Design of multifunctional peptides expressing both antimicrobial activity and shiga toxin neutralization activity

Yoshinao Yamada, Yoshiko Miura, Akio Sakaki, Tetsuhiko Yoshida, Kazukiyo Kobayashi

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

We have designed novel short peptides expressing both antimicrobial and Shiga-toxin (Stx) neutralization activities by combining nuclear localization signal (NLS) peptides (RIRKKLR, PKKKRKV, and PRRRK) tandemly with globotriaoside (Gb3) mimic peptide (WHWTWL). These fusion peptides exhibited excellent antimicrobial activity against both gram-positive and gram-negative bacteria. A peptide WHWTWLRIRKKLR (Trp-His-Trp-Thr-Trp-Leu-Arg-Ile-Arg-Lys-Lys-Leu-Arg), especially, exhibited about 100 times higher activity than the original NLS peptide. SPR analysis demonstrated that the binding of this peptide to both Stxs was strong: Kd = 6.6 × 10-6 to Stx-1 and 6.8 × 10-6 to Stx-2. The in vitro assay against Stx-1 using HeLa cells showed that this peptide increased the survival rate of HeLa cells against the infection of Stx-1. The peptide has been found to maintain high antimicrobial activity, Stx neutralization activity, and no cytotoxicity at its concentration of 7.8-31.3 μg/mL (4.2-16.7 μM). The present peptide design has a prospect of developing potent multifunctional drugs to destroy proteinaceous toxin-producing bacteria and to simultaneously neutralize the toxins released by bacteriolysis.

Original languageEnglish
Pages (from-to)77-82
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 1 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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