Oxidation of acetylacetone catalyzed by horseradish peroxidase in the absence of hydrogen peroxide.
Horseradish peroxidase (HRP) is a plant enzyme widely used in biotechnology, including antibody-directed enzyme prodrug therapy (ADEPT). Here, we showed that HRP is able to catalyze the autoxidation of acetylacetone in the absence of hydrogen peroxide. This autoxidation led to generation of methylglyoxal and reactive oxygen species. The production of superoxide anion was evidenced by the effect of superoxide dismutase and by the generation of oxyperoxidase during the enzyme turnover. The HRP has a high specificity for acetylacetone, since the similar beta-dicarbonyls dimedon and acetoacetate were not oxidized. As this enzyme prodrug combination was highly cytotoxic for neutrophils and only requires the presence of a non-human peroxidase and acetylacetone, it might immediately be applied to research on the ADEPT techniques. The acetylacetone could be a starting point for the design of new drugs applied in HRP-related ADEPT techniques.
Rodrigues
Ana Paula
AP
Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista, Araraquara, SP, Brazil.
da Fonseca
Luiz Marcos
LM
de Faria Oliveira
Olga M
OM
Brunetti
Iguatemy Lourenço
IL
Ximenes
Valdecir Farias
VF
D002384:Catalysis; D006735:Horseradish Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D010422:Pentanones / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
D010422:Pentanones; C008790:acetylacetone; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase