Beloborodov Evgenii, Iurova Elena, Sugak Dmitrii, Rastorgueva Eugenia, Pogodina Evgeniya, Fomin Aleksandr, Viktorov Denis, Slesarev Sergei, Saenko Yury
Laboratory of Research and Development of Peptide Drugs and Vaccines, S.P. Kapitsa Technological Research Institute, Ulyanovsk State University, Ulyanovsk, Russia.
Department of General and Clinical Pharmacology and Microbiology, Faculty of Medicine, Ulyanovsk State University, Ulyanovsk, Russia.
Curr Cancer Drug Targets. 2024;24(12):1275-1285. doi: 10.2174/0115680096285288240118090050.
Bombesin (BBN) is a short peptide with a high affinity for receptors that are expressed on the surface of various types of cancer cells. However, a full length BBN molecule has low stability.
In our study, we propose the use of peptide toxins, derived from animal and plant toxins, as scaffold molecules to enhance the bioavailability and stability of bombesin. These peptides possess a unique structure known as an inhibitory cystine knot.
We synthesized structures in which short bombesin was incorporated into various domains of arthropod and plant toxins using solid-phase peptide synthesis. The stability under different conditions was assessed through high-performance liquid chromatography, and binding to cell cultures expressing the bombesin receptor was analyzed. Additionally, toxicity to cell cultures was evaluated using fluorescence microscopy.
The data obtained demonstrated that placing the short peptide between the first and second cysteine residues in arachnid toxins results in increased stability and bioavailability, as well as low cytotoxicity.
Arachnid toxins with an inhibitory cystine knot can be considered as a scaffold for increasing the stability of therapeutic peptides.
蛙皮素（BBN）是一种短肽，对多种类型癌细胞表面表达的受体具有高亲和力。然而，全长BBN分子稳定性较低。
在我们的研究中，我们提议使用源自动物和植物毒素的肽毒素作为支架分子，以提高蛙皮素的生物利用度和稳定性。这些肽具有一种称为抑制性胱氨酸结的独特结构。
我们使用固相肽合成法合成了将短蛙皮素掺入节肢动物和植物毒素各个结构域的结构。通过高效液相色谱评估不同条件下的稳定性，并分析与表达蛙皮素受体的细胞培养物的结合。此外，使用荧光显微镜评估对细胞培养物的毒性。
获得的数据表明，将短肽置于蛛形纲动物毒素的第一个和第二个半胱氨酸残基之间会导致稳定性和生物利用度增加，以及低细胞毒性。
具有抑制性胱氨酸结的蛛形纲动物毒素可被视为提高治疗性肽稳定性的支架。
