Study on the Structure-Activity Relationship of an Antimicrobial Peptide, Brevinin-2GUb, from the Skin Secretion of .

Antimicrobial peptides (AMPs) are considered potential alternatives to antibiotics due to their advantages in solving antibiotic resistance. Brevinin-2GUb, which was extracted from the skin secretion of , is a peptide with modest antimicrobial activity. Several analogues were designed to explore the structure-activity relationship and enhance its activity. In general, the Rana box is not an indispensable motif for the bioactivity of Brevinin-2GUb, and the first to the 19th amino acids at the N-terminal end are active fragments, such that shortening the peptide while maintaining its bioactivity is a promising strategy for the optimisation of peptides. Keeping a complete hydrophobic face and increasing the net charges are key factors for antimicrobial activity. With the increase of cationic charges, α-helical proportion, and amphipathicity, the activity of t-Brevinin-2GUb-6K (tB2U-6K), in combatting bacteria, drastically improved, especially against Gram-negative bacteria, and the peptide attained the capacity to kill clinical isolates and fungi as well, which made it possible to address some aspects of antibiotic resistance. Thus, peptide tB2U-6K, with potent antimicrobial activity against antibiotic-resistant bacteria, the capacity to inhibit the growth of biofilm, and low toxicity against normal cells, is of value to be further developed into an antimicrobial agent.