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
-
Naturally Occurring Hydroxytyrosol: Synthesis and Anticancer Potential
Current Medicinal Chemistry Adoptive Regulatory T-cell Therapy Attenuates Subarachnoid Hemor-rhage-induced Cerebral Inflammation by Suppressing TLR4/NF-B Signaling Pathway
Current Neurovascular Research Fibromyalgia Syndrome: Which Antidepressant Drug Should We Choose
Current Pharmaceutical Design The Optimal Treatment of Severe Hypertension in Pregnancy: Update of the Role of Nicardipine
Current Pharmaceutical Biotechnology Monitoring the Pharmacokinetics of Pyridinium Aldoximes in the Body
Mini-Reviews in Medicinal Chemistry An Overview of Neolignans of the Genus Piper L.: Isolation Methods and Biological Activities
Mini-Reviews in Medicinal Chemistry Anesthetic Neuroprotection: Antecedents and An Appraisal of Preclinical and Clinical Data Quality
Current Pharmaceutical Design Bacterial Toxins: Potential Weapons Against HIV Infection
Current Pharmaceutical Design From the Stretcher to the Pharmacys Shelf: Drug Leads from Medically Important Brazilian Venomous Arachnid Species
Inflammation & Allergy - Drug Targets (Discontinued) The Hemodynamics of Septic Shock: A Historical Perspective
Current Vascular Pharmacology The Use of Biomarkers for Assessing HAART-Associated Renal Toxicity in HIV-Infected Patients
Current HIV Research Recent Highlights on Molecular Hybrids Potentially Useful in Central Nervous System Disorders
Mini-Reviews in Medicinal Chemistry Biochemical Markers in the Prediction of Contrast-induced Acute Kidney Injury
Current Medicinal Chemistry Dipeptidyl-peptidase 4 Inhibition: Linking Metabolic Control to Cardiovascular Protection
Current Pharmaceutical Design Cyclin Dependent Kinase 1 Inhibitors: A Review of Recent Progress
Current Medicinal Chemistry Impulsive and Compulsive Behaviors During Dopamine Replacement Treatment in Parkinson’s Disease and Other Disorders
Current Drug Safety Fatal Disseminated Toxoplasmosis During Primary HIV Infection
Current HIV Research Inhibitors of Nitric Oxide Synthase: What's up and What's Next?
Current Enzyme Inhibition Comparison of Dapaglifozin and Liraglutide in Patients with Poorly Controlled Type 2 Diabetes Mellitus: a 24-week, Open, Double-centered, Head to Head Trial
Endocrine, Metabolic & Immune Disorders - Drug Targets Near Infrared Spectroscopy in Healthy Preterm and Term Newborns: Correlation with Gestational Age and Standard Monitoring Parameters
Current Neurovascular Research