Neurosteroids in Epilepsy
Selective Carbonic anhydrase IX inhibitors
Novel anti-inflammatory compounds
selective 17βHSD1 inhibitors
Wild bee venom peptides
Increasing resistance of microbial, yeast and fungal strains to antibiotic and antifungal treatment is dangerous trend of last decade. Decreasing efficiency of common treatments poses a serious health and economical problem worldwide. Recently, we have isolated and characterized remarkable antimicrobial peptides (AMPs) from the venom reservoirs of wild bees which mechanism of action promises robust solution preventing further development of resistance.
AMPs from bee venom and its synthetic analogues are cationic peptides containing circa 10 – 20 amino acids. Amphipathic nature of AMPs is standing behind disruption of bacterial and fungal membrane resulting in eradication of pathogens. AMPs were preliminary tested for cell toxicity (mammalian cell cultures), hemolysis and rabbit eye irritation test without significant negative results, which indicated suitability of AMPs to be used in human medicine, dermatology, beauty industry, intimate hygiene or surface disinfection. Moreover, a stability of synthetic AMPs analogues has been increased to prevent hydrolysis of peptides by peptidases present on site or produced by pathogens. Efficacy of AMPs has been tested in using bacterial, fungal and yeast strains including common antibiotics or fluconazole resistant strains such as Staphylococcus aureus or Candida species. Despite peptide nature of compounds limits per oral application of compound in human medicine, topic application or use of compounds in dermatology or intimate hygiene should be beneficial mainly because of treatment efficacy and decreased exposure of patients to common antibiotics
Antimicrobial activity represented by Minimum inhibitory concentration (MIC) has been studied for AMPs using various species of bacteria or yeast and compared with hemolytic activity of peptides. Several candidate AMPs were identified as compounds effective against broad range of pathogens while hemolytic activity has not been observed (see peptide A; Table 1). MIC values of peptides LL-III/2 and LL-III/A for different Candida species and for different number of cells in suspensions (A = circa 0.5-2.5×104 cells per mL) were measured. Peptides were found to be effective antifungal agent even for fluconazole resistant Candida strains (Table 2).
The project is offered for co-development and licensing.
Efficacy of various AMPs has been confirmed using various bacterial, fungal and yeast strains in vitro. Simultaneously, AMPs were tested for mammalian cell toxicity and hemolysis. Pilot experiments showed very low irritation using rabbit eye test. Testing of novel peptides and their analogues is under way aiming optimization of efficacy and stability. Tests of skin or mucous membranes irritation are planned.
AMPs from wild bee venom are protected by European patents EP 2265631 and EP 2396020. Newly isolated peptides and most promising synthetic analogues will be patented during spring 2014. This is opportunity for future industry partner to select areas of interest which should be covered by patent.
Institute of Organic Chemistry and Biochemistry AS CR, v.v.i.
Veterinary Research Institute v.v.i.
Palacký University Olomouc
Monincová L., Slaninová J., Fučík V., Hovorka O., Voburka Z., Bednárová L., Maloň P., Štokrová J., Čeřovský V.: Lasiocepsin, a novel cyclic antimicrobial peptide from the venom of eusocial bee Lasioglossum laticeps Hymenoptera: Halictidae). Amino Acids 43, 751-761, 2012.
Chapuis H., Slaninová J., Bednárová L., Monincová L., Buděšínský M., Čeřovský V.: Effect of hydrocarbon stapling on the properties of α-helical antimicrobial peptides isolated from the venom of Hymenoptera. Amino Acids 43, 2047-2058, 2012.
Slaninová J., Mlsová V., Kroupová H., Alán L., Tůmová T., Monincová L., Borovičková L., Fučík V., Čeřovský V.: Toxicity of new antimicrobial peptides from wild bee venom and their analogs towards mammalian normal and cancer cells. Peptides 33, 18-26, 2012.
Slaninová J., Putnová H., Borovičková L., Šácha P., Čeřovský V., Monincová L., Fučík V.: The antifungal effect of peptides from hymenoptera venom and their analogs. Central European Journal of Biology 6, 150-159, 2011