Abstract
The covalent attachment of methoxy-poly(ethylene glycol) (mPEG) is a well established strategy used to improve the pharmaceutical properties of several biomolecules. Since the pioneering work of Abuchovsky, PEGylation has emerged as a powerful technology of significant relevance, not only for the development of new and better drugs, but also for application in material science. Peptides and proteins are the most traditional targets for PEGylation due to their intense and diverse biotechnological applications. The terminal amino group, as well as the ε-amino group of lysine and the thiol group of cysteine, are all well known nucleophilic sites that have traditionally been used to couple peptides and proteins to mPEG derivatives. Advances in the methods for preparation of the mPEG starting materials, together with a careful selection of new mPEG functional end-groups have allowed new reactive mPEGs to emerge, which show narrow polydispersity and controlled reactivity, providing more homogeneous conjugates. In the last few years the trend has moved towards site-selective, reversible and enzymatic PEGylation using a new generation of tailor-made reagents and strategies. The main goal of this article is to present some of the most relevant achievements obtained in the PEGylation of peptides and proteins. The chemistry underlying the current methods used for the preparation of mPEG reagents, as well as the chemistry involved in the PEGylation reactions are presented in detail, in order of stimulating the synthetic and polymer chemist to turn their attention in this fascinating multi and interdisciplinary field of research.
Keywords: PEGylation, Poly(ethylene glycol), PEG reagents, Conjugation, Protein PEGylation, Controlled drug release, Activated PEG.
Current Organic Chemistry
Title:Evolution of Reactive mPEG Polymers for the Conjugation of Peptides and Proteins
Volume: 17 Issue: 9
Author(s): Marianela Gonzalez and Santiago E. Vaillard
Affiliation:
Keywords: PEGylation, Poly(ethylene glycol), PEG reagents, Conjugation, Protein PEGylation, Controlled drug release, Activated PEG.
Abstract: The covalent attachment of methoxy-poly(ethylene glycol) (mPEG) is a well established strategy used to improve the pharmaceutical properties of several biomolecules. Since the pioneering work of Abuchovsky, PEGylation has emerged as a powerful technology of significant relevance, not only for the development of new and better drugs, but also for application in material science. Peptides and proteins are the most traditional targets for PEGylation due to their intense and diverse biotechnological applications. The terminal amino group, as well as the ε-amino group of lysine and the thiol group of cysteine, are all well known nucleophilic sites that have traditionally been used to couple peptides and proteins to mPEG derivatives. Advances in the methods for preparation of the mPEG starting materials, together with a careful selection of new mPEG functional end-groups have allowed new reactive mPEGs to emerge, which show narrow polydispersity and controlled reactivity, providing more homogeneous conjugates. In the last few years the trend has moved towards site-selective, reversible and enzymatic PEGylation using a new generation of tailor-made reagents and strategies. The main goal of this article is to present some of the most relevant achievements obtained in the PEGylation of peptides and proteins. The chemistry underlying the current methods used for the preparation of mPEG reagents, as well as the chemistry involved in the PEGylation reactions are presented in detail, in order of stimulating the synthetic and polymer chemist to turn their attention in this fascinating multi and interdisciplinary field of research.
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Cite this article as:
Gonzalez Marianela and Vaillard Santiago E., Evolution of Reactive mPEG Polymers for the Conjugation of Peptides and Proteins, Current Organic Chemistry 2013; 17 (9) . https://dx.doi.org/10.2174/1385272811317090010
DOI https://dx.doi.org/10.2174/1385272811317090010 |
Print ISSN 1385-2728 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5348 |
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