Polymer-Protein Conjugates

Polymer-Protein Conjugates: From Pegylation and Beyond helps researchers by offering a unique reference and guide into this fascinating area. Sections cover the challenges surrounding the homogeneity of conjugates, their purity and polymer toxicity on long-term use, and how to deal with the risk of immunogenicity. These discussions help researchers design new projects by taking into account the latest innovations for safe and site selective polymer conjugation to proteins. PEG has been the gold standard and likely will play this role for many years, but alternatives are coming into the market, some of which have already been launched.After five decades of improvements, the ideas in this book are entering into a new era of innovation because of the advances in genetic engineering, biochemistry and a better understanding of the results from clinical use of PEG conjugates in humans.
- Provides an overview on the state-of-the-art of protein polymer conjugation- Presents both the pros and cons of polymer-protein conjugates from the point-of-view of their clinical outcomes- Outlines advantages and potential risks of present technology based on PEG- Offers new alternatives for PEG and new approaches for on site-selective protein modification- Identifies future direction of research in this field

Introduction and General Aspects of the Technology1. Evolution of Polymer Conjugation to proteins2. PEGylated Proteins: A Rational Design for Mitigating Clearance Mechanisms and Altering Biodistribution3. Overcoming barriers for tumor-targeted drug delivery: the power of macromolecular anticancer drugs with the EPR effect and the modulation of vascular physiologyToxicity and Immunogenicity Studies and Clinical Stage Conjugate Products4. PEG-protein conjugates: Non-clinical and clinical toxicity considerations5. Immunological responses to PEGylated proteins: anti-PEG antibodies6. Immunogenicity assessment of PEGylated proteins, Lonquex, a PEGylated G-CSF case study7. PEG-Protein conjugates: regulatory requirements for characterization8. PEGylation of human coagulation factor VIII and other plasma proteins9. Pegvorhyaluronidase Alfa: A PEGylated Recombinant Human Hyaluronidase PH20 for the Treatment of Cancers That Accumulate Hyaluronan10. Challenges in the analytical characterization of PEGylated asparaginasesNovel Site-Selective Methods of Conjugation11. Glycan-targeted PEGylation for selective modification of proteins12. Sialyltransferase mediated glycoPEGylation13. Enzymatic approaches to new protein conjugates14. Site-specific Polymer-protein conjugates by Cys mutation15. Site-specific PEGylation of interferon beta-1b: from bench to clinic16. Protein modification by bis-alkylationAlternative non-PEG polymers and architectures17. In vivo properties of therapeutic bioconjugates composed of proteins and architecturally/functionally complex polymers18. Poly(2-oxazoline)-protein conjugates19. Polysaccharides for protein and peptide conjugation20. Polysialylation of human coagulation factor VIII