Design, solid phase synthesis and evaluation of cationic ferrocenoyl peptide bioconjugates as potential antioxidant enzyme mimics

Bioorg Med Chem Lett. 2009 Feb 15;19(4):1173-6. doi: 10.1016/j.bmcl.2008.12.084. Epub 2008 Dec 25.

Abstract

Synthetic C-terminal amidated cationic ferrocenoyl peptide bioconjugates Fc-Orn-Orn-Orn (1) and Fc-Tyr-Orn-Orn-Orn (2) were rationally designed as superoxide dismutase (SOD) mimics based on the structure of the iron SOD from Escherichia coli. Ferrocenoyl peptide bioconjugates 1, 2 and ferrrocenecarboxylic acid (4) were subsequently evaluated as SOD mimics and as inhibitors of peroxynitrite-mediated tyrosine nitration. Due to their cationic character, ferrocenoyl peptide bioconjugates 1 and 2 exerted an acceptable SOD activity (EC(50)=575 microM and 310 microM, respectively) in comparison with 4 (EC(50)=1.4mM). The C-terminal amidated cationic peptide Ac-Tyr-Orn-Orn-Orn (3), designed as marker of peroxynitrite, was used to evaluate the inhibitory activity of 1 and 4 towards peroxynitrite-mediated tyrosine nitration. Both compounds proved to inhibit the nitration especially the cationic ferrocenoyl peptide bioconjugates 1. The ferrocene moiety of conjugate 2 displayed a strong inhibitory activity of peroxynitrite-mediated nitration of the neighboring tyrosine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemical synthesis*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Drug Design
  • Escherichia coli / enzymology*
  • Ferrous Compounds / chemical synthesis*
  • Ferrous Compounds / chemistry
  • Ferrous Compounds / pharmacology*
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Protein Conformation
  • Superoxide Dismutase / chemistry*
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Fc-Orn-Orn-Orn
  • Fc-Tyr-Orn-Orn-Orn
  • Ferrous Compounds
  • Oligopeptides
  • Superoxide Dismutase