Ixosin-B是硬壁蝨唾液腺中具有抗菌活性的胜?。本研究以Ixosin-B為前導胜?，藉由固相胜?合成法合成一系列長度從8到12個胺基酸的短序列胜?(TSG-6、TSG-7、TSG-8、TSG-8-1、TSG-9 、TSG-9-1、TSG-10及TSG-11)以期了解Ixosin-B中不同序列的抗菌模式，並藉此設計出更具抗菌活性的胜?。這些胜?在抗菌實驗中對金黃色葡萄球菌及大腸桿菌的最小抑制濃度約8~64μM之間。由原二色光譜中發現這一系列的胜?二級結構螺旋結構並不明顯，這表示螺旋結構應不影響抗菌能力，另外，在這一系列的藥物較偏向毒殺大腸桿菌，因此推測可能是電荷聚集機制所造成影響。這些胜?中比較特別的是TSG-8-1，此胜?對金黃色葡萄球菌的抑制能力大於大腸桿菌，其最小抑制濃度分別為8μM及16μM。因此本研究亦利用E-coli ML-35p來探討新的抗菌原因，藉由內外膜穿透能力實驗發現它可使細菌外膜產生破裂造成物質流露。對於TSG-8-1比起其它胜?具有較好抗菌能力，從結構上顯示在胜?的一端若含有較多疏水性的區域有利於其進入細菌膜。在血溶性測試實驗中結果顯示，這一系列的抗菌胜?不會具有溶血的副作用。此外，我們也嘗試將TSG-8-1作用於癌細胞上，在毒殺癌細胞初步測試中發現TSG-8-1具有些許抗癌能力。 Ixosin-B is an antimicrobial peptide isolated from hard tick salivary glands. In this study, we took Ixosin-B as a lead peptide, designed and synthesized shorter peptide fragments of 8 to 12 amino acids by solid phase peptide synthesis, hoping to gain more understandings in the relationship between peptide structures and their antimicrobial activity. The minimum inhibitory concentration (MIC) of these peptides ranged from 8 to 64μM for Staphylococcus aureus and Escherichia coli, and higher activity for Escherichia coli was observed for majority of the peptides. Since helical structures were not prominent as evidenced in CD spectra, suggesting α-helix was not the main cause of bacterial death and the antibacterial activity may have been attributed to “Charge Cluster Mechanism”. TSG-8-1 on the other hand showed a completely different trend: the antibacterial activity for Staphylococcus aureus is higher than that for Escherichia coli. Mechanistic studies suggested that TSG-8-1, rich in hydrophobic amino acid residues, played important role in rupturing bacterial outer membrane. The same effect was not observed for bacterial inner membrane, and thus accounted for the preference in its killing of Gram positive bacteria. All peptides synthesized exhibited no hemolytic side effect. TSG-8-1 was also tested against breast cancer cell line (MCF-7) and slight cytotoxicity was observed.
