Antibacterial Activities of Short Designer Peptides: a Link between Propensity for Nanostructuring and Capacity for Membrane Destabilization

Antibacterial Activities of Short Designer Peptides: a Link between Propensity for Nanostructuring and Capacity for Membrane Destabilization
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短设计肽的抗菌活性:纳米结构倾向与膜不稳定能力之间的联系

DOI:
10.1021/bm901130u
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发表时间:
2010-02-01
期刊:
影响因子:
6.2
通讯作者:
Lu, Jian R.
Lu, Jian R.
中科院分区:
化学2区
文献类型:
--
作者:
Chen, Cuixia;Pan, Fang;Lu, Jian R.

文献摘要

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两亲性多肽A(3)K、A(6)K和A(9)K显示出随着疏水丙氨酸部分尺寸的增大而增加的纳米聚集倾向,聚集体的大小和形状显示出从A(3)K长纳米纤维由A(6)K形成的松散的多肽堆积到由A(9)K形成的短而窄的纳米棒的稳定过渡。这种尺寸和形状的转变与从界面堆积和曲率变化预测的趋势大体一致,如果将这些表面活性剂作为常规表面活性剂处理,则通过在给定的时间和多肽浓度下杀灭细菌的多肽百分率来定义抗菌能力。对A(9)K的显微和荧光成像研究表明,膜通透力和细菌聚集力随肽浓度和孵育时间的延长而增强。这些结果表明,尽管A(9)K暴露在预制的DPPC膜双层中,但其自组装倾向与膜穿透力和杀菌力之间存在正相关关系。对预制的DPPG膜双层进行相同的处理会导致模型膜结构的严重破坏,这一趋势与膜溶血研究中观察到的高选择性完全一致。
Amphiphilic peptides A(3)K, A(6)K and A(9)K displayed an increasing propensity for nanoaggregation with increasing the size of hydrophobic alanine moiety, and the size and shape of the aggregates showed a steady transition from loose peptide stacks formed by A(3)K long nanofibers by A(6)K, to short and narrow nanorods by A(9)K This size and shape transition was broadly consistent with the trend predicted from interfacial packing and curvature change if these peptide surfactants were treated as conventional surfactants The antibacterial capacity, defined by the killing of percentage of bacteria in a given time and peptide concentration, showed a strong correlation to peptide hydrophobicity, evident from both microscopic and fluorescence imaging studies For A(9)K, the power for membrane permeation and bacterial clustering intensified with peptide concentration and incubation time These results thus depict it positive correlation between the propensity for self-assembly of the peptides, their membrane penetration power, and bactericidal capacity Although the exposure of A(9)K to a preformed DPPC membrane bilayer showed little structural disturbance. the same treatment to the preformed DPPG membrane bilayer led to substantial disruption of model membrane structure, a trend entirely consistent with the high selectivity observed from membrane hemolytic studies.