Laboratory of Toxinology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasilia, Brasilia 70.910-900, DF, Brazil.
Laboratory of Protein Chemistry and Biochemistry, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia 70.910-900, DF, Brazil.
Biomolecules. 2023 Mar 22;13(3):576. doi: 10.3390/biom13030576.
The number of multidrug-resistant pathogenic microorganisms has been growing in recent years, most of which is due to the inappropriate use of the commercial antibiotics that are currently available. The dissemination of antimicrobial resistance represents a serious global public health problem. Thus, it is necessary to search for and develop new drugs that can act as antimicrobial agents. Antimicrobial peptides are a promising alternative for the development of new therapeutic drugs. Anurans' skin glands are a rich source of broad-spectrum antimicrobial compounds and hylids, a large and diverse family of tree frogs, are known as an important source of antimicrobial peptides. In the present study, two novel antimicrobial peptides, named Raniseptins-3 and -6, were isolated from skin secretion and their structural and biological properties were evaluated. Raniseptins-3 and -6 are cationic, rich in hydrophobic residues, and adopt an α-helix conformation in the presence of SDS (35 mM). Both peptides are active against Gram-negative bacteria and Gram-positive pathogens, with low hemolytic activity at therapeutic concentrations. No activity was observed for yeasts, but the peptides are highly cytotoxic against B16F10 murine melanoma cells and NIH3T3 mouse fibroblast cells. None of the tested compounds showed improvement trends in the MTT and LDH parameters of MHV-3 infected cells at the concentrations tested.
近年来，多药耐药性致病微生物的数量一直在增加，其中大部分是由于目前市售的商业抗生素使用不当所致。抗菌药物耐药性的传播是一个严重的全球公共卫生问题。因此，有必要寻找和开发新的可以作为抗菌药物的药物。抗菌肽是开发新治疗药物的有前途的替代品。蛙类皮肤腺体是广谱抗菌化合物的丰富来源，而树蛙科是树蛙的一个大而多样的家族，是抗菌肽的重要来源。在本研究中，从皮肤分泌物中分离出两种新型抗菌肽，命名为 Raniseptins-3 和 -6，并对其结构和生物学特性进行了评估。Raniseptins-3 和 -6 是阳离子的，富含疏水性残基，并在 SDS（35 mM）存在下采用 α-螺旋构象。这两种肽都对革兰氏阴性菌和革兰氏阳性病原体具有活性，在治疗浓度下对红细胞的溶血活性较低。对酵母没有活性，但肽对 B16F10 鼠黑色素瘤细胞和 NIH3T3 小鼠成纤维细胞具有高度细胞毒性。在测试的浓度下，测试的化合物均未显示出在 MHV-3 感染细胞的 MTT 和 LDH 参数方面有改善趋势。
