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

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

研究成果: Contribution to journalArticle査読

14 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)77-82
ページ数6
ジャーナルBioorganic and Medicinal Chemistry
14
1
DOI
出版ステータス出版済み - 1 1 2006
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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