Biochemical and biopharmaceutical properties of PEGylated uricase
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International Journal of Pharmaceutics
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PEGylation is a successful strategy for improving the biochemical and biopharmaceutical properties of proteins and peptides through the covalent attachment of polyethylene glycol chains. In this work, purified recombinant uricase from Candida sp. (UC-r) was modified by PEGylation with metoxypolyethilenoglycol-p-nitrophenyl-carbonate (mPEG-pNP) and metoxypolyethyleneglycol-4,6dichloro-s-triazine (mPEG-CN). The UC-r-mPEG-pNP and UC-r-mPEG-CN conjugates retained 87% and 75% enzyme activity respectively. The KM values obtained 2.7×10−5M (mPEG-pNP) or 3.0×10−5M (mPEG-CN) for the conjugates as compared to 5.4×10−5M for the native UC-r, suggesting enhancement in the substrate affinity of the enzyme attached. The effects of pH and temperature on PEGylated UC-r indicated that the conjugates were more active at close physiological pH and were stable up to 70◦C. Spectroscopic study performed by circular dichroism at 20◦C and 50◦C did not show any relevant difference in protein structure between native and PEGylated UC-r. In rabbit and Balb/c mice, the native UC-r elicited an intense immune response being highly immunogenic. On the other hand, the PEGylated UC-r when injected chronically in mice did not induce any detectable antibody response. This indicates sufficient reduction of the immunogenicity this enzymebymPEG-pNPormPEG-CNconjugation,making it suitable for a possible therapeutical use.
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FREITAS, DEBORA da S.; SPENCER, PATRICK J.; VASSAO, RUTH C.; ABRAHAO NETO, JOSE. Biochemical and biopharmaceutical properties of PEGylated uricase. International Journal of Pharmaceutics, v. 387, n. 1-2, p. 215-222, 2010. DOI: 10.1016/j.ijpharm.2009.11.034. Disponível em: http://repositorio.ipen.br/handle/123456789/4720. Acesso em: 30 Dec 2025.
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