DESIGN OF MODEL AMPHIPATHIC PEPTIDES HAVING POTENT ANTIMICROBIAL ACTIVITIES
DESIGN OF MODEL AMPHIPATHIC PEPTIDES HAVING POTENT ANTIMICROBIAL ACTIVITIES
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DOI：
10.1021/bi00165a020
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发表时间：
1992-12-22
期刊：
影响因子：
2.9
通讯作者：
HOUGHTEN, RA
中科院分区：
文献类型：
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作者：
BLONDELLE, SE;HOUGHTEN, RA
诱导的两亲性α-螺旋构象在肽的生物活性中起重要作用。通过使用反相高效液相色谱（RP - HPLC）作为研究水/脂界面处肽的二级结构的手段，发现一个序列（Ac - LKLLKKLL - KKLKKLLKKL - NH₂）在RP - HPLC过程中与固定相的脂质基团相互作用时容易呈现两亲性α-螺旋构象。该肽对革兰氏阳性菌和革兰氏阴性菌均表现出强大的抗菌活性。我们制备了一套完整的缺失以及亮氨酸和赖氨酸取代的该序列的类似物。这些类似物被用于研究这些改变对母体序列的抗菌和溶血活性的影响，并与每个类似物在RP - HPLC过程中的行为相关联。还通过制备长度从8到22个残基不等但保持其两亲性的类似物，评估了这种两亲性模型肽在细胞膜上形成离子通道的潜力。
Induced amphipathic alpha-helical conformations play an important role in the biological activity of peptides, By using reversed-phase high-performance liquid chromatography (RP-HPLC) as a means to study the secondary structure of peptides at aqueous/lipid interfaces, a sequence (Ac-LKLLKKLL-KKLKKLLKKL-NH2) was found to readily adopt an amphipathic alpha-helical conformation upon interacting with the lipid groups of the stationary phase during RP-HPLC. This peptide exhibited potent antimicrobial activities against both Gram-positive and Gram-negative bacteria. We have prepared a complete set of omission, as well as of leucine and lysine substitution, analogs of this sequence. These analogs were used to investigate the effects of such alterations on the parent sequence's antimicrobial and hemolytic activities relative to each analog's behavior during RP-HPLC. The potential for the formation of ion channels through cell membranes by this amphipathic model peptide was also evaluated through preparation of analogs which varied in length from 8 to 22 residues, while maintaining their amphipathicity.