title: Bioinspired superoxide-dismutase mimics: The effects of functionalization with cationic polyarginine peptides.
abstract: 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 Mn(II) with association constants (Kassoc) between 1.6 and 3.3×10(6)M(-1). The Mn(III)/Mn(II) redox potential of the conjugates was between 0.27 and 0.30V vs SCE, slightly higher than [MnL](+) under the same conditions, but remain at a value that facilitates O2(-) 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±0.1×10(6)M(-1)s(-1)) led to a lower value (i.e. for [MnL'Gly](+), kcat=4.2±0.1×10(6)M(-1)s(-1)). However, under the same conditions, kcat values between 5.0±0.4×10(6)M(-1)s(-1) and 6.6±0.1×10(6)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.
authors.affiliation: École Normale Supérieure, PSL Research University, Département de chimie, 24 rue Lhomond, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005 Paris, France; CNRS, LBM, UMR 7203, 75005 Paris, France.
authors.forename: H Y Vincent
authors.initials: HY
authors.lastname: Ching
authors.affiliation: Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg, Egerlandstr. 1, 91058 Erlangen, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Kenkel
authors.affiliation: École Normale Supérieure, PSL Research University, Département de chimie, 24 rue Lhomond, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005 Paris, France; CNRS, LBM, UMR 7203, 75005 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delsuc
authors.affiliation: École Normale Supérieure, PSL Research University, Département de chimie, 24 rue Lhomond, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005 Paris, France; CNRS, LBM, UMR 7203, 75005 Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mathieu
authors.affiliation: Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg, Egerlandstr. 1, 91058 Erlangen, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Ivanović-Burmazović
authors.affiliation: École Normale Supérieure, PSL Research University, Département de chimie, 24 rue Lhomond, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005 Paris, France; CNRS, LBM, UMR 7203, 75005 Paris, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Policar
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D003959:Diamines / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D007700:Kinetics; D008345:Manganese / Q000737:chemistry*; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*; D055672:Static Electricity; D013482:Superoxide Dismutase / Q000737:chemistry*; D013481:Superoxides / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D001555:Benzene Derivatives; D056831:Coordination Complexes; D003959:Diamines; D007093:Imidazoles; D010455:Peptides; D013481:Superoxides; C015462:polyarginine; D008345:Manganese; D013482:Superoxide Dismutase
keywords: Manganese complexes; Peptide conjugate; SOD activity; SOD mimetics; SOD mimics; Superoxide