Cationic Helical Peptide Research Articles

Antibacterial activity of active peptide from marine macroalgae Chondrus crispus protein hydrolysate against Staphylococcus aureus

Macroalgae is a protein source with the potential to yield antimicrobial peptides (AMPs) that exhibit a wide range of biological activities. This study aimed to find bioactive peptide-based antibacterial compounds from marine macroalgae Chondrus crispus protein hydrolysate. The peptides were isolated by solid phase extraction with a strong cation exchanger from trypsin-digested and α-chymotrypsin-digested hydrolysates. Certain fractions of the hydrolyzed protein displayed a good inhibition zone, with the α-chymotrypsin-digested fraction eluted at pH 9 exhibiting the highest inhibition against Gram-negative bacteria Staphylococcus aureus. Several peptides were characterized as cationic helical peptides with hydrophobicity percentages of 16.67–77.78%. The potential antibacterial peptide P01 KKNVTTLAPLVF was identified as an α-helical cationic antibacterial peptide with 0.525 GRAVY value, amphipathic structure, and +2 total charge. Moreover, strong interaction was observed between P07 SAGSGNEGLSGW and P20 RTASSR peptide with DNA gyrase and DHFR receptors from S. aureus with binding energy -8.0 and -7.3 kcal/mol, respectively.

The effect of thiol functional group incorporation into cationic helical peptides on antimicrobial activities and spectra

Antimicrobial peptides (AMP) have been proposed as blueprints for the development of new antimicrobial agents for the treatment of drug resistant infections. A series of synthetic AMPs capable of forming α-helical structures and containing free-sulfhydryl groups are designed in this study ((LLKK) 2C, C(LLKK) 2C, (LLKK) 3C, C(LLKK) 3C). In particular, the AMP with 2 cysteine residues at the terminal ends of the peptide and 2 repeat units of LLKK, i.e., C(LLKK) 2C, has been demonstrated to have high selectivity towards a wide range of microbes from Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, Pseudomonas aerogenosa, and yeast Candida albicans over red blood cells. At the MIC levels, this peptide does not induce significant hemolysis, and its MIC values occur at the concentration of more than 10 times of their corresponding 50% hemolysis concentrations (HC 50). Microscopy studies suggest that this peptide kills microbial cells by inducing pores of ∼20–30 nm in size in microbial membrane on a short time scale, which further develops to grossly damaged membrane envelope on a longer time scale. Multiple treatments of microbes with this peptide at sub MIC concentration do not induce resistance, even up to passage 10. However, the same treatment with conventional antibiotics penicillin G or ciprofloxacin easily develop resistance in the treated microbes. In addition, the peptides are shown not to induce secretion of IFN-γ and TNF-α in human monocytes as compared to lipopolysaccharide, which implies additional safety aspects of the peptides to be used as both systemic and topical antimicrobial agents. Therefore, this study provides an excellent basis to develop promising antimicrobial agents that possess a broad range of antimicrobial activities with less susceptibility for development of drug resistance.