Plant Antimicrobial Peptides snakin-1 and snakin-2: Chemical Synthesis and Insights Into the Disulfide Connectivity

Chemistry. 2014 Apr 22;20(17):5102-10. doi: 10.1002/chem.201303207. Epub 2014 Mar 18.

Abstract

Antimicrobial peptides and proteins represent an important class of plant defensive compounds against pathogens and provide a rich source of lead compounds in the field of drug discovery. We describe the effective preparation of the cysteine-rich snakin-1 and -2 antimicrobial peptides by using a combination of solid-phase synthesis and native chemical ligation. A subsequent cysteine/cystine mediated oxidative folding to form the six internal disulfide bonds concurrently gave the folded proteins in 40-50 % yield. By comparative evaluation of mass spectrometry, HPLC, biological data and trypsin digest mapping of folded synthetic snakin-2 compared to natural snakin-2, we demonstrated that synthetic snakin-2 possesses full antifungal activity and displayed similar chromatographic behaviour to natural snakin-2. Trypsin digest analysis allowed tentative assignment of three of the purported six disulfide bonds.

Keywords: antibiotics; natural products; peptides; solid-phase synthesis; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Infective Agents / chemical synthesis*
  • Anti-Infective Agents / chemistry
  • Biological Products / chemical synthesis*
  • Biological Products / chemistry
  • Cysteine / chemistry
  • Cystine / chemistry
  • Disulfides / chemistry
  • Molecular Sequence Data
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Plant Proteins / chemical synthesis*
  • Plant Proteins / chemistry
  • Protein Folding
  • Solanum tuberosum / chemistry*
  • Solid-Phase Synthesis Techniques

Substances

  • Anti-Infective Agents
  • Biological Products
  • Disulfides
  • Peptides
  • Plant Proteins
  • SN1 protein, Solanum tuberosum
  • Cystine
  • Cysteine