Positional scanning library applied to the human eosinophil cationic protein/RNase3 N-terminus reveals novel and potent anti-biofilm peptides

European Journal of Medicinal Chemistry
David PulidoEster Boix

Abstract

Eradication of established biofilm communities of pathogenic bacteria is one of the pending challenges in the development of new antimicrobial agents. In particular, the dreaded nosocomial Pseudomonas aeruginosa forms microbial communities that offer an enhanced resistance to conventional antibiotics. Recently, we have described an engineered antimicrobial peptide derived from the human RNase3, also named the eosinophil cationic protein (ECP), RN3 (5-36), which combines bactericidal activity with high cell agglutination and lipopolysaccharide (LPS) affinity. Through a single replacement scan library using the SPOT methodology we have evaluated both the contribution of sequence positioning and amino acid singularity towards the peptide biological and physicochemical properties. Results indicate that the ECP N-terminus has already been extensively improved through evolution to provide high antimicrobial activity; hence most substitutions improving its antimicrobial performance are in detriment of safety towards host tissues. Only three positions were identified, occupied by polar residues on the first α-helix of the protein and replaceable by a hydrophobic residue, allowing an extended N-terminal patch that mediates bacterial agg...Continue Reading

Citations

Mar 4, 2020·Current Topics in Medicinal Chemistry·Jiarui LiEster Boix
Sep 22, 2019·International Journal of Molecular Sciences·Vivian A SalazarEster Boix
Jul 6, 2019·Frontiers in Microbiology·Guillem Prats-EjarqueEster Boix
Dec 19, 2019·International Journal of Molecular Sciences·Nicole TrierGunnar Houen

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