Synthesis and Antimicrobial Activity of a New Drug Based on Retro-Analog Cathelicidin-Polypeptide SE-33
Through chemical synthesis the polypeptide SE-33, that is retro analogue of the natural antimicrobial protein cathelicidin LL-37, was synthesized. Like a natural peptide, polypeptide SE-33 forms an amphipathic alpha helix, but has an inverted amino acid sequence compared with cathelicidin. It was found the proximity of polypeptide SE-33 to the natural compound in physicochemical properties. In vitro experiments showed that polypeptide SE-33 possess the bactericidal action against the cells of Staphylococcus aureus Wood 46, comparable with the action of cathelicidin LL-37, as well as pronounced antifungal activity against clinical isolates of Candida albicans, Cryptococcus neoformans, Rhodotorula mucilaginosa, Trichosporon cutaneum, Geotrichum sp. The MICs of polypeptide SE-33 for different fungal strains were in the range of 31.2 to 1024 μg/mL. Polypeptide SE-33 demonstrated high activity in vivo in the model of vulvovaginal candidiasis (VVC) in mice, comparable to that of pimafucin. In the absence of side effects and signs of pathology, polypeptide SE-33 in all the doses tested (1, 10 and 50 mg/mL) statistically reduced the vaginal load of the mice in comparison to the placebo group. The pronounced antibacterial and antifungal activity of polypeptide SE-33, as well as the absence of a toxic effect in the VVC model in mice, allow us to consider polypeptide SE-33 as a promising antimicrobial agent.