Molecular and Structural Biology Division, Central Drug Research Institute,CSIR, Lucknow 226001, India.
Biochemistry. 2010 Sep 14;49(36):7920-9. doi: 10.1021/bi100729m.
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 approximately 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.
蜂毒素是一种很好的抗菌肽模型，可用于了解其裂解细菌和哺乳动物细胞的基础。通过取代其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，设计了新型的蜂毒素类似物。还设计了一种具有与蜂毒素相同组成但亮氨酸拉链序列改变的乱序肽。尽管类似物具有相当的杀菌活性，但包括乱序肽在内的蜂毒素类似物的细胞毒性却大大降低。只有蜂毒素而不是它的类似物强烈定位于 hRBC 上，并形成约 2.2-3.4nm 的孔。然而，蜂毒素及其类似物在大肠杆菌上的定位相似，并在 Bacillus megaterium 上测试时形成不同大小的孔。这些数据表明，在蜂毒素亮氨酸拉链序列中用疏水性较小的丙氨酸残基取代疏水亮氨酸残基，仅在 hRBC 中而不是在测试的细菌中干扰其孔形成活性和机制。
