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Title

Study of protein haptenation by amoxicillin through the use of a biotinylated antibiotic

AuthorsAriza, Adriana; Collado, Daniel; Vida, Yolanda; Montañez, M. I.; Pérez-Inestrosa, Ezequiel; Blanca, Miguel; Torres, María J.; Cañada, F. Javier ; Pérez-Sala, Dolores
Issue Date3-Mar-2014
PublisherPublic Library of Science
CitationPLoS ONE 9(3): e90891
AbstractAllergic reactions towards b-lactam antibiotics pose an important clinical problem. The ability of small molecules, such as a b-lactams, to bind covalently to proteins, in a process known as haptenation, is considered necessary for induction of a specific immunological response. Identification of the proteins modified by b-lactams and elucidation of the relevance of this process in allergic reactions requires sensitive tools. Here we describe the preparation and characterization of a biotinylated amoxicillin analog (AX-B) as a tool for the study of protein haptenation by amoxicillin (AX). AX-B, obtained by the inclusion of a biotin moiety at the lateral chain of AX, showed a chemical reactivity identical to AX. Covalent modification of proteins by AX-B was reduced by excess AX and vice versa, suggesting competition for binding to the same targets. From an immunological point of view, AX and AX-B behaved similarly in RAST inhibition studies with sera of patients with non-selective allergy towards b-lactams, whereas, as expected, competition by AX-B was poorer with sera of AX-selective patients, which recognize AX lateral chain. Use of AX-B followed by biotin detection allowed the observation of human serum albumin (HSA) modification by concentrations 100-fold lower that when using AX followed by immunological detection. Incubation of human serum with AX-B led to the haptenation of all of the previously identified major AX targets.In addition, some new targets could be detected. Interestingly, AX-B allowed the detection of intracellular protein adducts, which showed a cell type-specific pattern. This opens the possibility of following the formation and fate of AX-B adducts in cells. Thus, AX-B may constitute a valuable tool for the identification of AX targets with high sensitivity as well as for the elucidation of the mechanisms involved in allergy towards b-lactams.
Description12 p.-9 fig.-2 tab.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pone.0090891
URIhttp://hdl.handle.net/10261/98420
DOI10.1371/journal.pone.0090891
ISSN1932-6203
E-ISSN1932-6203
Appears in Collections:(CIB) Artículos
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