Off-target activity of TNF-alpha inhibitors characterized by protein biochips.
Anal Bioanal Chem
; 391(5): 1713-20, 2008 Jul.
Article
en En
| MEDLINE
| ID: mdl-18344017
ABSTRACT
Tumor necrosis factor-alpha inhibitors are widely and successfully used to treat rheumatic diseases. However, significant side effects have been reported. To detect the potential off-target activities of such inhibitors we characterized two therapeutic antibodies (adalimumab, infliximab) and one receptor fusion protein (etanercept) on protein biochips (UNIchip AV-400) containing a printed serial dilution of tumor necrosis factor-alpha and about 384 different human proteins. Etanercept binds to ten proteins (affinity 20-33% of tumor necrosis factor-alpha recognition), and six of these proteins are related to ribosomal proteins. Interestingly, adalimumab binds to the same six proteins related to ribosomal proteins (affinity 12-18%) as well as to four proteins crucially involved in ribosomal protein synthesis. Alignment of protein sequences indicates no significant sequence homology between these ten proteins bound by the biological drugs with the highest off-target activities. Taken together, our in vitro results demonstrate that a significant number of proteins are recognized by tumor necrosis factor-alpha inhibitors and are related to ribosome biogenesis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inmunoglobulina G
/
Factor de Necrosis Tumoral alfa
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Antirreumáticos
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Análisis por Matrices de Proteínas
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Anticuerpos Monoclonales
Límite:
Humans
Idioma:
En
Revista:
Anal Bioanal Chem
Año:
2008
Tipo del documento:
Article
País de afiliación:
Alemania