Designing the antimicrobial peptide with centrosymmetric and amphipathic characterizations for improving antimicrobial activity

J Pept Sci. 2023 Nov;29(11):e3510. doi: 10.1002/psc.3510. Epub 2023 May 15.

Abstract

Antibiotic-resistant bacterial infections are becoming a serious health issue and will cause 10 million deaths per year by 2050. As a result, the development of new antimicrobial agents is urgently needed. Antimicrobial peptides (AMPs) are found in the innate immune systems of various organisms to effectively fend off invading pathogens. In this study, we designed a series of AMPs (THL-2-1 to THL-2-9) with centrosymmetric and amphipathic properties, through substituting different amino acids on the hydrophobic side and at the centrosymmetric position to improve their antimicrobial activity. The results showed that leucine as a residue on the hydrophobic side of the peptide could enhance its antimicrobial activity and that glutamic acid as a centrosymmetric residue could increase the salt resistance of the peptide. Thus, the THL-2-3 peptide (KRLLRELKRLL-NH2 ) showed the greatest antimicrobial activity (MIC90 of 16 μM) against Gram-negative bacteria and had the highest salt resistance and cell selectivity among all the designed peptides. In summary, the results of this study provide useful references for the design of AMPs to enhance antimicrobial activity.

Keywords: amphipathicity; antimicrobial peptide; centrosymmetric; hydramacin-1; hydrophobic.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents* / pharmacology
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology
  • Antimicrobial Peptides*
  • Bacteria
  • Microbial Sensitivity Tests
  • Protein Structure, Secondary

Substances

  • Antimicrobial Peptides
  • Antimicrobial Cationic Peptides
  • Anti-Infective Agents
  • Anti-Bacterial Agents