Department of Polymer Science and Engineering, Sunchon National University, Suncheon, Jeonnam 57922, Korea.
Division of Applied Life Sciences and Research Institute of Natural Science, Gyeongsang National University, Jinju, Gyeongnam 52828, Korea.
Int J Mol Sci. 2018 Nov 28;19(12):3781. doi: 10.3390/ijms19123781.
Increases in the numbers of immunocompromised patients and the emergence of drug-resistance fungal pathogens have led to the need for new, safe, efficacious antifungal agents. In this study, we designed a histidine-lysine-lysine (HKK) motif and synthesized six HKK peptides with repetitions of the motif. These peptides showed length-dependent antifungal activity against drug-susceptible and drug-resistant fungal pathogens via membranolytic or non-membranolytic action. None of the peptides were cytotoxic to rat erythrocytes or NIH3T3 mouse embryonic fibroblasts. Short-length peptides were directly translocated in fungal cytosol and reacted with mitochondria, resulting in apoptosis. Membrane-permeabilizing activity occurred in the presence of long peptides, and peptides were able to transfer to the cytosol and induce reactive oxygen species. Our results suggest that peptides composed only of cationic amino acids may be good candidates as antifungal agents.
免疫功能低下患者数量的增加和耐药真菌病原体的出现，导致了对新型、安全、有效的抗真菌药物的需求。在这项研究中，我们设计了一个组氨酸-赖氨酸-赖氨酸（HKK）基序，并合成了六个具有该基序重复的 HKK 肽。这些肽通过膜溶解或非膜溶解作用，表现出对药敏和耐药真菌病原体的长度依赖性抗真菌活性。这些肽对大鼠红细胞或 NIH3T3 小鼠胚胎成纤维细胞均无细胞毒性。短肽可直接转位到真菌细胞质中，并与线粒体反应，导致细胞凋亡。在长肽存在的情况下，会发生膜通透性活性，肽能够转移到细胞质中并诱导活性氧。我们的研究结果表明，仅由阳离子氨基酸组成的肽可能是很好的抗真菌药物候选物。
