Structure-Activity Relations of Myxinidin, an Antibacterial Peptide Derived from the Epidermal Mucus of Hagfish

Abstract

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.

Differential In Vitro and In Vivo Toxicities of Antimicrobial Peptide Prodrugs for Potential Use in Cystic Fibrosis

“…Pro-WMR shows superiority to the previous group of pro-AMPs, exhibiting a lower level of cytotoxicity against CFBE cells, CFTE cells, and neutrophils. This is in agreement with the low level of cytotoxicity against Vero cells originally seen with L-WMR by others (25,26). The cleaved peptide AAG-WMR was not as active against P. aeruginosa as AG-HB43 or AAG-P18 (16), but the reduced toxicity compensated for this.…”

“…In addition, high salt tolerance would facilitate the delivery of these AMPs with hypertonic saline, the inhalation of which reduces airway mucus plugging in mice with CF-like lung disease and improves lung function in patients with CF (40)(41)(42). However, while the cleaved peptides were more active against P. aeruginosa than the pro-AMPs, it must be noted that their activity tended to be less than that previously reported in the literature; i.e., MIC values were 64 g/ml, whereas they were 3.3 g/ml for L-WMR (26). The differences in MICs may be due to the use of different strains and assay conditions.…”

“…It demonstrated high levels of activity against P. aeruginosa and low levels of cytotoxicity against human cells (24)(25)(26). Another AMP chosen for prodrug modification, WR12, comes from a series of salt-resistant peptides synthesized by Deslouches et al (27,28).…”

Structural Insights into and Activity Analysis of the Antimicrobial Peptide Myxinidin

“…Since the rational design of AMPs represents a straightforward approach to obtaining a peptide with better therapeutic characteristics, an analysis of the structural elements responsible for the antimicrobial action of myxinidin was initiated (16). Here, to address the influence of each amino acid residue of myxinidin on its antimicrobial activity, an alanine scanning analysis was carried out, together with the synthesis of novel analogues.…”

An integrated study on antimicrobial activity and ecotoxicity of quantum dots and quantum dots coated with the antimicrobial peptide indolicidin

“…Indolicidin (Ac-NH-ILPWKWPWWPWRR-COOH) was synthesized using the standard solid-phase 9-fluorenylmethoxycarbonyl method as previously reported 41 on a scale of 100 μmol. Briefly, peptides were obtained using a Wang (0.58 mmol/g) resin by consecutive deprotection (30% piperidine) and coupling (2 equivalents of amino acid, 2 equivalents of HOBT/HBTU, and 4 equivalents of DIPEA).…”