Structure-activity relations of myxinidin, an antibacterial peptide derived from the epidermal mucus of hagfish.

The structure-activity relations of myxinidin, a peptide derived from epidermal mucus of hagfish, Myxine glutinosa L., were investigated. Analysis of key residues allowed us to design new peptides with increased efficiency. Antimicrobial activity of native and modified peptides demonstrated the key role of uncharged residues in the sequence; the loss of these residues reduces almost entirely myxinidin antimicrobial activity, while insertion of arginine at charged and uncharged position increases antimicrobial activity compared with that of native myxinidin. Particularly, we designed a peptide capable of achieving a high inhibitory effect on bacterial growth. Experiments were conducted using both Gram-negative and Gram-positive bacteria. Nuclear magnetic resonance (NMR) studies showed that myxinidin is able to form an amphipathic -helical structure at the N terminus and a random coil region at the C terminus. T he extensive use of broad-spectrum antibiotics has led to the emergence of resistance to classical antibiotics for many bacterial human pathogens and has posed a major threat to global health care. Effective infection control measures and development of new classes of antimicrobial agents with lower rates of resistance development necessitate extensive efforts and are urgently required (1, 2). Antimicrobial peptides (AMPs) are an essential part of the innate immune response, with both direct microbicidal and pleiotropic immunomodulatory properties (3, 4). The ubiquitous presence of AMPs in nature (microorganisms, insects, invertebrates, amphibians, plants, birds, and mammals) (5–7) attests to their key role in building the defense strategies of most organisms. AMPs may display similar modes of action against a wide range of microbes and share several properties. In addition to microbicidal capabilities, certain peptides also confer diverse functions that have an impact on the quality and effectiveness of the innate immune responses and inflammation (8).