Influences of disulfide connectivity on structure and antimicrobial activity of tachyplesin I

J Pept Sci. 2018 Jun;24(6):e3087. doi: 10.1002/psc.3087.

Abstract

Tachyplesin I is a potent antimicrobial peptide with broad spectrum of antimicrobial activity. It has 2 disulfide bonds and can form 3 disulfide bond isomers. In this study, the structure and antimicrobial activity of 3 tachyplesin I isomers (tachyplesin I, 3C12C, 3C7C) were investigated using molecular dynamic simulations, circular dichroism structural study, as well as antimicrobial activity and hemolysis assay. Our results suggest that in comparison to the native peptide, the 2 isomers (3C12C, 3C7C) have substantial structural and activity variations. The native peptide is in the ribbon conformation, while 3C12C and 3C7C possess remarkably different secondary structures, which are referred as "globular" and "beads" isomers, respectively. The substantially decreased hemolysis effects for these 2 isomers is accompanied by significantly decreased anti-gram-positive bacterial activity.

Keywords: antimicrobial activity; antimicrobial peptide; disulfide connectivity; secondary structure; tachyplesin I.

MeSH terms

  • Amino Acid Sequence / genetics
  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / pharmacology
  • Antimicrobial Cationic Peptides / chemistry*
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / pharmacology
  • Circular Dichroism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / pharmacology
  • Disulfides / chemistry
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / pathogenicity
  • Microbial Sensitivity Tests
  • Molecular Dynamics Simulation
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / genetics
  • Peptides, Cyclic / pharmacology
  • Protein Conformation / drug effects
  • Protein Structure, Secondary
  • Structure-Activity Relationship

Substances

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • DNA-Binding Proteins
  • Disulfides
  • Peptides, Cyclic
  • tachyplesin peptide, Tachypleus tridentatus