【摘要】：鴨抗菌肽Cathelicidin分子[Cath(1-20)]富含疏水性氨基酸及正電荷,通過人工方法設(shè)計(jì)合成Cath(1-20)的截短肽衍生物,篩選新型安全Cath(1-20)衍生肽,探討其作用機(jī)制。結(jié)果表明,與母肽Cath(1-20)相似,三種衍生肽Cath(5-20)、Cath(4-20)、Cath(3-20)均具有明顯廣譜抑菌活性,MIC值在1~8μmol·L~(-1)范圍內(nèi),但僅Cath(5-20)溶血及細(xì)胞毒性明顯降低,治療指數(shù)達(dá)19.5,顯著高于Cath(1-20)、Cath(4-20)及Cath(3-20)。Cath(1-20)及其衍生肽可破壞E.coli UB1005的內(nèi)膜完整性,產(chǎn)生去極化作用,并存在時(shí)間和劑量依賴效應(yīng);透射電鏡結(jié)果顯示Cath(1-20)及Cath(5-20)可破壞細(xì)菌細(xì)胞膜。研究證實(shí)氨基端的色氨酸對(duì)鴨抗菌肽Cath(1-20)溶血及細(xì)胞毒性起關(guān)鍵作用,其作用靶點(diǎn)主要為細(xì)菌細(xì)胞膜。
[Abstract]:Duck antimicrobial peptide Cathelicidin molecule [Cath (1-20)] is rich in hydrophobic amino acids and positive charges. The truncated peptide derivatives of Cath (1-20) were designed and synthesized by artificial method. The results showed that the three derivative peptides Cath (5-20), Cath (4-20), Cath (3-20) had broad spectrum antibacterial activity similar to the parent peptide Cath (1-20), and the MIC value was in the range of 1 渭 mol L ~ (-1). However, the hemolysis and cytotoxicity of Cath (5-20) were significantly decreased, and the therapeutic index was 19.5, which was significantly higher than that of Cath (1-20). Cath (4-20) and Cath (3-20). Cath (1-20) and their derived peptides could destroy the intimal integrity and depolarization of E.coli UB1005 in a time-and dose-dependent manner. Transmission electron microscopy showed that Cath (1-20) and Cath (5-20) could destroy bacterial cell membrane. It was confirmed that tryptophan at amino terminal plays a key role in hemolysis and cytotoxicity of duck antimicrobial peptide Cath _ (1-20), and its main target is bacterial cell membrane.
【作者單位】： 東北農(nóng)業(yè)大學(xué)動(dòng)物科學(xué)技術(shù)學(xué)院;
【基金】：黑龍江省自然科學(xué)基金(C2016022) 東北農(nóng)業(yè)大學(xué)“學(xué)術(shù)骨干”項(xiàng)目(15XG15)
【分類號(hào)】：S852.2
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本文編號(hào)：2338812