Department of Life and Environmental Physics, Horia Hulubei National Institute for Physics and Nuclear Engineering, Reactorului 30, PO Box MG-6, Măgurele 077125, Romania.
Molecular and Biomolecular Physics Department, National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath Street, 400293 Cluj-Napoca, Romania.
Biochim Biophys Acta Gen Subj. 2017 Jul;1861(7):1844-1854. doi: 10.1016/j.bbagen.2017.03.024. Epub 2017 Apr 2.
High antimicrobial efficacy of short tryptophan-and arginine-rich peptides makes them good candidates in the fight against pathogens. Substitution of tryptophan and arginine by histidine could be used to modulate the peptides efficacy by optimizing their structures.
The peptide (RRWWRWWRR), reported to showed good antimicrobial efficacy, was used as template, seven new analogs being designed substituting tryptophan or arginine with histidine. The peptides' efficacy was tested against E. coli, B. subtilis and S. aureus. The cytotoxicity and hemolytic effect were evaluated and the therapeutic index was inferred for each peptide. Atomic force microscopy and molecular simulation were used to analyze the effects of peptides on bacterial membrane.
The substitution of tryptophan by histidine proved to strongly modulate the antimicrobial activity, mainly by changing the peptide-to-membrane binding energy. The substitution of arginine has low effect on the antimicrobial efficacy. The presence of histidine residue reduced the cytotoxic and hemolytic activity of the peptides in some cases maintaining the same efficacy against bacteria. The peptides' antimicrobial activity was correlated to the 3D-hydrophobic moment and to a simple structure-based packing parameter.
The results show that some of these peptides have the potential to become good candidates to fight against bacteria. The substitution by histidine proved to fine tune the therapeutic index allowing the optimization of the peptide structure mainly by changing its binding energy and 3D-hydrophobic moment.
The short tryptophan reach peptides therapeutic index can be maximized using the histidine substitution to optimize their structure.
短色氨酸和精氨酸丰富肽具有很高的抗菌功效，使其成为对抗病原体的良好候选物。通过用组氨酸取代色氨酸和精氨酸，可以优化肽的结构，从而调节其功效。
使用（RRWWRWWRR）肽作为模板，设计了七个新的类似物，将色氨酸或精氨酸替换为组氨酸。测试了这些肽对大肠杆菌、枯草芽孢杆菌和金黄色葡萄球菌的抗菌效果。评估了细胞毒性和溶血作用，并推断了每种肽的治疗指数。原子力显微镜和分子模拟用于分析肽对细菌膜的影响。
用组氨酸取代色氨酸被证明可以强烈调节抗菌活性，主要是通过改变肽与膜的结合能。用组氨酸取代精氨酸对抗菌功效的影响较小。在某些情况下，组氨酸残基的存在降低了肽的细胞毒性和溶血活性，同时保持了对细菌的相同功效。肽的抗菌活性与 3D-疏水性矩和简单的基于结构的堆积参数相关。
结果表明，这些肽中的一些具有成为对抗细菌的良好候选物的潜力。用组氨酸取代被证明可以微调治疗指数，允许通过改变其结合能和 3D-疏水性矩来优化肽的结构。
使用组氨酸取代可以最大化短色氨酸到达肽的治疗指数，从而优化其结构。
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