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- W2084587462 endingPage "472" @default.
- W2084587462 startingPage "461" @default.
- W2084587462 abstract "In the recent years, protein PEGylation has become an established and highly refined technology by moving forward from initial simple random coupling approaches based on conjugation at the level of lysine ε-amino group. Nevertheless, amino PEGylation is still yielding important conjugates, currently in clinical practice, where the degree of homogeneity was improved by optimizing the reaction conditions and implementing the purification processes. However, the current research is mainly focused on methods of site-selective PEGylation that allow the obtainment of a single isomer, thus highly increasing the degree of homogeneity and the preservation of bioactivity. Protein N-terminus and free cysteines were the first sites exploited for selective PEGylation but currently further positions can be addressed thanks to approaches like bridging PEGylation (disulphide bridges), enzymatic PEGylation (glutamines and C-terminus) and glycoPEGylation (sites of O- and N-glycosylation or the glycans of a glycoprotein). Furthermore, by combining the tools of genetic engineering with specific PEGylation approaches, the polymer can be basically coupled at any position on the protein surface, owing to the substitution of a properly chosen amino acid in the sequence with a natural or unnatural amino acid bearing an orthogonal reactive group. On the other hand, PEGylation has not achieved the same success in the delivery of small drugs, despite the large interest and several studies in this field. Targeted conjugates and PEGs for combination therapy might represent the promising answers for the so far unmet needs of PEG as carrier of small drugs. This review presents a thorough panorama of recent advances in the field of PEGylation." @default.
- W2084587462 created "2016-06-24" @default.
- W2084587462 creator A5020606836 @default.
- W2084587462 creator A5036102891 @default.
- W2084587462 date "2012-07-01" @default.
- W2084587462 modified "2023-10-13" @default.
- W2084587462 title "State of the art in PEGylation: The great versatility achieved after forty years of research" @default.
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