Promotion of peptide antimicrobial activity by fatty acid conjugation
Promotion of peptide antimicrobial activity by fatty acid conjugation
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DOI：
10.1021/bc0341573
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发表时间：
2004-05-01
影响因子：
4.7
通讯作者：
Tirrell, MV
中科院分区：
文献类型：
--
作者：
Chu-Kung, AF;Bozzelli, KN;Tirrell, MV
将三种肽YGAA[KKAKAKAA]（2）（AKK）、KLFKRHLKWKII（SC 4）和YG[AKAKAKA]（2）（KAK）与月桂酸结合，并测试其对结构、抗菌活性和真核细胞毒性的影响。相对于未缀合的肽，缀合的AKK和SC 4肽显示出增加的抗微生物活性，但缀合的KAK肽没有。AKK的圆二色光谱显示出显着更大的增加，在其α-螺旋含量的共轭形式比肽KAK在含有磷脂酰乙醇胺/磷脂酰甘油囊泡，它模仿细菌膜的溶液。KAK和AKK肽及其相应的脂肪酸缀合物在磷脂酰胆碱囊泡（其模拟真核细胞的细胞膜）的存在下，其结构几乎没有变化。KAK和AKK肽和缀合物的溶血活性低。然而，SC 4脂肪酸缀合物表现出溶血活性的大幅增加，并且在磷脂酰胆碱囊泡的存在下螺旋含量相应增加。这些结果支持抗微生物肽溶血和抗微生物活性与二级结构变化相关的模型，因为肽与脂质膜相互作用。脂肪酸缀合可以通过增强肽在与细菌膜相互作用时形成二级结构的能力来改善肽作为抗微生物剂的有用性。
Three peptides, YGAA[KKAAKAA](2) (AKK), KLFKRHLKWKII (SC4), and YG[AKAKAAKA](2) (KAK), were conjugated with lauric acid and tested for the effect on their structure, antibacterial activity, and eukaryotic cell toxicity. The conjugated AKK and SC4 peptides showed increased antimicrobial activity relative to unconjugated peptides, but the conjugated KAK peptide did not. The circular dichroism spectrum of AKK showed a significantly larger increase in its a-helical content in the conjugated form than peptide KAK in a solution containing phosphatidylethanolamine/phosphotidylglycerol vesicles, which mimics bacterial membranes. The KAK and AKK peptides and their corresponding fatty acid conjugates showed little change in their structure in the presence of phosphatidylcholine vesicles, which mimic the cell membrane of eukaryotic cells. The hemolytic activity of the KAK and AKK peptides and conjugates was low. However, the SC4 fatty acid conjugate showed a large increase in hemolytic activity and a corresponding increase in helical content in the presence of phosphatidylcholine vesicles. These results support the model of antimicrobial peptide hemolytic and antimicrobial activity being linked to changes in secondary structure as the peptides interact with lipid membranes. Fatty acid conjugation may improve the usefulness of peptides as antimicrobial agents by enhancing their ability to form secondary structures upon interacting with the bacterial membranes.