Bioinspired superoxide-dismutase mimics: The effects of functionalization with cationic polyarginine peptides

H.Y. Vincent Ching (1, 2) , Isabell Kenkel (3) , Nicolas Delsuc (4, 1) , Emilie Mathieu (1, 2) , Ivana Ivanović-Burmazović (3) , Clotilde Policar (1, 4)

1 PSL - Université Paris Sciences et Lettres
2 UPMC - Université Pierre et Marie Curie - Paris 6
3 Department of Chemistry and Pharmacy
4 LBM-E1 - Peptides, glycoconjugués et métaux en biologie

Continuing a bio-mimetic approach, we have prepared peptide conjugates of a superoxide dismutase (SOD) mimic [MnL]+ (where HL = N-(2-hydroxybenzyl)-N,N′-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine), namely [MnL′-Arg(n − 1)]n + (where n = 2, 4, 7 and 10) and [MnL′-Gly1]+. [MnL′-Arg(n − 1)]n + contained cationic residue(s) that emulate the electrostatic channel of the enzyme. Physicochemical methods showed that functionalization at the secondary amine of HL did not impair coordination to MnII with association constants (Kassoc) between 1.6 and 3.3 × 106 M− 1. The MnIII/MnII redox potential of the conjugates was between 0.27 and 0.30 V vs SCE, slightly higher than [MnL]+ under the same conditions, but remain at a value that facilitates O2radical dot− dismutation. The catalytic rate constant (kcat) of the dismutation for the series was studied using a direct stopped-flow method, which showed that for compounds with the same overall charge, the alkylation of the secondary amine of [MnL]+ (kcat = 5.0 ± 0.1 × 106 M− 1 s− 1) led to a lower value (i.e. for [MnL′Gly]+, kcat = 4.2 ± 0.1 × 106 M− 1 s− 1). However, under the same conditions, kcat values between 5.0 ± 0.4 × 106 M− 1 s− 1 and 6.6 ± 0.1 × 106 M− 1 s− 1 were determined for [MnL′-Arg(n − 1)]n + conjugates, indicating that the cationic residue(s) compensated for the loss in activity. Analysis of the effect of ionic strength on the kcat strongly suggested that not all the charges were involved, but only the closest ones electrostatically influenced the SOD active metal centre.

Mots clés: SOD mimetics; SOD mimics; Manganese complexes; Superoxide; SOD activity; Peptide conjugate

Domaines: Chimie

H.Y. Vincent Ching, Isabell Kenkel, Nicolas Delsuc, Emilie Mathieu, Ivana Ivanović-Burmazović, et al.. Bioinspired superoxide-dismutase mimics: The effects of functionalization with cationic polyarginine peptides. Journal of Inorganic Biochemistry, 2016, 160, pp.172-179. ⟨10.1016/j.jinorgbio.2016.01.025⟩. ⟨hal-01288188⟩