Abstract
Derivatization of protein-based therapeutics with polyethylene glycol (pegylation) can often improve pharmacokinetic and pharmacodynamic properties of the proteins and thereby, improve efficacy and minimize dosing frequency. This review will provide an overview of pegylation technology and pegylated protein-based drugs being used or investigated clinically. The novel therapeutic, PEG Intron, formed by attaching a 12-kDa mono-methoxy polyethylene glycol (PEG) to the interferon alpha-2b protein, will be discussed in detail in terms of its structure, biological activities, pharmacokinetic properties, and clinical efficacy for the treatment of chronic hepatitis C. Detailed physicochemical and biological characterization studies of PEG Intron revealed its composition of pegylated positional isomers and the specific anti-viral activity associated with each of them. Pegylation of Intron A at pH 6.5 results in a mixture of ≥ 95% mono-pegylated isoforms with the predominant species (approximately 50 %) derivatized to the His34 residue with the remaining positional isomers pegylated at various lysines, the N-terminal cysteine, as well as serine, tyrosine, and another histidine residue. The anti-viral activity for each pegylated isomer showed that the highest specific activity (37%) was associated with the His34-pegylated isomer. Though pegylation decreases the specific activity of the interferon alpha-2b protein in vitro, the potency of PEG Intron was comparable to the Intron A standard at both the molecular and cellular level. The substituted IFN had an enhanced pharmacokinetic profile in both animal and human studies, and, when combined with ribavirin, was very effective in reducing hepatitis C viral load and maintaining sustained viral suppression in patients.
Keywords: hepatitic c, pegylated positional isomer, pegylated protein-based therapeutics, protein-polymer conjugate, pegylated interferon, interferon alpha-2b
Current Pharmaceutical Design
Title: Structure, Biology, and Therapeutic Implications of Pegylated Interferon Alpha-2b
Volume: 8 Issue: 24
Author(s): Stephen Youngster, Yu-Sen Wang, Michael Grace, James Bausch, Ronald Bordens and Daniel F. Wyss
Affiliation:
Keywords: hepatitic c, pegylated positional isomer, pegylated protein-based therapeutics, protein-polymer conjugate, pegylated interferon, interferon alpha-2b
Abstract: Derivatization of protein-based therapeutics with polyethylene glycol (pegylation) can often improve pharmacokinetic and pharmacodynamic properties of the proteins and thereby, improve efficacy and minimize dosing frequency. This review will provide an overview of pegylation technology and pegylated protein-based drugs being used or investigated clinically. The novel therapeutic, PEG Intron, formed by attaching a 12-kDa mono-methoxy polyethylene glycol (PEG) to the interferon alpha-2b protein, will be discussed in detail in terms of its structure, biological activities, pharmacokinetic properties, and clinical efficacy for the treatment of chronic hepatitis C. Detailed physicochemical and biological characterization studies of PEG Intron revealed its composition of pegylated positional isomers and the specific anti-viral activity associated with each of them. Pegylation of Intron A at pH 6.5 results in a mixture of ≥ 95% mono-pegylated isoforms with the predominant species (approximately 50 %) derivatized to the His34 residue with the remaining positional isomers pegylated at various lysines, the N-terminal cysteine, as well as serine, tyrosine, and another histidine residue. The anti-viral activity for each pegylated isomer showed that the highest specific activity (37%) was associated with the His34-pegylated isomer. Though pegylation decreases the specific activity of the interferon alpha-2b protein in vitro, the potency of PEG Intron was comparable to the Intron A standard at both the molecular and cellular level. The substituted IFN had an enhanced pharmacokinetic profile in both animal and human studies, and, when combined with ribavirin, was very effective in reducing hepatitis C viral load and maintaining sustained viral suppression in patients.
Export Options
About this article
Cite this article as:
Youngster Stephen, Wang Yu-Sen, Grace Michael, Bausch James, Bordens Ronald and Wyss F. Daniel, Structure, Biology, and Therapeutic Implications of Pegylated Interferon Alpha-2b, Current Pharmaceutical Design 2002; 8 (24) . https://dx.doi.org/10.2174/1381612023393242
DOI https://dx.doi.org/10.2174/1381612023393242 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- 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
-
Molecular Targeting in Pancreatic Cancer
Reviews on Recent Clinical Trials Fabrication and Physicochemical and Medicinal Characterization of Nano Traditional Chinese Medicine
Recent Patents on Engineering Management of Hypertension in Relation to Acute Coronary Syndromes and Revascularisation
Current Pharmaceutical Design Anaphylaxis in Risky Populations
Current Pharmaceutical Design Hepatic AMP Kinase as a Potential Target for Treating Nonalcoholic Fatty Liver Disease: Evidence from Studies of Natural Products
Current Medicinal Chemistry The Role of Major Histocompatibility Complex Polymorphisms in the Incidence and Outcome of Non-Hodgkin Lymphoma
Current Immunology Reviews (Discontinued) Patent Selections:
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery PPAR-γ Agonists in Polycystic Kidney Disease with Frequent Development of Cardiovascular Disorders
Current Molecular Pharmacology Insights of Valacyclovir in Treatment of Alzheimer’s Disease: Computational Docking Studies and Scopolamine Rat Model
Current Neurovascular Research Role of Cytokines in Regulating Feeding Behaviour
Current Drug Targets Heterocyclic Compounds as Inflammation Inhibitors
Current Medicinal Chemistry A Novel Approach to Label-Free Sensing: Diffractive Optics Technology (dot®)
Combinatorial Chemistry & High Throughput Screening Association between the Use of Inhaled Corticosteroids and Pulmonary Nontuberculous Mycobacterial Infection: A Systematic Review
Current Respiratory Medicine Reviews Does Inhaled Corticosteroid Treatment Result in a Secondary Immune Deficiency Predisposing To Recurrent Infections?
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Seasonal and Perennial Allergic Conjunctivitis
Recent Patents on Inflammation & Allergy Drug Discovery Steroid Receptor-Associated Immunophilins: Candidates for Diverse Drug-Targeting Approaches in Disease
Current Molecular Pharmacology Plant and Animal Steroids a New Hope to Search for Antiviral Agents
Current Medicinal Chemistry First Steps Towards a Vaccine against Acinetobacter baumannii
Current Pharmaceutical Biotechnology Preface
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) Anti-Hypertensive Potential and Epigenetics of Angiotensin II type 2 Receptor (AT2R)
Current Hypertension Reviews