Structural contributions to the intracellular targeting strategies of antimicrobial peptides

Biochim Biophys Acta. 2010 Oct;1798(10):1934-43. doi: 10.1016/j.bbamem.2010.07.003. Epub 2010 Jul 15.

Abstract

The interactions of cationic amphipathic antimicrobial peptides (AMPs) with anionic biological membranes have been the focus of much research aimed at improving the activity of such compounds in the search for therapeutic leads. However, many of these peptides are thought to have other polyanions, such as DNA or RNA, as their ultimate target. Here a combination of fluorescence and circular dichroism (CD) spectroscopies has been used to assess the structural properties of amidated versions of buforin II, pleurocidin and magainin 2 that support their varying abilities to translocate through bacterial membranes and bind to double stranded DNA. Unlike magainin 2 amide, a prototypical membrane disruptive AMP, buforin II amide adopts a poorly helical structure in membranes closely mimicking the composition of Gram negative bacteria, such as Escherichia coli, and binds to a short duplex DNA sequence with high affinity, ultimately forming peptide-DNA condensates. The binding affinities of the peptides to duplex DNA are shown to be related to the structural changes that they induce. Furthermore, CD also reveals the conformation of the bound peptide buforin II amide. In contrast with a synthetic peptide, designed to adopt a perfect amphipathic alpha-helix, buforin II amide adopts an extended or polyproline II conformation when bound to DNA. These results show that an alpha-helix structure is not required for the DNA binding and condensation activity of buforin II amide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Amino Acid Sequence
  • Animals
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / metabolism
  • Anti-Infective Agents / pharmacology
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / metabolism*
  • Antimicrobial Cationic Peptides / pharmacology
  • Bacteria / drug effects
  • Bacteria / genetics
  • Bacteria / growth & development
  • Binding, Competitive
  • Circular Dichroism
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / metabolism*
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Fish Proteins / chemistry
  • Fish Proteins / metabolism
  • Fish Proteins / pharmacology
  • Magainins / chemistry
  • Magainins / metabolism
  • Magainins / pharmacology
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / metabolism*
  • Peptides / pharmacology
  • Protein Binding
  • Protein Structure, Secondary
  • Proteins / chemistry
  • Proteins / metabolism
  • Proteins / pharmacology
  • Spectrometry, Fluorescence

Substances

  • Amides
  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • DNA, Bacterial
  • Fish Proteins
  • Magainins
  • Peptides
  • Proteins
  • buforin II
  • pleurocidin