Rational design of anti-microbial peptides with enhanced activity and low cytotoxicity based on the structure of the arginine/histidine-rich peptide, chensinin-1
Rational design of anti-microbial peptides with enhanced activity and low cytotoxicity based on the structure of the arginine/histidine-rich peptide, chensinin-1
复制标题
基于富含精氨酸/组氨酸的肽 chensinin-1 的结构合理设计具有增强活性和低细胞毒性的抗菌肽
DOI：
10.1111/j.1365-2672.2012.05355.x
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发表时间：
2012-09-01
影响因子：
4
通讯作者：
Wang, X.
中科院分区：
文献类型：
--
作者：
Shang, D.;Sun, Y.;Wang, X.
目的了解具有特殊结构的抗菌肽chensinin-1的构效关系，开发新型抗菌肽作为治疗药物。方法与结果设计并合成了一系列chensinin-1类似物，方法是在chensin1亲水面用亮氨酸取代1-3个甘氨酸或重排ITS序列中的部分残基。圆二色谱表明，类似物在50%三氟乙醇/水中为a螺旋构象，而在30 mmoL L-1十二烷基硫酸钠中为β链构象。多肽对革兰氏阳性细菌的抗菌活性增加了5-30倍，这些增加与多肽疏水性的增加是平行的。它们的溶血活性也有所增加。两亲性对Chensinin-1的杀菌活性影响不大。3种多肽均可导致负电荷脂质体中钙黄绿素的渗漏，但效果不同。这些多肽不会导致钙黄绿素从不带电荷的脂质体中泄漏。结论采用非周期结构的多肽可以通过增加多肽的疏水性来提高抗菌效果。其靶标是细菌的质膜。研究的意义和影响Chensinin-1可以作为一种新的前导分子用于研究具有非典型结构的AMPs。
Aims To understand the structureactivity relationship of chensinin-1, a anti-microbial peptide (AMP) with an unusual structure, and to develop novel AMPs as therapeutic agents. Methods and Results 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 a-helical-type conformations in 50% trifluoroethanol/water but adopted beta-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. Conclusions Peptide adopted an aperiodic structure can improve the anti-microbial potency by increasing peptide hydrophobicity. Its target is bacteria plasma membrane. Significance and Impact of the Study Chensinin-1 can act as a new lead molecule for the study of AMPs with atypical structures.