PEGylation of bacterial cocaine esterase for protection against protease digestion and immunogenicity

Jun Beom Park, Young Min Kwon, Tien Yi Lee, Remy Brim, Mei Chuan Ko, Roger K. Sunahara, James H. Woods, Victor C. Yang

Resultado de la investigación: Articlerevisión exhaustiva

29 Citas (Scopus)

Resumen

Enhancing cocaine metabolism by administration of cocaine esterase (CocE) has been considered as a promising treatment strategy for cocaine overdose and addiction, as CocE is the most efficient native enzyme yet identified for metabolizing the naturally occurring cocaine. A major obstacle to the clinical application of CocE, however, lies in its thermo-instability, rapid degradation by circulating proteases, and potential immunogenicity. PEGylation, namely by modifying a protein or peptide compound via attachment of polyethylene glycol (PEG) chains, has been proven to overcome such problems and was therefore exploited in this CocE investigation.The PEG-CocE conjugates prepared in this study showed a purity of greater than 93.5%. Attachment of PEG to CocE apparently inhibited the binding of anti-CocE antibodies to the conjugate, as demonstrated by the enzyme-linked immunosorbent assay (ELISA) assay. In addition, PEGylation yielded protection to CocE against thermal degradation and protease digestion. Furthermore, preliminary in vivo results suggested that, similarly to native CocE, the PEG-CocE conjugates were able to protect animals from cocaine-induced toxic effects. Overall, this study provides evidence that the PEGylation may serve as a tool to prolong CocE functionality in the circulation and reduce its potential immunogenicity.

Idioma originalEnglish (US)
Páginas (desde-hasta)174-179
Número de páginas6
PublicaciónJournal of Controlled Release
Volumen142
N.º2
DOI
EstadoPublished - mar. 2010
Publicado de forma externa

ASJC Scopus subject areas

  • Pharmaceutical Science

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