Identification and functional characterisation of Esculentin-2 HYba peptides and their C-terminally amidated analogs from the skin secretion of an endemic frog.

Here, we report the identification, functional characterisation, and the effect of C-terminal amidation on the activity profile of two novel Esculentin-2 peptides (Esculentin-2 HYba1 and Esculentin-2 HYba2). The parent peptides and their analogs exhibited potent activity against the tested Gram-positive and Gram-negative bacteria. The effect of amidation was evident in the activity profile of fish pathogens and killing kinetics. The analogs showed a 10-fold decrease in MIC, and the killing time was reduced to 10-15 minutes. The hemolytic potential was unaltered upon amidation. The selectivity index revealed that these peptides are more selective to bacteria than mammalian cells. Cytotoxicity against Hep3B cells reveals their potential to destroy cancer cells; they showed potential inhibition compared to anticancer drug silymarin. The study also highlights the need for further truncations and modifications of esculentin peptides for developing them as lead drug molecules.