相胜肽合成法製備所需胜肽；逆相高效能液相層析儀進行純化；基質輔助雷射脫附游離飛行時間質譜儀進行鑑定分子量，最後得到高純度的目標胜肽，遂利用抗菌活性測試、抗癌活性測試及溶血活性測試進行活性分析。透過胺基酸置換策略及各胜肽之活性結果可知， Proline 兩端之胺基酸性質對胜肽序列具有一定的影響。總結而論，應是 SL-03 最具有後續研究價值，而SL-02可能顯示出其對革蘭氏菌的選擇性，亦可作為後續延伸探討的分支。 The widespread use of antibiotics and biocides and the development of tourism and trade contribute to the rapid spread of antimicrobial resistance (AMR) and multiple-drug resistance (MDR). Therefore, it is urgent to develop new antibacterial agents. The antibacterial mechanism of the antimicrobial peptides are different from that of antibiotics. They can work without binding the receptors. It is not only less susceptible to drug resistance, but also has broad-spectrum, high-efficiency, selectivity and stability. Therefore, AMPs are potential to become new antimicrobial agents because of their characteristics. The laboratory published a series of peptides of Ixosin-B isolated from the salivary glands of the tick. The Ixosin-B peptides were preparated and tested by ourselves. The experimental results showed that the MAP-0403 peptide had the best antibacterial activity, but the hemolytic activity was higher. The JJ series used the MAP-0403 as a template peptide. From the experimental results, JJ-02 in this series had the best antibacterial activity and low hemolysis. In this study, we used the JJ-02 as the parent peptide to design its analogs – SL series. All of them were synthesized by solid phase peptide synthesis (SPPS), purified by RP-HPLC, and characterized by MALDI-TOF MS. Their antimicrobial activities were analyzed by using the Micro broth dilution method. Their anticancer activities were analyzed by using the MTT assay. Their hemolytic activities were analyzed by using hemolytic assay. By the amino acid replacement strategy, the results showed that the amino acid properties at both ends of Proline have a certain influence on the peptide sequence. In summary, SL-02 and SL-03 were selected as our leading peptides for subsequent development of antibacterial agents.
