Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates

Abstract

DMPC-10A (ALWKKLLKK-Cha-NH2) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala1 and Trp3 remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae using the Galleria mellonella larva model and displayed synergistic activities with gentamicin against carbapenem-resistant K. pneumoniae strains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens.

In Vitro & In Vivo Studies on Identifying and Designing Temporin-1CEh from the Skin Secretion of Rana chensinensis as the Optimised Antibacterial Prototype Drug

“…In the test of their antimicrobial and haemolytic activities, both peptides completely lost antimicrobial and haemolytic activity. The C-terminus was not chosen as the later modification position because it was discovered that this area lacks the selectivity between antimicrobial activity and haemolytic activity, even anticancer activity, in previous and this study [ 26 , 27 ].…”

“…ESKAPE pathogens, encompassing six pathogens which exhibit multidrug resistance and lead nosocomial infections, were used to determine the antibacterial activity of Temporin-1CEh and its analogues by using broth dilution method [ 26 ], including Gram-positive bacteria, S. aureus (ATCC CRM 6538), MRSA (NCTC 12493) and E. faecalis (NCTC 12697), Gram-negative bacteria, E. coli (NCTC 10418), P. aeruginosa (ATCC 27853) and K. pneumoniae (ATCC 43816). A measure of 5 × 10 5 CFU/mL of bacterial suspension including 2-fold dilution peptides (ranging from 1 µM to 512 µM) was incubated in 96-well plates for 16–20 h at 37 °C.…”

Generation of truncated derivatives through in silico enzymatic digest of peptide GV30 target MRSA both in vitro and in vivo

“…The assessment of in vivo antimicrobial activity of GV30 and its derivatives was performed using the larvae of Galleria mellonella [38] . The infection model was constructed by injecting 10 μl of MRSA (NCTC 12493) bacterial suspension (1 × 10 7 CFU/ml) prepared in PBS.…”

“…The debris and impurities of the erythrocytes were washed with PBS in advance of making a 2 % v/v erythrocyte suspension, and the peptide concentrations were prepared from 512 µM to 2 µM in PBS [38] . Peptides and the erythrocyte suspension were mixed and cultured at 37 °C for 2 h and 0.1% Triton X-100 (Sigma-Aldrich, St. Louis, MO, USA) was prepared as a positive control, and PBS was prepared as a negative control.…”

Modification Strategy of D-leucine Residue Addition on a Novel Peptide from Odorrana schmackeri, with Enhanced Bioactivity and In Vivo Efficacy

“… a From [ 17 ]; b HC 50 is the concentration of the tested peptides that caused 50% haemolysis of the horse red blood cells; NA: Not applicable. …”