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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances of Heterocyclic Chemistry with Pesticide Activity
Global food safety and security will continue to be a global concern for the next 50 years and beyond. Plant diseases have had a significant impact on food safety and security throughout the entire food chain, from primary production to consumption. While conventional chemical pesticides have been traditionally used for ...read more
Calculation design of covalent/metal organic framework based catalysts
This research area combines theoretical computation and screening with machine learning for the design of covalent/metal organic framework-based catalysts, bridging the disciplines of organic chemistry, physical chemistry, computational chemistry, materials science, and machine learning. It covers several critical aspects: designing and synthesizing organic catalysts for improved performance, applying computational methods ...read more
Carbohydrates conversion in biofuels and bioproducts
Biomass pretreatment, hydrolysis, and saccharification of carbohydrates, and sugars bioconversion in biofuels and bioproducts within a biorefinery framework. Carbohydrates derived from woody biomass, agricultural wastes, algae, sewage sludge, or any other lignocellulosic feedstock are included in this issue. Simulation, techno-economic analysis, and life cycle analysis of a biorefinery process are ...read more
Catalytic C-H bond activation as a tool for functionalization of heterocycles
The major topic is the functionalization of heterocycles through catalyzed C-H bond activation. The strategies based on C-H activation not only provide straightforward formation of C-C or C-X bonds but, more importantly, allow for the avoidance of pre-functionalization of one or two of the cross-coupling partners. The beneficial impact of ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Pain-Relief Medication and Risk of Fractures
Current Drug Safety Antinociceptive Effects of Aza-Bicyclic Isoxazoline-Acylhydrazone Derivatives in Different Models of Nociception in Mice
Current Topics in Medicinal Chemistry A1 Receptors Ligands: Past, Present and Future Trends
Current Topics in Medicinal Chemistry Therapeutic Modulation of Glutamate Receptors in Major Depressive Disorder
Current Neuropharmacology Endocannabinoids and Their Receptors: Physiology, Pathology and Pharmacology
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) A Role for Leptin in the Systemic Inflammatory Response Syndrome (SIRS) and in Immune Response, an Update
Current Medicinal Chemistry L-Dopa Prodrugs: An Overview of Trends for Improving Parkinsons Disease Treatment
Current Pharmaceutical Design Novel Antiinflammatory and Antiinfective Agents
Anti-Infective Agents in Medicinal Chemistry Telomere/Telomerase System: A New Target of Statins Pleiotropic Effect?
Current Vascular Pharmacology Drug Treatment of Metabolic Syndrome
Current Clinical Pharmacology Why is the Inhibition of the Renin-Angiotensin System Effective for Preventing Cardiac Events in Patients with Coronary Risk Factors or Coronary Artery Disease?
Current Cardiology Reviews Microwave Assisted Medicinal Chemistry
Mini-Reviews in Medicinal Chemistry Epidemiology of Major Congenital Malformations with Specific Focus on Teratogens
Current Drug Safety Novel Perspective for Antithrombotic Therapy in TAVI
Current Pharmaceutical Design Interrelationship between Chronic Kidney Disease and Risk of Cardiovascular Diseases
Cardiovascular & Hematological Agents in Medicinal Chemistry Neuropsychiatric and General Interactions of Natural and Synthetic Cannabinoids with Drugs of Abuse and Medicines
CNS & Neurological Disorders - Drug Targets Sacubitril/Valsartan: A New Dawn has Begun! A Revisited Review
Current Cardiology Reviews Salusins in Hypertension and Related Cardiovascular Diseases
Current Drug Metabolism Autonomic Neural Functions in Space
Current Pharmaceutical Biotechnology Dopamine Administration in Very Low Birth Weight Preterm Infants:Emerging Issues on Endocrine Effects
Current Pediatric Reviews