PEGylation of therapeutic proteins

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PEGylation of therapeutic proteins.

Since the first PEGylated product was approved by the Food and Drug Administration in 1990, PEGylation has been widely used as a post-production modification methodology for improving biomedical efficacy and physicochemical properties of therapeutic proteins. Applicability and safety of this technology have been proven by use of various PEGylated pharmaceuticals for many years. It is expected t...

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Site-Specific PEGylation of Therapeutic Proteins

The use of proteins as therapeutics has a long history and is becoming ever more common in modern medicine. While the number of protein-based drugs is growing every year, significant problems still remain with their use. Among these problems are rapid degradation and excretion from patients, thus requiring frequent dosing, which in turn increases the chances for an immunological response as wel...

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Site-specific PEGylation of native disulfide bonds in therapeutic proteins.

Native disulfide bonds in therapeutic proteins are crucial for tertiary structure and biological activity and are therefore considered unsuitable for chemical modification. We show that native disulfides in human interferon alpha-2b and in a fragment of an antibody to CD4(+) can be modified by site-specific bisalkylation of the two cysteine sulfur atoms to form a three-carbon PEGylated bridge. ...

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Disulfide bridge based PEGylation of proteins.

PEGylation is a clinically proven strategy for increasing the therapeutic efficacy of protein-based medicines. Our approach to site-specific PEGylation exploits the thiol selective chemistry of the two cysteine sulfur atoms from an accessible disulfide. It involves two key steps: (1) disulfide reduction to release the two cystine thiols, and (2) bis-alkylation to give a three-carbon bridge to w...

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Site-specific PEGylation of proteins containing unnatural amino acids.

Here, we report a generally applicable PEGylation methodology based on the site-specific incorporation of para-azidophenylalanine into proteins in yeast. The azido group was used in a mild [3+2] cycloaddition reaction with an alkyne derivatized PEG reagent to afford selectively PEGylated protein. This strategy should be useful for the generation of selectively PEGylated proteins for therapeutic...

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ژورنال

عنوان ژورنال: Biotechnology Journal

سال: 2010

ISSN: 1860-6768,1860-7314

DOI: 10.1002/biot.200900218