Truncated analog Brevinin2-CE-N26V5K: Revelation the Augmentation of Antimicrobial Activity.

Brevinin2-CE (B2CE), a natural peptide containing 37 amino acids, was first isolated from the skin secretions of the Chinese forest frog Rana chensinensis. B2CE shows good antibacterial activity. In this study, a series of B2CE analogs with differences in cationicity, α-helicity, hydrophobicity and amphipathic properties were designed through chain-length deletion and amino acid substitution. The most potent, nontoxic analog, B2CE-N26V5K, was identified by examination of its antibacterial activity, hemolytic activity, and stability under physiological conditions. The increased cationicity, hydrophobicity and more obvious hydrophilic and hydrophobic surface of B2CE-N26-N16WA18KG23K did not improve the antibacterial activity but increased the hemolytic activity of this modified peptide. The helicity might promote antibacterial activity for brevinin-2 peptides, as the 15-aa analogs with lower helicity show decreased potency against different test bacteria (approximately 2- to 72-fold) compared to B2CE-N26V5K. Additionally, the results indicated that the "Rana box" does not affect the antimicrobial activity of brevinin-2 peptides, as B2CE, B2CE-nonDS and B2CE-C31-37 S have similar strong inhibitory effects on both gram-positive and gram-negative bacteria. However, the "Rana box" does affect the hemolytic activity, as the HC