Branched peptides with antibacterial and anti-inflammatory activity

Despite their broad-spectrum efficacy and immunomodulatory properties, antimicrobial peptides (AMPs) still face limitations due to poor proteolytic stability and reduced in vivo bioavailability. The proposed strategy involves the development of tetrameric AMPs, obtained using three lysine residues as a scaffold, which confer enhanced protease resistance compared to monomeric analogues, thereby prolonging their circulating half-life while maintaining low cytotoxicity toward eukaryotic cells. The peptides have demonstrated stability and efficacy in topical formulations as well as systemic activity in a murine infection model.

The physicochemical properties of these AMPs confer strong antibiofilm activity (matrix disaggregation), making them particularly relevant for the prevention and treatment of infections associated with surgical implants. Moreover, the tetrameric structure promotes efficient binding to bacterial lipopolysaccharide (LPS), significantly reducing local inflammation. These effects, combined with direct antibacterial activity against Gram-positive and Gram-negative bacteria, including some resistant strains (E. coli LC711/14, K. pneumoniae colR), make these AMPs promising therapeutic agents against infections.