Binase deletion mutant with enhanced cytotoxic properties

Kazan (Volga region) Federal University, Kazan, Kremlyovskaya St., 18, 420008, Russian Federation

^* Corresponding author: s_kosnyrev@mail.ru

Abstract

Antitumor peptides are a new class of small molecules characterized by high specificity and therapeutic efficacy. One of the strategies for developing peptide-based therapeutic agents is the modification of the physicochemical properties and structural characteristics of known peptides and cytotoxic proteins. Bacillus pumilus ribonuclease, binase, possesses antitumor activity. Using bioinformatics tools, we have developed a strategy for modifying of amino acid sequence of the antitumor binase peptide to enhance its cytotoxic properties. the binase peptide. A genetic construct enabling the peptide biosynthesis in recombinant strain was engineered. The peptide preparation was purified by metal chelate affinity chromatography. Cytotoxic properties of the purified peptide were assessed according to metabolic activity of tumor cells. Intracellular localization of the peptide was determined by means of fluorescence microscopy. In the study, we have genetically modified the binase peptide in order to change its physicochemical and structural properties. It made it possible to enhance its cytotoxic potential towards human lung adenocarcinoma line A549, but specificity was decreased. Thus, that modification of structural and physicochemical properties of therapeutic peptides is an important step in the development of antitumor drugs.