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
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
|Author||: Francesco M. Veronese|
|Publisher||: Springer Science & Business Media|
|Release Date||: 2009-12-30|
|ISBN 10||: 3764386797|
|Pages||: 290 pages|
PEGylation technology and key applications are introduced by this topical volume. Basic physical and chemical properties of PEG as basis for altering/improving in vivo behaviour of PEG-conjugates such as increased stability, improved PK/PD, and decreased immunogenicity, are discussed. Furthermore, chemical and enzymatic strategies for the coupling and the conjugate characterization are reported. Following chapters describe approved and marketed PEG-proteins and PEG-oligonucleotides as well as conjugates in various stages of clinical development.
Bioconjugate Techniques, 3rd Edition, is the essential guide to the modification and cross linking of biomolecules for use in research, diagnostics, and therapeutics. It provides highly detailed information on the chemistry, reagent systems, and practical applications for creating labeled or conjugate molecules. It also describes dozens of reactions, with details on hundreds of commercially available reagents and the use of these reagents for modifying or crosslinking peptides and proteins, sugars and polysaccharides, nucleic acids and oligonucleotides, lipids, and synthetic polymers. Offers a one-stop source for proven methods and protocols for synthesizing bioconjugates in the lab Provides step-by-step presentation makes the book an ideal source for researchers who are less familiar with the synthesis of bioconjugates Features full color illustrations Includes a more extensive introduction into the vast field of bioconjugation and one of the most thorough overviews of immobilization chemistry ever presented
This book is devoted to the engineering of protein-based nanostructures and nanomaterials. One key challenge in nanobiotechnology is to be able to exploit the natural repertoire of protein structures and functions to build materials with defined properties at the nanoscale using “bottom-up” strategies. This book addresses in an integrated manner all the critical aspects that need to be understood and considered to design the next generation of nano-bio assemblies. The book covers first the fundamentals of the design and features of the protein building blocks and their self-assembly illustrating some of the most relevant examples of nanostructural design. Finally, the book contains a section dedicated to demonstrated applications of these novel bioinspired nanostructures in different fields from hybrid nanomaterials to regenerative medicine. This book provides a comprehensive updated review of this rapidly evolving field.
An introduction to the state-of-the-art of the diverse self-assembly systems Self-Assembly: From Surfactants to Nanoparticles provides an effective entry for new researchers into this exciting field while also giving the state of the art assessment of the diverse self-assembling systems for those already engaged in this research. Over the last twenty years, self-assembly has emerged as a distinct science/technology field, going well beyond the classical surfactant and block copolymer molecules, and encompassing much larger and complex molecular, biomolecular and nanoparticle systems. Within its ten chapters, each contributed by pioneers of the respective research topics, the book: Discusses the fundamental physical chemical principles that govern the formation and properties of self-assembled systems Describes important experimental techniques to characterize the properties of self-assembled systems, particularly the nature of molecular organization and structure at the nano, meso or micro scales. Provides the first exhaustive accounting of self-assembly derived from various kinds of biomolecules including peptides, DNA and proteins. Outlines methods of synthesis and functionalization of self-assembled nanoparticles and the further self-assembly of the nanoparticles into one, two or three dimensional materials. Explores numerous potential applications of self-assembled structures including nanomedicine applications of drug delivery, imaging, molecular diagnostics and theranostics, and design of materials to specification such as smart responsive materials and self-healing materials. Highlights the unifying as well as contrasting features of self-assembly, as we move from surfactant molecules to nanoparticles. Written for students and academic and industrial scientists and engineers, by pioneers of the research field, Self-Assembly: From Surfactants to Nanoparticles is a comprehensive resource on diverse self-assembly systems, that is simultaneously introductory as well as the state of the art.
Proceedings of an ACS-PMSE Division Symposium held in Orlando, Florida, August 21-25, 1996
|Author||: Caitlin Gayle Decker|
|Release Date||: 2015|
|Pages||: 144 pages|
Protein therapeutics have become essential to the healthcare and pharmaceutical industries since the first recombinant proteins entered the clinic in the 1980s. Modification of proteins with polymers has traditionally been pursued as a means to improve protein stability and enhance pharmacokinetic properties. In addition to these benefits, polymer conjugation can also be utilized to control and modulate protein activity. The first polymer used for protein conjugation was poly(ethylene glycol) (PEG) in 1977. PEG is currently the only FDA-approved polymer for protein conjugation and 10 PEGylated protein drugs are currently on the market. This dissertation offers three modifications to traditional PEGylation, which allow for the modulation of protein activity. In the first example, masking and unmasking the activity of a model protein, lysozyme, was achieved by incorporating both a reducible disulfide linkage between the polymer and the protein as well as incorporating degradable cyclic ketene acetal (CKA) moieties throughout the backbone of a PEG-like polymer (Chapter 2). Specifically 5,6-benzo-2-methylene-1,3-dioxepane and poly(ethylene glycol) methyl ether methacrylate (PEGMA) were copolymerized by reversible addition-fragmentation chain transfer polymerization (RAFT) facilitated by a cysteine-reactive, pyridyl disulfide (PDS) modified chain transfer agent (CTA). Two polymers, a small (Mn GPC = 10.9 kDa) and a large (Mn GPC = 20.9 kDa) PDS-pPEGMA-co-BMDO, were synthesized with reasonable control (dispersities ( ) = 1.34 and 1.71, respectively). The polymers were then conjugated to a thiol-enriched hen egg white lysozyme by disulfide exchange. Conjugation with the 10.9 kDa polymer resulted in a conjugate, which exhibited high initial activity (63%) while the larger conjugate activity was highly attenuated (20%). Lysozyme release from both polymers by reduction of the disulfide linkage and by hydrolytic cleavage, in basic media, of the polymer backbone was visualized by gel electrophoresis. Reduction of the disulfide conjugation linkage with glutathione resulted in an increase in protein activity for both conjugates. In the next example, site-specific chemical dimerization of fibroblast growth factor 2 (FGF2) with a PEG linker, of optimized length, resulted in a FGF2 homodimer with wound healing ability at exceptionally low concentrations (Chapter 3). Homodimers of FGF2 were synthesized through site-specific conjugation to both ends of poly(ethylene glycol) (PEG). FGF2 was conjugated to 2, 6, and 20 kDa vinyl sulfone bis-functionalized PEG, as well as to a small molecule and mono-functionalized PEG controls. The optimal linker length was determined by screening FGF2 dimer-induced proliferation of human dermal fibroblasts (HDF). The inter-cyteine distance was calculated to be approximately 70 A , which is similar in length to a 2 kDa PEG. FGF2-PEG2k-FGF2 induced greater fibroblast proliferation than FGF2 alone, all other dimers, and all monoconjugates, at each concentration tested, with the greatest difference observed at low (0.1 ng/mL) concentration. FGF2-PEG2k-FGF2 further exhibited superior activity compared to FGF2 for both proliferation and migration in human umbilical vein endothelial cells, as well as improved angiogenesis in vitro. Efficacy in an in vivo wound healing model was assessed in diabetic mice. FGF2-PEG2k-FGF2 increased granulation tissue and blood vessel density in the wound bed compared to FGF2. The results suggest that this rationally designed construct may be useful in chronic wound healing. Lastly, a block copolymer capable of noncovalent and releasable conjugation to histidine-6 tagged proteins, consisting of a PEG-based block and a Ni(II) nitriolotriacetic acid (NTA)-based block was synthesized (Chapter 4). The first block was synthesized via RAFT polymerization of a NTA monomer. The resulting polymer was then utilized as a macro-CTA for the polymerization of PEGMA, resulting in a pNTAMA-b-PEGMA, containing 9 NTAMA repeats and 8 PEGMA repeats, with number average molecular weight (Mn) (GPC) = 9.9 kDa and dispersity ( ) = of 4.5. The high dispersity indicates a lack of control, and disproportionation was further confirmed by 1H-NMR. Initial studies indicated that mono-NTA-His6 interactions are not sufficient for protein conjugation, therefore extension of this work towards a multi-valent approach may prove effective in the future.
This volume of Macromolecular Symposia contains papers presented at the 1st International Symposium on "Reactive Polymers in Inhomogeneous Systems, in Melts and at Interfaces" held in Dresden Germany in July 2000. It includes 42 contributions from renowned scientists dealing with topics of current interest in the field of synthesis, characterization and application of reactive and functional polymers. The papers add significantly to the current understanding of the role of reactive polymers in phenomena such as adhesion, colloidal stability, corrosion resistance and biocompatibility - comprehension which is vital for improving the polymer technologies available today and for the development of new applications.
Smart Polymer Catalysts and Tunable Catalysis describes the latest advances in smart polymer catalysts and tunable catalysis. This book will serve as an ideal reference for scientists, students and researchers working in the fields of catalysis, chemical engineering, chemistry, materials science, biotechnology and nanotechnology. Users will find this to be a distinct, systematic and comprehensive body of knowledge on the field with its compilation of essential knowledge and discussions of extensive potential in both social and commercial impacts. Provides a single-source summary of the emerging frontiers in scientific research in smart polymer catalysts and tunable catalysis Includes very well-organized chapters that are illustrated with over 130 illustrations and figures Written by scientists from prestigious universities and industries across the world Edited by veteran researchers in the field of smart polymers and catalysis