Characteristics of novel insect defensin-based membrane-disrupting trypanocidal peptides

Mat Yamage, Mikio Yoshiyama, Dennis J. Grab, Masanori Kubo, Takashi Iwasaki, Hiroshi Kitani, Jun Ishibashi, Minoru Yamakawa

Research output: Contribution to journalArticlepeer-review

Abstract

Synthetic D- and L-amino acid type cationic 9-mer peptides (all sequences were synthesized as D- or Lamino acids) derived from the active sites of insect defensins were tested for their ability to modify the growth of blood-stream form African trypanosomes in vitro. One of them, the D-type peptide A (RLYLRIGRRNH2), irreversibly suppressed proliferation of the Trypanosoma brucei brucei GUTat3.1 parasite. The presence of negatively charged phosphatidylserine on the surface of the parasites was demonstrated, suggesting electrostatic interaction between the peptide and the phospholipids. Furthermore, this peptide was found to alter trypanosome membrane-potentials significantly, an effect apparently due to the removal of the parasite's plasma membrane. The potential toxic effects of Dpeptide A on mammalian cells was assessed using human brain microvascular endothelial cells. Only minor effects were found when the endothelial cells were exposed for 16 h to peptide concentrations of less than 200μM. These findings suggest that insect defensinbased peptides represent a potentially new class of membrane-disrupting trypanocidal drugs.

Original languageEnglish (US)
Pages (from-to)1520-1526
Number of pages7
JournalBioscience, Biotechnology and Biochemistry
Volume73
Issue number7
DOIs
StatePublished - 2009

Keywords

  • Insect defensins
  • Phospholipids
  • Synthetic peptides
  • T.b. brucei
  • Trypanocidal activity

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Applied Microbiology and Biotechnology
  • Analytical Chemistry
  • Organic Chemistry

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