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

Laurent Soulère (1) , Julien Bernard (2)

1 ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires
2 IMP-LMM - Ingénierie des Matériaux Polymères - Laboratoire des Matériaux Macromoléculaires

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 (EC50 = 575 μM and 310 μM, respectively) in comparison with 4 (EC50 = 1.4 mM). 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.

Domaines: Polymères

Laurent Soulère, Julien Bernard. Rational design, solid phase synthesis and evaluation of cationic ferrocenoyl peptide bioconjugates as potential antioxidant enzyme mimics. Bioorganic and Medicinal Chemistry Letters, 2009, 19 (4), pp.1173-1176. ⟨10.1016/j.bmcl.2008.12.084⟩. ⟨hal-00374569⟩