Systematic mutagenesis of oncocin reveals enhanced activity and insights into the mechanisms of antimicrobial activity†,Molecular Systems Design & Engineering

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Systematic mutagenesis of oncocin reveals enhanced activity and insights into the mechanisms of antimicrobial activity†
Molecular Systems Design & Engineering ( IF 3.2 ) Pub Date : 2018-10-08 00:00:00 , DOI: 10.1039/c8me00051d
Pin-Kuang Lai ₁ , Kathryn Geldart ₁ , Seth Ritter ₁ , Yiannis N Kaznessis ₁ , Benjamin J Hackel ₁

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Oncocin is a proline-rich antimicrobial peptide that inhibits protein synthesis by binding to the bacterial ribosome. In this work, the antimicrobial activity of oncocin was improved by systematic peptide mutagenesis and activity evaluation. We found that a pair of cationic substitutions (P4K and L7K/R) improves the activity by 2–4 fold (p < 0.05) against multiple Gram-negative bacteria. An in vitro transcription/translation assay indicated that the increased activity was not because of stronger ribosome binding. Rather a cellular internalization assay revealed a higher internalization rate for the optimized analogs thereby suggesting a mechanism to increase potency. In addition, we found that the optimized peptides' benefit is dependent upon nutrient-depleted media conditions. The molecular design and characterization strategies have broad potential for development of antimicrobial peptides.

中文翻译：

致癌素的系统诱变揭示了活性的增强和对抗菌活性机制的深入了解†

癌素是一种富含脯氨酸的抗菌肽，通过与细菌核糖体结合来抑制蛋白质合成。在这项工作中，通过系统的肽诱变和活性评估提高了致癌素的抗菌活性。我们发现一对阳离子取代（P4K 和 L7K/R）将针对多种革兰氏阴性细菌的活性提高了 2-4 倍（p < 0.05）。体外转录/翻译测定表明活性增加并不是因为核糖体结合更强。相反，细胞内化测定揭示了优化的类似物具有更高的内化率，从而表明了增加效力的机制。此外，我们发现优化的肽的益处取决于营养耗尽的培养基条件。分子设计和表征策略对于抗菌肽的开发具有广泛的潜力。

更新日期：2018-10-08

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