Bolosov Ilia A, Finkina Ekaterina I, Bogdanov Ivan V, Safronova Victoria N, Panteleev Pavel V, Ovchinnikova Tatiana V
M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Moscow Center for Advanced Studies, 123592 Moscow, Russia.
Pharmaceutics. 2024 Dec 17;16(12):1606. doi: 10.3390/pharmaceutics16121606.
: Antimicrobial peptides are generally considered promising drug candidates for combating resistant bacterial infections. However, the selectivity of their action may vary significantly. Natural gomesin, isolated from haemocytes of the tarantula , demonstrates a broad spectrum of antimicrobial activities, being the most effective against pathogenic fungi. : Here, we searched for variants of natural gomesin-like peptides and produced their recombinant analogs in the bacterial expression system. The antimicrobial activities of the obtained peptides were tested against a panel of bacterial and yeast strains, and their toxicity towards human cells was examined. : Most of the new analogs of gomesin have primary structures homologous to that of the natural gomesin; however, they have fewer amino acid residues and post-translational modifications. One of the discovered analogs, the His-rich shorter peptide from the spider , designated as DsGom, displays antifungal activity comparable with that of natural gomesin. In the process of the structural-functional study of DsGom, it was shown that this analog retains a basic mechanism of action similar to that of natural gomesin. The DsGom analog has a significantly better toxicity profile as compared to gomesin. At the same time, the loss of the first Arg residue reduces, but does not annul, the antifungal activity of DsGom. Moreover, the acidification of the growth medium reduces the loss of the antifungal activity of this analog. : The discovered natural gomesin-like peptides display more selective antifungal activities as compared to gomesin. The low cytotoxicity of DsGom, combined with its high antifungal activity and stability, allows us to consider it a promising drug candidate for the treatment of fungal infections, especially those caused by fungi of the Candida genus.
抗菌肽通常被认为是对抗耐药细菌感染的有前景的候选药物。然而，它们作用的选择性可能有很大差异。从狼蛛血细胞中分离出的天然戈麦辛具有广泛的抗菌活性，对致病真菌最为有效。
在这里，我们寻找天然戈麦辛样肽的变体，并在细菌表达系统中生产它们的重组类似物。测试了所得肽对一组细菌和酵母菌株的抗菌活性，并检测了它们对人类细胞的毒性。
大多数新的戈麦辛类似物的一级结构与天然戈麦辛同源；然而，它们的氨基酸残基和翻译后修饰较少。发现的一种类似物，即来自蜘蛛的富含组氨酸的较短肽，命名为DsGom，其抗真菌活性与天然戈麦辛相当。在对DsGom的结构功能研究过程中，表明该类似物保留了与天然戈麦辛相似的基本作用机制。与戈麦辛相比，DsGom类似物的毒性特征明显更好。同时，第一个精氨酸残基的缺失降低但并未消除DsGom的抗真菌活性。此外，生长培养基酸化减少了该类似物抗真菌活性的损失。
与戈麦辛相比，发现的天然戈麦辛样肽表现出更具选择性的抗真菌活性。DsGom的低细胞毒性，结合其高抗真菌活性和稳定性，使我们能够将其视为治疗真菌感染，特别是由念珠菌属真菌引起的感染的有前景的候选药物。
