The College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, P. R. China.
J Med Chem. 2024 Jul 11;67(13):10891-10905. doi: 10.1021/acs.jmedchem.4c00394. Epub 2024 Jun 27.
Antifungal peptides are an appealing alternative to standard antifungal medicines due to their unique mechanism of action and low-level resistance. However, their susceptibility to protease degradation keeps hindering their future development. Herein, a library was established to design peptides with protease resistance and high antifungal activity. The peptides were incorporated with minimal D-amino acids to further improve the protease stability. The most active peptide, IR3, demonstrated good antifungal activity and low toxicity, and its molecular integrity was maintained after protease hydrolysis for 8 h at 2 mg/mL. Furthermore, IR3 could permeate the fungal cell wall, disrupt the cell membrane, produce reactive oxygen species, and induce apoptosis in fungal cells. experiments confirmed that IR3 could effectively treat fungal keratitis. Collectively, these findings suggest that IR3 is a promising antifungal agent and may be beneficial in the design and development of protease-resistant antifungal peptides.
抗菌肽由于其独特的作用机制和低水平的耐药性，成为了替代标准抗真菌药物的一种有吸引力的选择。然而，它们对蛋白酶降解的敏感性一直阻碍着它们的未来发展。在此，建立了一个文库来设计具有抗蛋白酶和高抗真菌活性的肽。这些肽中加入了最小量的 D-氨基酸，以进一步提高蛋白酶稳定性。最活跃的肽 IR3 表现出良好的抗真菌活性和低毒性，并且其分子完整性在 2mg/mL 下经过 8 小时蛋白酶水解后得以保持。此外，IR3 可以穿透真菌细胞壁，破坏细胞膜，产生活性氧物质，并诱导真菌细胞凋亡。实验证实，IR3 可以有效治疗真菌性角膜炎。综上所述，这些发现表明 IR3 是一种很有前途的抗真菌剂，可能有助于设计和开发抗蛋白酶的抗真菌肽。
