Alanine scanning analysis and structure-function relationships of the frog-skin antimicrobial peptide temporin-1Ta
Alanine scanning analysis and structure-function relationships of the frog-skin antimicrobial peptide temporin-1Ta
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DOI：
10.1002/psc.1350
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发表时间：
2011-05-01
影响因子：
2.1
通讯作者：
Mangoni, Maria Luisa
中科院分区：
文献类型：
--
作者：
Grieco, Paolo;Luca, Vincenzo;Mangoni, Maria Luisa
细菌和真菌对现有抗生素/抗真菌药物的耐药性不断增加，这促使人们寻找具有新作用模式的新抗感染化合物。因此，天然CAMP代表有前途和有吸引力的候选人。特别注意一直致力于蛙皮temporins，因为他们的短尺寸（10-14残基长）和他们的独特功能。特别地，temporin-1 Ta具有以下性质：（i）它主要对革兰氏阳性细菌有活性;（ii）当与temporin-1 Tl组合时，它可以协同抑制革兰氏阴性细菌生长和LPS的毒性作用;（iii）它在血清存在下保持生物活性;和（iv）它实际上不溶血。CAMPs的合理设计代表了获得具有更好治疗指数的肽的直接方法。在这里，我们使用丙氨酸扫描类似物来阐明每个氨基酸残基的侧链对肽的抗微生物和溶血活性的贡献。除了深入了解肽序列中的生物物理属性和关键位置（控制这种临时蛋白亚型的抗菌/溶血活性）之外，我们的研究还有助于优化基于临时蛋白的先导结构的设计，以生产新的抗感染药物。版权所有（C）2011欧洲肽协会和约翰威利父子有限公司。
The increasing resistance of bacteria and fungi to the available antibiotic/antimycotic drugs urges for a search for new anti-infective compounds with new modes of action. In line of this, natural CAMPs represent promising and attractive candidates. Special attention has been devoted to frog-skin temporins, because of their short size (10-14 residues long) and their unique features. In particular, temporin-1Ta has the following properties: (i) it is mainly active on Gram-positive bacteria; (ii) it can synergize, when combined with temporin-1Tl, in inhibiting both gram-negative bacterial growth and the toxic effect of LPS; (iii) it preserves biological activity in the presence of serum; and (iv) it is practically not hemolytic. Rational design of CAMPs represents a straightforward approach to obtain a peptide with a better therapeutic index. Here, we used alanine scanning analogs to elucidate the contribution of the side chains of each amino acid residue to the peptide's antimicrobial and hemolytic activity. Beside providing insight into the biophysical attributes and the critical positions within the peptide sequence, which govern the antimicrobial/hemolytic activity of this temporin isoform, our studies assist in optimizing the design of temporin-based lead structures for the production of new anti-infective agents. Copyright (C) 2011 European Peptide Society and John Wiley & Sons, Ltd.