Abstract
Bombesin receptors on the cell surface are of great interest as a target for targeted cancer therapy. One of the strategies of targeting bombesin receptors involves the use of tropic short peptides. However, the main limitation for the wide application of peptides as drugs is their low stability in vivo due to their sensitivity to extreme conditions of the internal body environment such as temperature and action of enzymes. In our work, a short bombesin peptide, taken as a basis, was modified with a knottin, a toxin with an inhibitor cystine knot, increasing thereby the stability of the short peptide under various conditions. The aim of the investigation is to study the chemical and radiochemical stability of the structure based on the short bombesin peptide and knottin, as well as the ability of the obtained structure to bind to tumor cells. MATERIALS AND METHODS: The work analyzed the chemical and radiochemical stability of the synthesized peptide labeled with a lutetium radioisotope using high-performance liquid chromatography. A fluorescent-labeled peptide, obtained by a solid-phase peptide synthesis, was used to analyze binding to cultures expressing bombesin receptors. RESULTS: The analysis has shown increased chemical and radiochemical stability of the knottin-modified peptide, as compared to the commercial analog, and maintenance of a high ability to bind to receptors on the surface of cancer cells. CONCLUSION: The structure created on the basis of a short bombesin peptide and knottin possesses increased stability and retains the ability to bind to cancer cells. All this allows us to consider the creation of these structures as a strategy for fabricating stabilizing scaffolds for short peptides for a peptide-receptor therapy.