Cell-Selective Lysis by Novel Analogues of Melittin against Human Red Blood Cells and Escherichia coli
Cell-Selective Lysis by Novel Analogues of Melittin against Human Red Blood Cells and Escherichia coli
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DOI：
10.1021/bi100729m
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发表时间：
2010-09-14
期刊：
影响因子：
2.9
通讯作者：
Ghosh, Jimut Kanti
中科院分区：
文献类型：
--
作者：
Pandey, Brijesh K.;Ahmad, Aqeel;Ghosh, Jimut Kanti
蜂毒肽是一个很好的模型抗菌肽，了解其对细菌和哺乳动物细胞的裂解活性的基础。通过取代先前鉴定的亮氨酸拉链基序的“d”和“a”位置处的亮氨酸残基，设计了蜂毒肽的新型类似物。还设计了具有与蜂毒肽相同的组成和改变的亮氨酸拉链序列的乱序肽。蜂毒肽的类似物，包括乱序肽显示细胞毒性急剧下降，虽然他们表现出相当的杀菌活性。只有蜂毒肽而不是其类似物强烈定位于hRBC上，并形成类似于2.2-3.4 nm的孔。然而，蜂毒肽及其类似物类似地定位于大肠杆菌上，并形成不同大小的孔，如在巨大芽孢杆菌上测试的。数据显示，蜂毒肽的亮氨酸拉链序列中疏水性亮氨酸残基被疏水性较小的丙氨酸残基取代仅在hRBC中而不是在测试的细菌中干扰其成孔活性和机制。
Melittin is a good model antimicrobial peptide to understand the basis of its lytic activities against bacteria and mammalian cells. Novel analogues of melittin were designed by substituting the leucine residue(s) at the "d" and "a" positions of its previously identified leucine zipper motif. A scrambled peptide having the same composition of melittin with altered leucine zipper sequence was also designed. The analogues of melittin including the scrambled peptide showed a drastic reduction in cytotoxicity though they exhibited comparable bactericidal activities. Only melittin but not its analogues localized strongly onto hRBCs and formed pores of similar to 2.2-3.4 nm. However, melittin and its analogues localized similarly onto Escherichia coli and formed pores of varying sizes as tested onto Bacillus megaterium. The data showed that the substitution of hydrophobic leucine residue(s) by lesser hydrophobic alanine residue(s) in the leucine zipper sequence of melittin disturbed its pore-forming activity and mechanism only in hRBCs but not in the tested bacteria.