Potent Antimicrobial Activity of Lipidated Short α,γ‐Hybrid Peptides

Abstract

Herein we report the potent antimicrobial activity of α,γ-hybrid lipopeptides composed of 1:1 alternating α- and γ-amino acids. Along with their potent antimicrobial activity against various Gram-positive and Gram-negative bacteria, these hybrid lipopeptides were found to be less hemolytic. Studies into the mechanism of action revealed that these short cationic lipopeptides bind and disrupt the bacterial cell membrane. Time-kill kinetics analyses revealed that the potent α,γ-hybrid lipopeptides completely inhibit bacterial growth in less than 20 minutes. Overall, the promising antimicrobial activity along with lower hemolytic activity displayed by these α,γ-hybrid lipopeptides make them well suited for further exploration into the design of potent lipopeptide antibiotics.

Designing Self‐Assembling Chimeric Peptide Nanoparticles with High Stability for Combating Piglet Bacterial Infections

“…As a novel type of antibiotic substitute, lipopeptides have the advantages of a broad antimicrobial spectrum, high biocompatibility, and low toxicity. [ 4 ] Additionally, unlike antibiotics (that selectively interfere with specific steps of bacterial metabolism), most peptide‐based antibacterial drugs exert their antibacterial effects by physically destroying the lipid bilayers of bacteria, which makes it difficult for the bacteria to develop resistance. [ 5 ] However, most peptide‐based antibacterial drugs are unstable, easily interfered with by anionic substances, and easily degraded by proteases under physiological conditions; this severely restricts the therapeutic effects of peptide‐based antibacterial drugs.…”

Helical Antimicrobial Peptide Foldamers Containing Non‐proteinogenic Amino Acids

“…Short α/γ-hybrid antimicrobial peptides were reported by Gopi and co-workers. [83] The α/γ-hybrid peptides containing α-Lys and γ-Leu residues showed potent antimicrobial activity by inhibiting the growth of bacteria, causing a change to cell morphology and disrupting bacterial membranes.…”

Sequence-Defined Synthetic Polymers for New-Generation Functional Biomaterials

“…Such results strongly supported that the capability to form a facially amphipathic helix was not a prerequisite for selective antibacterial activity, representing a significant advance in the design of antibacterial foldamers. On the other hand, Gopi et al , explored the antimicrobial properties of lipidated hybrid peptides containing alternating sequences of α-amino acids and E -vinylogous γ-amino acids or γ-amino acids. In striking contrast to α-peptide counterparts, such hybrid peptides exhibited excellent antimicrobial efficacy against various bacterial and fungal pathogens. , …”

“…On the other hand, Gopi et al , explored the antimicrobial properties of lipidated hybrid peptides containing alternating sequences of α-amino acids and E -vinylogous γ-amino acids or γ-amino acids. In striking contrast to α-peptide counterparts, such hybrid peptides exhibited excellent antimicrobial efficacy against various bacterial and fungal pathogens. , …”

“…In striking contrast to α-peptide counterparts, such hybrid peptides exhibited excellent antimicrobial efficacy against various bacterial and fungal pathogens. 74,75 In 2002, DeGrado et al 44 reported the biomimetic design and synthesis of arylamide-backboned discrete oligomers (Figure 3a) and polydisperse polymers with the facially amphiphilic feature. The precision oligomers had better antibacterial activity against both Gram-negative Klebsiella pneumoniae (K. pneumoniae) and E. coli and Gram-positive Bacillus subtilis (B. subtilis) bacteria than that of a synthetically modified magainin II derivative.…”