Role of positional hydrophobicity in the leishmanicidal activity of magainin 2
Role of positional hydrophobicity in the leishmanicidal activity of magainin 2
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DOI：
10.1128/aac.48.8.2980-2986.2004
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发表时间：
2004-08-01
影响因子：
4.9
通讯作者：
Rivas, L
中科院分区：
文献类型：
--
作者：
Guerrero, E;Saugar, JM;Rivas, L
膜活性抗菌肽的出现，作为新的替代品，对病原体的多重抗生素耐药性，需要设计更好的类似物。在线性抗菌肽的优化中所涉及的不同物理化学参数中，位置疏水性最近已被并入。这考虑了疏水残基在整个序列中的拓扑分布的概念，而不是疏水性作为肽的全局参数的经典概念，计算为残基的单个疏水性的总和。为了评估该参数对爪蟾抗菌肽2类似物的杀利什曼机制的贡献，测定了这些类似物中的两种，MG-H1（GIKKFLHIIWKFIKAFVGEIMNS）和MG-H2（IIKKFLHSIWKFGKAFVG EIMNI），其具有相似的电荷、氨基酸组成和疏水性，但位置疏水性不同，对杜氏利什曼原虫前鞭毛体的活性（T.塔奇河F.埃潘河M. Epand和K. Matsuzaki，Biochemistry 41：10723-10731，2002）。将活性与亲本肽FSW-爪蟾抗菌肽2（GIGKWLHSAKKFGKAFVGEIMNS）的活性进行比较。这三种肽在微摩尔浓度下具有活性，顺序为MG-H2 > MG-H1> F5 W-爪蟾抗菌肽2。这些活性不同于它们的溶血和杀菌活性。结果表明，位置的疏水性，这反映了存在的短延伸的序列富含疏水性氨基酸，起着重要的作用，杀利什曼肽的活动。
The emergence of membrane-active antimicrobial peptides as new alternatives against pathogens with multiantibiotic resistance requires the design of better analogues. Among the different physicochemical parameters involved in the optimization of linear antimicrobial peptides, positional hydrophobicity has recently been incorporated. This takes into consideration the concept of the topological distribution of hydrophobic residues throughout the sequence rather than the classical concept of hydrophobicity as a global parameter of the peptide, calculated as the summation of the individual hydrophobicities of the residues. In order to assess the contribution of this parameter to the leishmanicidal mechanisms of magainin 2 analogues, the activities of two of these analogues, MG-H1 (GIKKFLHIIWKFIKAFVGEIMNS) and MG-H2 (IIKKFLHSIWKFGKAFVG EIMNI), which have similar charges, amino acid compositions, and hydrophobicities but different positional hydrophobicities, against Leishmania donovani promastigotes were assayed (T. Tachi, R. F. Epand, R. M. Epand, and K. Matsuzaki, Biochemistry 41:10723-10731, 2002). The activities were compared with that of the parental peptide, FSW-magainin 2 (GIGKWLHSAKKFGKAFVGEIMNS). The three peptides were active at micromolar concentrations, in the order MG-H2 > MG-HI > F5W-magainin 2. These activities differ from their hemolytic and bactericidal activities. The results demonstrate that positional hydrophobicity, which reflects the presence of short stretches of sequences rich in hydrophobic amino acids, plays an important role in the activities of leishmanicidal peptides.