GENERATION OF ANALOGS HAVING POTENT ANTIMICROBIAL AND HEMOLYTIC ACTIVITIES WITH MINIMAL CHANGES FROM AN INACTIVE 16-RESIDUE PEPTIDE CORRESPONDING TO THE HELICAL REGION OF STAPHYLOCOCCUS-AUREUS DELTA-TOXIN
GENERATION OF ANALOGS HAVING POTENT ANTIMICROBIAL AND HEMOLYTIC ACTIVITIES WITH MINIMAL CHANGES FROM AN INACTIVE 16-RESIDUE PEPTIDE CORRESPONDING TO THE HELICAL REGION OF STAPHYLOCOCCUS-AUREUS DELTA-TOXIN
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DOI：
10.1093/protein/8.3.315
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发表时间：
1995-03-01
期刊：
影响因子：
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通讯作者：
NAGARAJ, R
中科院分区：
文献类型：
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作者：
DHOPLE, VM;NAGARAJ, R
δ-毒素是一种来自金黄色葡萄球菌的26个残基的肽，其序列为甲酰基 - MAQDIISTIGDLVKWIIDTVNKFTKK。核磁共振研究表明，IISTIGDLVKWIIDTV片段在毒素中呈α-螺旋构象。一种对应于此片段的合成肽，尽管呈螺旋状，但没有表现出溶血活性。由于像D和K这样的带电残基可能调节细胞溶解活性，因此合成了16个残基肽的类似物，其中D被K系统性地替换。第一个D以及两个D都被K替换的类似物显示出强大的抗菌和溶血活性。第二个D被K替换的类似物活性相对较低。然而，所有的肽都显示出具有相似螺旋含量的α-螺旋结构。发现这些肽的活性与其使模型膜透化的能力直接相关。因此，通过对带电氨基酸进行最少的明智替换，应该有可能从肽毒素的短片段中产生细胞溶解肽。
The delta-toxin is a 26-residue peptide from Staphylococcus aureus with the sequence formyl-MAQDIISTIGDLVKWIIDTVNKFTKK. NMR studies indicate that the segment IISTIGDLVKWIIDTV occurs in an alpha-helical conformation in the toxin, A synthetic peptide corresponding to this segment, although helical, did not exhibit hemolytic activity. Since charged residues like D and K are likely to modulate cytolytic activity, analogs of the 16-residue peptide were synthesized where D was systematically replaced by K, Analogs in which the first D and both Ds were replaced by K showed potent antimicrobial and hemolytic activities. The analog in which the second D was replaced by K was relatively less active, However, all the peptides showed an a-helical structure with similar helical content. The activities of the peptides were found to correlate directly with their ability to permeabilize model membranes. Thus, by minimal judicious replacement of charged amino acids, it should be possible to generate cytolytic peptides from short segments of peptide toxins.