Faculty of Life Science, Liaoning Normal University, Dalian, China.
J Appl Microbiol. 2012 Sep;113(3):677-85. doi: 10.1111/j.1365-2672.2012.05355.x. Epub 2012 Jun 27.
To understand the structure-activity relationship of chensinin-1, a anti-microbial peptide (AMP) with an unusual structure, and to develop novel AMPs as therapeutic agents.
A series of chensinin-1 analogues were designed and synthesized by one to three replacement of glycines with leucines at the hydrophilic face of chensinin-1 or rearrangement of some of the residues in its sequence. Circular dichroism spectroscopy showed that the analogues adopted α-helical-type conformations in 50% trifluoroethanol/water but adopted β-strand-type conformations in 30 mmol l(-1) sodium dodecyl sulphate. The anti-microbial activities of the peptides against Gram-positive bacteria increased 5- to 30-fold, and these increases paralleled the increases in the peptides' hydrophobicities. Their haemolytic activities also increased. Amphipathicities had little influence on the bactericidal activity of chensinin-1. All peptides caused leakage of calcein entrapped in negatively charged liposomes although with different efficiencies. The peptides did not induce leakage of calcein from uncharged liposomes.
Peptide adopted an aperiodic structure can improve the anti-microbial potency by increasing peptide hydrophobicity. Its target is bacteria plasma membrane.
Chensinin-1 can act as a new lead molecule for the study of AMPs with atypical structures.
了解 chensinin-1 的结构-活性关系，chensinin-1 是一种具有异常结构的抗菌肽 (AMP)，并开发新型 AMP 作为治疗剂。
通过在 chensinin-1 的亲水面上用亮氨酸替换一个到三个甘氨酸，或重新排列其序列中的一些残基，设计并合成了一系列 chensinin-1 类似物。圆二色性光谱表明，类似物在 50%三氟乙醇/水中采用α-螺旋型构象，而在 30mmol/L 十二烷基硫酸钠中采用β-折叠型构象。肽对革兰氏阳性菌的抗菌活性增加了 5 到 30 倍，这些增加与肽的疏水性增加平行。它们的溶血活性也增加了。两亲性对 chensinin-1 的杀菌活性影响不大。所有肽都引起带负电荷的脂质体中钙黄绿素的泄漏，尽管效率不同。肽不会诱导不带电的脂质体中钙黄绿素的泄漏。
采用非周期性结构的肽可以通过增加肽的疏水性来提高抗菌效力。其靶标是细菌质膜。
Chensinin-1 可以作为研究具有非典型结构的 AMP 的新先导分子。
