title: Structural insights into and activity analysis of the antimicrobial peptide myxinidin.
abstract: The marine environment has been poorly explored in terms of potential new molecules possessing antibacterial activity. Antimicrobial peptides (AMPs) offer a new potential class of pharmaceuticals; however, further optimization is needed if AMPs are to find broad use as antibiotics. We focused our studies on a peptide derived from the epidermal mucus of hagfish (Myxine glutinosa L.), which was previously characterized and showed high antimicrobial activity against human and fish pathogens. In the present work, the activities of myxinidin peptide analogues were analyzed with the aim of widening the original spectrum of action of myxinidin by suitable changes in the peptide primary structure. The analysis of key residues by alanine scanning allowed for the design of novel peptides with increased activity. We identified the amino acids that are of the utmost importance for the observed antimicrobial activities against a set of pathogens comprising both Gram-negative and Gram-positive bacteria. Overall, optimized bactericidal potency was achieved by adding a tryptophan residue at the N terminus and by the simultaneous substitution of residues present in positions 3, 4, and 11 with arginine. These results indicate that the myxinidin analogues emerge as an attractive alternative for treating drug-resistant infectious diseases and provide key insights into a rational design for novel agents against these pathogens.
authors: Department of Pharmacy, CIRPEB, and DFM, University of Naples Federico II, Naples, Italy Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy Center for Advanced Materials for Healthcare IIT@CRIB, Istituto Italiano di Tecnologia, Naples, Italy.
authors: Marco
authors: M
authors: Cantisani
authors: Department of Experimental Medicine, II University of Naples, Naples, Italy.
authors: Emiliana
authors: E
authors: Finamore
authors: Department of Experimental Medicine, II University of Naples, Naples, Italy.
authors: Eleonora
authors: E
authors: Mignogna
authors: Department of Pharmacy, CIRPEB, and DFM, University of Naples Federico II, Naples, Italy Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy.
authors: Annarita
authors: A
authors: Falanga
authors: Dipartimento Multidisciplinare di Specialità Medico-Chirurgiche e Odontoiatriche, II University of Naples, Naples, Italy.
authors: Giovanni Francesco
authors: GF
authors: Nicoletti
authors: Department of Pharmacy, CIRPEB, and DFM, University of Naples Federico II, Naples, Italy Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy.
authors: Carlo
authors: C
authors: Pedone
authors: Department of Pharmacy, CIRPEB, and DFM, University of Naples Federico II, Naples, Italy Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy.
authors: Giancarlo
authors: G
authors: Morelli
authors: Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy.
authors: Marilisa
authors: M
authors: Leone
authors: Department of Experimental Medicine, II University of Naples, Naples, Italy massimiliano.galdiero@unina2.it stefania.galdiero@unina.it.
authors: Massimiliano
authors: M
authors: Galdiero
authors: Department of Pharmacy, CIRPEB, and DFM, University of Naples Federico II, Naples, Italy Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy massimiliano.galdiero@unina2.it stefania.galdiero@unina.it.
authors: Stefania
authors: S
authors: Galdiero
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects; D029941:Fish Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007711:Klebsiella pneumoniae / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012485:Salmonella typhi / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D029941:Fish Proteins; D009842:Oligopeptides; C000601319:myxinidin peptide, Myxine glutinosa