title: Cyclodecapeptides to mimic the radical site of tyrosyl-containing proteins.
abstract: Tyrosyl radicals are involved in many biologically important processes. The development of model compounds to mimic radical enzyme active sites, such as galactose oxidase (GO), has widely contributed to an enhanced understanding of their spectral properties, structural attributes and even reactivity. An emerging approach towards the synthesis of such active site mimetics is the use of peptidic ligands. The potential of cyclodecapeptides to bear phenoxyl radicals has been evaluated through three compounds. LH(4) (2+) is a cyclodecapetide containing two histidine residues (mimicking His(496) and His(581) of GO) and two tyrosine residues (mimicking Tyr(495) and the Tyr(272)* radical of GO). L(tBu)H(4) (2+) and L(OMe)H(4) (2+) incorporate 2,4,6-protected phenols in place of each tyrosine in LH(4) (2+). The deprotonation constants of each peptide determined by potentiometric titrations showed that there are some interactions between the acido-basic residues. Cyclic voltammetric studies revealed that only the peptides incorporating 2,4,6-protected phenolates exhibit reversible redox couples and are thus precursors of radicals stable enough to persist in solution. These studies also showed L(OMe2-) to possess the lower oxidation potential, indicating that this peptide, in its radical form, is the most stabilized. The electrochemically generated radical species have been characterized by EPR spectroscopy.
authors.affiliation: Laboratoire de Chimie Biomimétique, LEDSS, UMR CNRS 5616, ICMG FR CNRS 2607, Université J. Fourier, BP 53, 38041, Grenoble Cedex 9, France.
authors.forename: Mohammed Akhter
authors.initials: MA
authors.lastname: Hossain
authors.forename: Fabrice
authors.initials: F
authors.lastname: Thomas
authors.forename: Sylvain
authors.initials: S
authors.lastname: Hamman
authors.forename: Eric
authors.initials: E
authors.lastname: Saint-Aman
authors.forename: Didier
authors.initials: D
authors.lastname: Boturyn
authors.forename: Pascal
authors.initials: P
authors.lastname: Dumy
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pierre
mesh_terms: D001665:Binding Sites; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000737:chemistry; D005692:Galactose Oxidase / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D008024:Ligands; D018716:Molecular Mimicry; D010084:Oxidation-Reduction; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry; D011199:Potentiometry; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D005609:Free Radicals; D008024:Ligands; D010456:Peptides, Cyclic; D010636:Phenols; C514953:cyclo(glycyl-prolyl-N(epsilon)-(3,5-bis(tert-butyl)-2-hydroxybenzoyl)lysyl-alanyl-N(epsilon)-(3,5-bis(tert-butyl)-2-hydroxybenzoyl)lysyl-glycyl-prolyl-histidyl-alanyl-histidyl); C514954:cyclo(glycyl-prolyl-N(epsilon)-(3-(tert-butyl)-2-hydroxy-5-methoxybenzoyl)lysyl-alanyl-N(epsilon)-(3-(tert-butyl)-2-hydroxy-5-methoxybenzoyl)lysyl-glycyl-prolyl-histidyl-alanyl-histidyl); C514952:cyclo(glycyl-prolyl-tyrosyl-alanyl-tyrosyl-glycyl-prolyl-histidyl-alanyl-histidyl); D014443:Tyrosine; D006639:Histidine; D005692:Galactose Oxidase