Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Site Directed Disulfide Pegylation of Interferon-Β-1B With Fork Peptide Linker Publisher Pubmed



Abbasi S1, 2 ; Farahani H3 ; Lanjanian H1 ; Taheri M2 ; Firoozpour L4 ; Davoodi J1 ; Pirkalkhoran S5 ; Riazi G1 ; Pooyan S1, 2
Authors
Show Affiliations
Authors Affiliations
  1. 1. Institute of Biochemistry and Biophysics, University of Tehran, PO Code 1417614335, Tehran, Iran
  2. 2. Rooyan Darou Pharmaceutical Company, PO Code 15996-89111, Tehran, Iran
  3. 3. Department of Microbiology, School of Biology, Faculty of Science, University of Tehran, PO Code 1417466191, Tehran, Iran
  4. 4. Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, PO Code 14174, Tehran, Iran
  5. 5. Department of Biology, Faculty of Basic Science, Islamic Azad University, Central Tehran Branch, PO Code 1477893855, Tehran, Iran

Source: Bioconjugate Chemistry Published:2020


Abstract

The attachment of PEG to biopharmaceuticals has been applied for enhancement of bioavailability and improved stability. The PEG polymer is highly hydrated; thus effective attachment to inaccessible sites could be hindered. We have devised a scheme to address this issue by introducing a considerable distance between PEG and protein by addition of a linear peptide, appended to long chained reactive linkers. Second, the position of PEG conjugation directly affects biological activity. Accordingly, a disulfide bond could be considered as an ideal choice for site directed PEGylation; but reactivity of both thiol moieties to bridging reagent is critical for maintenance of protein structure. In our design, a forked structure with two arms provides essential flexibility to account for dissociation of reduced cysteines. An efficient yield for disulfide PEGylation of IFN-β1b was attained and specificity, biophysical characterization, biological activity, and pharmacokinetics were surveyed. Copyright © 2020 American Chemical Society.
Related Docs
View other Related Docs
1. An Albumin-Free Formulation for Escherichia Coli-Derived Interferon Beta-1B With Decreased Immunogenicity in Immune Tolerant Mice, Journal of Interferon and Cytokine Research (2016)
2. Immunogenicity of Recombinant Human Interferon Beta-1B in Immune-Tolerant Transgenic Mice Corresponds With the Biophysical Characteristics of Aggregates, Journal of Interferon and Cytokine Research (2016)
3. Insights Into the Molecular-Level Details of Betaine Interactions With Laccase Under Various Thermal Conditions, Journal of Molecular Liquids (2021)
4. Effect of Nonionic Surfactants (Dodecyl Maltoside and Polysorbate 20) on Prevention of Aggregation and Conformational Changes of Recombinant Human Ifnβ_1B Induced by Light, Iranian Journal of Pharmaceutical Research (2017)
5. Molecular Level Insight Into Stability, Activity, and Structure of Laccase in Aqueous Ionic Liquid and Organic Solvents: An Experimental and Computational Research, Journal of Molecular Liquids (2020)
6. Molecular Insight Into Cof Monolayers for Urea Sorption in Artificial Kidneys, Scientific Reports (2021)
7. Functional Deimmunization of Interferon Beta-1B by Identifying and Silencing Human T Cells Epitopes, Iranian Journal of Allergy# Asthma and Immunology (2019)
8. Discovery of Potential Fgfr3 Inhibitors Via Qsar, Pharmacophore Modeling, Virtual Screening and Molecular Docking Studies Against Bladder Cancer, Journal of Translational Medicine (2023)
Experts (# of related papers)
View all Related Experts
Mohammad Reza Fazeli (4)
Mohammad Reza Khorramizadeh (3)
Other Related Docs
9. Rational Approaches to Discover Sars-Cov-2/Ace2 Interaction Inhibitors: Pharmacophore-Based Virtual Screening, Molecular Docking, Molecular Dynamics and Binding Free Energy Studies, Journal of Molecular Liquids (2023)
10. In Silico Evidence for Prednisone and Progesterone Efficacy in Recurrent Implantation Failure Treatment, Journal of Molecular Modeling (2022)
11. Investigation for Antimicrobial Resistance-Modulating Activity of Diethyl Malate and 1-Methyl Malate Against Beta-Lactamase Class a From Bacillus Licheniformis by Molecular Dynamics, in Vitro and in Vivo Studies, Journal of Biomolecular Structure and Dynamics (2015)
12. Inhibition of Sars-Cov-2 Pathogenesis by Potent Peptides Designed by the Mutation of Ace2 Binding Region, Computers in Biology and Medicine (2022)
13. Repurposing of the Approved Small Molecule Drugs in Order to Inhibit Sars-Cov-2 S Protein and Human Ace2 Interaction Through Virtual Screening Approaches, Journal of Biomolecular Structure and Dynamics (2022)
14. Monoterpenes As Nitrofurantoin Resistance Modulating Agents: Minimal Structural Requirements, Molecular Dynamics Simulations, and the Effect of Piperitone on the Emergence of Nitrofurantoin Resistance in Enterobacteriaceae, Journal of Molecular Modeling (2015)
15. In Silico Identification of New Inhibitors for Βeta-2-Glycoprotein I As a Major Antigen in Antiphospholipid Antibody Syndrome, Journal of Molecular Modeling (2020)
16. Design of Novel Disturbing Peptides Against Ace2 Sars-Cov-2 Spike-Binding Region by Computational Approaches, Frontiers in Pharmacology (2022)
17. Inter-Brct Linker Is Probably the Most Intolerant Region of the Brca1 Brct Domain, Journal of Biomolecular Structure and Dynamics (2023)
18. Factors Involved in the Immunogenicity of Biopharmaceutical Products and Mitigation Strategies, Minerva Biotechnology and Biomolecular Research (2023)
19. Preventing Aggregation of Recombinant Interferon Beta-1B in Solution by Additives: Approach to an Albumin-Free Formulation, Advanced Pharmaceutical Bulletin (2015)
20. The Importance of the Non-Active Site and Non-Periodical Structure Located Histidine Residue Respect to the Structure and Function of Exo-Inulinase, International Journal of Biological Macromolecules (2017)
21. Drug Repurposing for Targeting Fibronectin in Treatment of Endometriosis and Cancers, Journal of Biomolecular Structure and Dynamics (2023)
22. In Silico Designing of Hyper-Glycosylated Analogs for the Human Coagulation Factor Ix, Journal of Molecular Graphics and Modelling (2016)
23. Computational and in Vitro Targeting of Huvecs by Ara-Linker-Tgfαl3 Through Vegfr2, Molecular Simulation (2024)
24. In Silico Studying of the Whole Protein Structure and Dynamics of Dickkopf Family Members Showed That N-Terminal Domain of Dickkopf 2 in Contrary to Other Dickkopfs Facilitates Its Interaction With Low Density Lipoprotein Receptor Related Protein 5/6, Journal of Biomolecular Structure and Dynamics (2019)
25. Computational and Nonglycosylated Systems: A Simpler Approach for Development of Nanosized Pegylated Proteins, Drug Design# Development and Therapy (2016)
26. Optimization of a Recombinant Blar-Ctd Protein Formulation Using the Response Surface Methodology, Journal of Biological Engineering (2024)
27. Immunomodulatory Effects of a Rationally Designed Peptide Mimetic of Human Ifnβ in Eae Model of Multiple Sclerosis, Progress in Neuro-Psychopharmacology and Biological Psychiatry (2018)
28. Next-Generation Version of Recombinant Human Interferon-Beta: A Molecular Dynamic Simulation Study, Informatics in Medicine Unlocked (2022)
29. 3D Printing of Complicated Gelma-Coated Alginate/Tri-Calcium Silicate Scaffold for Accelerated Bone Regeneration, International Journal of Biological Macromolecules (2023)
30. Pierce Into Structural Changes of Interactions Between Mutated Spike Glycoproteins and Ace2 to Evaluate Its Potential Biological and Therapeutic Consequences, International Journal of Peptide Research and Therapeutics (2022)
31. Polycaprolactone/Polyacrylic Acid/Graphene Oxide Composite Nanofibers As a Highly Efficient Sorbent to Remove Lead Toxic Metal From Drinking Water and Apple Juice, Scientific Reports (2024)
32. Design of a Dual-Function Agent by Fusing a Designed Anti-Vegf-A Binder and Cpg-2 Enzyme, Journal of Biomolecular Structure and Dynamics (2023)
33. New Engineered Fusion Peptide With Dual Functionality: Antibacterial and Strong Binding to Hydroxyapatite, International Journal of Peptide Research and Therapeutics (2020)
34. Molecular Interaction of Fibrinogen With Zeolite Nanoparticles, Scientific Reports (2019)
35. Point Mutation Approach to Reduce Antigenicity of Interferon Beta, International Journal of Peptide Research and Therapeutics (2020)
36. Mechanistic Understanding of the Interactions Between Nano-Objects With Different Surface Properties and Α-Synuclein, ACS Nano (2019)
37. Preparation, Characterization, and Molecular Dynamic Simulation of Novel Coenzym Q10 Loaded Nanostructured Lipid Carriers, Current Pharmaceutical Design (2023)
38. Binder Design for Targeting Sars-Cov-2 Spike Protein: An in Silico Perspective, Gene Reports (2022)
39. In Silico and in Vitro Investigation of a Likely Pathway for Anti-Cancerous Effect of Thrombocidin-1 As a Novel Anticancer Peptide, Protein and Peptide Letters (2020)
40. Human Il-2Rα Subunit Binding Modulation of Il-2 Through a Decline in Electrostatic Interactions: A Computational and Experimental Approach, PLoS ONE (2022)