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首页> 外文期刊>International journal of peptide research and therapeutics >Comparative In-Vitro Functional Analysis of Synthetic Defensins and Their Corresponding Peptide Variants Against HIV-1NL4.3, E. coli, S. aureus and P. aeruginosa
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Comparative In-Vitro Functional Analysis of Synthetic Defensins and Their Corresponding Peptide Variants Against HIV-1NL4.3, E. coli, S. aureus and P. aeruginosa

机译：合成防御素及其对应的针对HIV-1NL4.3，大肠杆菌，金黄色葡萄球菌和铜绿假单胞菌的肽变异体的体外功能分析

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Defensins found in mammals belong to mainly two subfamilies alpha- and beta-defensins. Mammalian defensins are small molecules (18-45 residues) that are cysteine, arginine rich compounds. Antimicrobial activities of these peptides were shown against a wide variety of microbes including bacteria, fungi, viruses and protozoan parasites. To investigate the structure and activity relationship, amino acid substitutions that alter charge were introduced into synthetic defensin peptides by adding 2-2 Arg (RR) and Asp (DD) at both the terminal and tested their effects on HIV-1, E. coli, S. aureus, and P. aeruginosa. In the present study, we have chemically synthesized native defensin peptides and their variants with Arg (RR) and Asp (DD) amino acid residues at N- and C-termini. Later, we assayed their anti-HIV, anti-microbial activities, stability, cytotox-icity and hemolytic properties. We reported that anti-HIV and antimicrobial activities of native defensins is increased significantly by adding Arg (RR) residues at both the termini while the substitution of Arg (RR) with Asp (DD), eliminate anti-HIV and antimicrobial activity against all bacterial species tested. While other physical features i.e. stability, cell toxicity and hemolytic property were not affected by any of the changes in the sequence. The results suggest that the terminal residues in defensins are crucial functional elements that determine their microbicidal potency. The enhanced microbicidal activity observed for defensin peptides with Arg (RR) residues could be due to optimization of amphiphilicity of the structure, which could facilitate specific interactions with the microbial membranes.
机译：在哺乳动物中发现的防御素主要属于α-防御素和β-防御素两个亚家族。哺乳动物防御素是小分子（18-45个残基），是富含半胱氨酸和精氨酸的化合物。这些肽对多种微生物的抗菌活性已显示，包括细菌，真菌，病毒和原生动物寄生虫。为了研究结构和活性之间的关系，通过在末端两个末端添加2-2 Arg（RR）和Asp（DD），将改变电荷的氨基酸取代引入合成防御素肽中，并测试它们对HIV-1，大肠杆菌的影响，金黄色葡萄球菌和铜绿假单胞菌。在本研究中，我们已经化学合成了天然防御素肽及其变异体，在N和C末端带有Arg（RR）和Asp（DD）氨基酸残基。后来，我们分析了它们的抗HIV，抗微生物活性，稳定性，细胞毒性和溶血特性。我们报告说，通过在两个末端均添加Arg（RR）残基，同时用Asp（DD）取代Arg（RR），消除了针对所有细菌的抗HIV和抗菌活性，天然防御素的抗HIV和抗菌活性大大提高了。经过测试的物种。而其他物理特征，即稳定性，细胞毒性和溶血特性不受序列中任何变化的影响。结果表明防御素中的末端残基是决定其杀菌力的关键功能元件。带有Arg（RR）残基的防御素肽所观察到的增强的杀微生物活性可能是由于结构两亲性的优化，可以促进与微生物膜的特异性相互作用。

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