组蛋白H2A衍生的抗菌肽parasin I的构效关系,Peptides

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组蛋白H2A衍生的抗菌肽parasin I的构效关系
Peptides Pub Date : 2008-07-01 , DOI: 10.1016/j.peptides.2008.02.019
Young Sook Koo , Jung Min Kim , In Yup Park , Byung Jo Yu , Su A Jang , Key-Sun Kim , Chan Bae Park , Ju Hyun Cho , Sun Chang Kim

研究了19氨基酸组蛋白H2A衍生的抗菌肽——parasin I的构效关系及其作用机理。在螺旋促进环境中，Parasin I形成了两亲性α螺旋结构（残基9-17），两侧是两个随机的螺旋区（残基1-8和18-19）。在N末端[Pa（2-19）]赖氨酸残基的删除导致抗菌活性的损失，但不影响该肽的α-螺旋含量。当赖氨酸残基被另一个碱性残基精氨酸（[R（1）] Pa）取代而不是极性，中性或酸性残基时，抗菌活性得以恢复。从C端[Pa（1-17），Pa（1-15）]进行性删除会稍微增加抗菌活性（1-4 microg / ml），而不会影响肽的α-螺旋含量。然而，进一步删除[Pa（1-14）]导致抗菌活性和α螺旋结构几乎完全丧失。共聚焦显微镜分析和膜透化测定表明，具有可比的抗微生物活性的parasin I及其类似物位于细胞膜上，并随后使外膜和细胞质膜透化。Pa（1-14）也定位于细胞膜，但失去了膜透化活性，而Pa（2-19）显示出较差的膜结合和透化活性。结果表明，在N-末端的碱性残基对于parasin I的膜结合活性是必不可少的，并且在膜结合parasin I类似物中，α-螺旋结构对于膜透化活性是必需的。

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Structure–activity relations of parasin I, a histone H2A-derived antimicrobial peptide

The structure-activity relations and mechanism of action of parasin I, a 19-amino acid histone H2A-derived antimicrobial peptide, were investigated. Parasin I formed an amphipathic alpha-helical structure (residues 9-17) flanked by two random coil regions (residues 1-8 and 18-19) in helix-promoting environments. Deletion of the lysine residue at the N-terminal [Pa(2-19)] resulted in loss of antimicrobial activity, but did not affect the alpha-helical content of the peptide. The antimicrobial activity was recovered when the lysine residue was substituted with another basic residue, arginine ([R(1)]Pa), but not with polar, neutral, or acidic residues. Progressive deletions from the C-terminal [Pa(1-17), Pa(1-15)] slightly increased the antimicrobial activity (1-4 microg/ml) without affecting the alpha-helical content of the peptide. However, further deletion [Pa(1-14)] resulted in nearly complete loss of antimicrobial activity and alpha-helical structure. Confocal microscopic analysis and membrane permeabilization assays showed that parasin I and its analogs with comparable antimicrobial activities localized to the cell membrane and subsequently permeabilized the outer and cytoplasmic membranes. Pa(1-14) also localized to the cell membrane, but lost membrane-permeabilizing activity, whereas Pa(2-19) showed poor membrane-binding and -permeabilizing activities. The results indicate that the basic residue at the N-terminal is essential for the membrane-binding activity of parasin I, and among the membrane-binding parasin I analogs, the alpha-helical structure is necessary for the membrane-permeabilizing activity.

更新日期：2008-07-01

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