RESUMEN
The superoxide dismutase activities of two novel synthetic chelating peptides are reported. The peptides comprise a polyaminocarboxylic acid chelator (EDTA) conjugated to tyrosine (ET(1)) and phenylalanine (EP(1)). Superoxide dismutase (SOD) activity was exhibited for Cu(II) but not the Fe(III) complexes. The mimetic activities were compared to bovine erythrocyte SOD (3730 U/mg) and exhibited activities of 1119 U/mg for ET(1)-Cu(II) and 551 U/mg for EP(1)-Cu(II). Thus, small alterations in structure can have significant effects on the enzymatic activity of metallopeptides. These synthetic chelators have dual potential anti-inflammatory activity by chelating deleterious non-protein bound metal ions and concomitantly affording anti-oxidant mimetic activity.
Asunto(s)
Antioxidantes/química , Materiales Biomiméticos/química , Quelantes/química , Ácido Edético/análogos & derivados , Depuradores de Radicales Libres/química , Superóxido Dismutasa/química , Antioxidantes/farmacología , Materiales Biomiméticos/farmacología , Quelantes/síntesis química , Quelantes/farmacología , Depuradores de Radicales Libres/farmacología , Quelantes del Hierro/química , Quelantes del Hierro/farmacología , Relación Estructura-Actividad , Superóxido Dismutasa/farmacologíaRESUMEN
Reactive oxygen and nitrogen species (RONS) have been ascribed an important role in oxidative stress contributing to the progression of inflammatory diseases such as Crohn's disease and rheumatoid arthritis. Redox-active metal ions such as Fe(II) and Cu(I) further activate RONS and thus perpetuate their damaging effects. High intake of ascorbic acid exerts a pro-oxidant effect by its interaction with metal ions via a number of established RONS generating systems. Caution should be exerted regarding surplus ascorbic acid intake for patients with chronic inflammatory diseases.
Asunto(s)
Ácido Ascórbico/fisiología , Radicales Libres , Ácido Ascórbico/metabolismo , Cobre/metabolismo , Progresión de la Enfermedad , Humanos , Inflamación , Iones , Hierro/metabolismo , Modelos Químicos , Modelos Teóricos , Oxidantes/metabolismo , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Novel peptoids useful for the detection and suppression of various components contributing to oxidative stress and for elucidation of the interplay between these species are presented. Oxidative stress involves redox-active metal ion activation/generation of RONS (reactive oxygen and nitrogen species). For detection of RONS, the peptoid probes consist of a conjugate designed to (1) complex redox-active and non-redox-active metal ions, and (2) differentiate between RONS based upon the reaction products following RONS attack on the probe. For suppression of RONS, subtle modifications in peptoid structure impart catalase and superoxide dismutase activities to the peptoids upon ferric or cupric ion complexation.