Effects of Disulphide Bond Substitution with 1,2,3-Triazoles on the Biological Activity and Wound Repair Function of Amphibian-Derived Cathelicidins

文献类型： 外文期刊

第一作者： Guo, Kai

作者： Guo, Kai;Dong, Yuxiang;Ji, Shengli;Guo, Xuan

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关键词： Disulphide bond replacement with 1,2,3-Triazoles; Functional cosmetic cyclopeptide repair; Cathelicidins; Tag-assisted liquid-phase peptide synthesis; Click reaction; Cell proliferation

期刊名称：INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS （ 影响因子：2.4； 五年影响因子：2.0 ）

ISSN： 1573-3149

年卷期： 2025 年 31 卷 2 期

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收录情况： SCI

摘要： PurposeTo investigate the synthesis of artificial peptides and examine how modifying natural peptides with triazoles affects their biological activity. Focusing on two amphibian-derived peptides, Cathelicidin-NV and Cathelicidin-DM, which contain disulphide bonds, we explored how replacing these bonds with Triazoles could enhance stability and other biological functions.MethodsWe modified cathelicidin-NV and cathelicidin-DM with 1,2,3-Triazole to capitalise on its benefits. The effects of these Triazole-substituted disulphide bonds on the peptides' biological activities were systematically assessed.ResultsThe tag-assisted liquid-phase peptide synthesis method doubled the standard yield and reduced the consumption of 9-fluorenylmethyloxycarbonyl-amino acids by half. The modified peptides showed enhanced antimicrobial efficacy, with minimum inhibitory concentrations halved and bacteriostatic zone diameters nearly doubled compared to their natural counterparts. Additionally, these peptides demonstrated low cytotoxicity, high biocompatibility with mammalian cells, and improved stability, indicated by 6 and 11% higher retention rates after 24 and 48 h of incubation, respectively. The modifications also increased hydrogen bond formation and affinity between the peptides and protein kinases. Notably, the modifications of cathelicidin-NV and cathelicidin-DM enhanced the proliferation rates of HaCaT cells and HUVECs (from 10.3 and 5.7% to 14.6 and 13.6%, respectively) and improved the migration rates (from 6.7 and 0.7% to 2.9 and 5.3%, respectively).ConclusionThis study highlights the innovative design and optimisation of functional peptides through the incorporation of 1,2,3-Triazole, offering significant potential for advancing antimicrobial therapies and regenerative medicine.

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