PL‐101‐WK, a novel tryptophan‐ and lysine‐rich peptide with antimicrobial activity against Staphylococcus aureus

Abstract

Designing short antimicrobial peptides (AMPs), which are active against drug‐resistant bacteria, is a promising way to find new therapeutic agents. In this research, a novel short AMP, PL‐101‐WK, was designed based on PL‐101 (a derivative of plicatamide). Here, the substitution of Phe and His with Trp and Lys was considered. The antimicrobial activity and physicochemical properties of PL‐101‐WK were compared with PL‐101 by in silico analysis. The antimicrobial activity in the presence or absence of NaCl concentration, thermal stability, hemolytic activity, and selectivity of the peptides were determined. By substitution of Lys and Trp residues, positive charge, in vitro stability, and hydrophilicity of PL‐101‐WK were raised compared to the template. PL‐101‐WK had the best minimum inhibitory concentration (MIC) value of 64 μg/ml against Staphylococcus aureus strains, which showed at least 16‐fold reduction when compared to the values of PL‐101. The MICs of PL‐101‐WK were retained toward S. aureus strains at physiological salt concentration. While PL‐101‐WK did not display acceptable thermal stability, it had desirable selectivity against bacteria. The maximum hemolytic activity of PL‐101‐WK was 1.65% at 512 μg/ml. Taken together, increasing positive charge and the presence of Trp residues were enhanced the potential of antibacterial activity of PL‐101.

Optimizing Bothropstoxin-I-Derived Peptides: Exploring the Antibacterial Potential of p-BthW

“… 13 , 14 In addition, several studies show a relationship between this amino acid and increased antimicrobial activity without increasing hemolytic activity. 14 − 17 …”

“…The suggested alteration for this peptide was based on the relationship between tryptophan and antimicrobial activity. This amino acid plays a crucial role in proteins and peptides interacting with membranes. , In addition, several studies show a relationship between this amino acid and increased antimicrobial activity without increasing hemolytic activity. − …”

Designer tryptophan‐rich peptide modulates structural dynamics of HIF‐1α DNA i‐motif DNA

“…Studies have shown that oligopeptides containing aromatic amino acids can form stacked complexes with DNA 22 . For example, a W‐rich peptide (PL‐101‐WK) has been shown to exhibit antibacterial activity and drug candidates 23,24 . A tripeptide (KWK) has also been demonstrated to be complex with single‐stranded and double‐stranded DNA sequences through stacking interactions 25 .…”

“…22 For example, a W-rich peptide (PL-101-WK) has been shown to exhibit antibacterial activity and drug candidates. 23,24 A tripeptide (KWK) has also been demonstrated to be complex with single-stranded and double-stranded DNA sequences through stacking interactions. 25 Fluorescence studies have revealed two types of complexations between KWK and DNA: direct interaction of the indole ring (W) with nucleobases leading to fluorescence quenching, and electrostatic interaction between K (cationic)…”