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Polymer Protein Conjugates

Polymer Protein Conjugates Book
Author : Gianfranco Pasut,Samuel Zalipsky
Publisher : Unknown
Release : 2019-11
ISBN : 9780444640819
Language : En, Es, Fr & De

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Book Description :

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

Polymer Protein Conjugates Book
Author : Gianfranco Pasut,Samuel Zalipsky
Publisher : Elsevier
Release : 2019-10-30
ISBN : 0444640827
Language : En, Es, Fr & De

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Book Description :

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

Bioresponsive Polymer protein Conjugates as a Unimolecular Drug Delivery System

Bioresponsive Polymer protein Conjugates as a Unimolecular Drug Delivery System Book
Author : Helena Rosalind Petra Gilbert
Publisher : Unknown
Release : 2007
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Bioresponsive Polymer protein Conjugates as a Unimolecular Drug Delivery System book written by Helena Rosalind Petra Gilbert, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Synthetic Polymer protein Conjugates for Therapeutics

Synthetic Polymer protein Conjugates for Therapeutics Book
Author : Samantha B. McRae
Publisher : Unknown
Release : 2008
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Synthetic Polymer protein Conjugates for Therapeutics book written by Samantha B. McRae, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Novel Precursors for Polymer Protein Conjugate Synthesis Via Reversible Addition Fragmentation Chain Transfer Polymerization

Novel Precursors for Polymer Protein Conjugate Synthesis Via Reversible Addition Fragmentation Chain Transfer Polymerization Book
Author : Christine Maria Schilli
Publisher : Unknown
Release : 2003
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Novel Precursors for Polymer Protein Conjugate Synthesis Via Reversible Addition Fragmentation Chain Transfer Polymerization book written by Christine Maria Schilli, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Design and Synthesis of Sulfonated Polymers for the Preparation of Polymer protein Conjugates with Improved Therapeutic Abilities and Mechanistic Studies

Design and Synthesis of Sulfonated Polymers for the Preparation of Polymer protein Conjugates with Improved Therapeutic Abilities and Mechanistic Studies Book
Author : Andrew Joseph McGahran
Publisher : Unknown
Release : 2013
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

In the first part of this thesis is described the use of free radical polymerization to synthesize a variety of sulfonated polymers. These polymers were employed in a biological screening study to determine their ability to participate in binding of basic fibroblast growth factor to its cellular receptor. Preliminary data suggests that poly(sodium vinyl sulfonate) (pVS) best serves this role. In order to obtain end-functionalized polymers with narrow molecular weight distribution profiles, controlled polymerizations of this monomer using reversible addition-fragmentation chain transfer (RAFT) were attempted. In addition, RAFT polymerization was used to synthesize poly(poly(ethylene glycol methyl ether acrylate)) (pPEGA) and poly(sodium styrene sulfonate)-co-poly(poly(ethylene glycol methacrylate)) (pSS-co-PEGMA). In the second part of this thesis, attempts to prepare fluorescent protein-polymer conjugates for use in biological mechanism studies are described. To achieve this, post-polymerization modification and fluorescent chain transfer agent (CTA) methodologies were employed to install a fluorescent tags onto these polymers.

Protein polymer Conjugate Arrays for Enhanced Biosensor Sensitivity and Selectivity

Protein polymer Conjugate Arrays for Enhanced Biosensor Sensitivity and Selectivity Book
Author : Justin Michael Paloni
Publisher : Unknown
Release : 2020
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The capability of biosensors to provide highly sensitive and selective molecular detection has enabled development of rapid, inexpensive medical diagnostics. Despite significant advancements in sensor design over the past several decades, most biosensors experience significantly reduced sensitivity in common sensing fluids such as blood and urine. In these mixtures, off-target molecules nonspecifically bind to the sensor surfaces, blocking analyte binding sites and increasing background signal. The self-assembled structure of protein-polymer conjugates presents a potential solution to this issue, offering both biological functionality and a mechanism for excluding many non-analyte molecules in biosensing fluids. Therefore, this thesis explores the use of protein-polymer conjugate thin films as biosensors to minimize nonspecific binding effects during detection in complex mixtures. The first part of this thesis focuses on protein engineering methods to improve the self-assembly of protein-polymer conjugates. It is first demonstrated that oligomerization of low-molecular weight protein blocks significantly enhances ordering quality of the corresponding conjugates. As the degree of oligomerization of the protein block increases, conjugates form ordered phases that display longer-range assembly. Another technique shown to improve protein-polymer conjugate self-assembly is fusion of complementary coiled-coil sequences to the protein block. When proteins bearing these sequences are mixed together in solution, a strongly associative coiled-coil forms, promoting a substantial ordering improvement. Both protein oligomerization and fusion to coiled-coil sequences retain the biological functionality of the protein block, and it is found that protein activity generally scales with conjugate ordering quality. The second part of this thesis explores the capabilities of the polymer block in protein-polymer conjugate thin films to control diffusion into these films. By increasing the molecular weight of this polymer block, larger analyte molecules experience less restricted diffusion into the thin films. Transport studies performed in solutions of the polymer block indicate that most proteins display size-based diffusion following the Stokes-Einstein equation, but some proteins deviate significantly from this behavior due to a combination of protein-protein and protein-polymer interactions. When an analyte molecule is mixed with a protein that diffuses faster than the analyte in these polymer solutions, the sensitivity of the thin film conjugate biosensors towards the analyte is often significantly enhanced. This sensitivity improvement is also observed during detection in mixtures containing the analyte and several proteins, only some of which diffuse faster than the analyte. Accordingly, biosensing measurements using protein-polymer conjugate thin films performed in blood serum and urine solutions, which should contain a variety of proteins that diffuse faster than a given analyte, display a two order of magnitude improvement in sensitivity over traditional surface-based biosensor technologies. Thus, protein-polymer conjugate thin film biosensors can overcome nonspecific binding effects and demonstrate greater sensitivity during measurements performed in complex protein mixtures.

Modulating Protein Activity Through Polymer Conjugation

Modulating Protein Activity Through Polymer Conjugation Book
Author : Caitlin Gayle Decker
Publisher : Unknown
Release : 2015
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

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.

Polymer Therapeutics II

Polymer Therapeutics II Book
Author : Ronit Satchi-Fainaro,Ruth Duncan
Publisher : Springer Science & Business Media
Release : 2006-01-12
ISBN : 9783540292111
Language : En, Es, Fr & De

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Book Description :

With contributions by numerous experts

PEGylated Protein Drugs Basic Science and Clinical Applications

PEGylated Protein Drugs  Basic Science and Clinical Applications Book
Author : Francesco M. Veronese
Publisher : Springer Science & Business Media
Release : 2009-12-30
ISBN : 3764386797
Language : En, Es, Fr & De

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Book Description :

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.

Bio synthetic Polymer Conjugates

Bio synthetic Polymer Conjugates Book
Author : Helmut Schlaad
Publisher : Springer
Release : 2012-12-15
ISBN : 3642343503
Language : En, Es, Fr & De

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Book Description :

Polypeptide-Polymer Conjugates, by Henning Menzel Chemical Strategies for the Synthesis of Protein-Polymer Conjugates, by Björn Jung and Patrick Theato Glycopolymer Conjugates, by Ahmed M. Eissa and Neil R. Cameron DNA-Polymer Conjugates: From Synthesis, Through Complex Formation and Self-assembly to Applications, by Dawid Kedracki, Ilyès Safir, Nidhi Gour, Kien Xuan Ngo and Corinne Vebert-Nardin Synthesis of Terpene-Based Polymers, by Junpeng Zhao and Helmut Schlaad

Synthesis of Protein polymer Conjugates for Targeted Drug Delivery

Synthesis of Protein polymer Conjugates for Targeted Drug Delivery Book
Author : Analia Jazmin Vazquez Cegla
Publisher : Unknown
Release : 2018
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Synthesis of Protein polymer Conjugates for Targeted Drug Delivery book written by Analia Jazmin Vazquez Cegla, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Peptide and Protein Drug Delivery

Peptide and Protein Drug Delivery Book
Author : Vincent Lee
Publisher : CRC Press
Release : 1990-11-19
ISBN : 9780824778965
Language : En, Es, Fr & De

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Book Description :

This reference/text covers fundamentals of peptide and protein drug delivery, including such considerations as synthesis, physical chemistry and biochemistry, analysis, proteolytic and transport constraints, pharmacokinetics, and pharmacodynamics; bioavailability from routes of administration, detai

Thiol X Chemistries in Polymer and Materials Science

Thiol X Chemistries in Polymer and Materials Science Book
Author : Andrew B Lowe,Christopher N Bowman
Publisher : Royal Society of Chemistry
Release : 2013-08-13
ISBN : 1849736960
Language : En, Es, Fr & De

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Book Description :

Thiol-X chemistries are already well established techniques, but it is only recently that they have been exploited for the functionalization and synthesis of polymers and other materials. As such, information on these techniques is scattered across the literature and Thiol-X Chemistries in Polymer and Materials Science is the first book to compile work specifically focussing on the application of thiol-based chemistries in materials design and synthesis. The book introduces the various thiol-X chemistries currently available and applications where they have been successfully used, including examples of 'click' processes, in polymerizations, polymer synthesis, and polymer modification. Short 'how to' sections within the chapters also provide general experimental techniques to employ the various chemistries described. Written by leading experts in the field, this book is a comprehensive resource for postgraduates, academics and industrial practitioners interested in polymer and materials applications.

Polymers and Protein conjugates for Tissue Engineering

Polymers and Protein conjugates for Tissue Engineering Book
Author : Sigrid Drotleff
Publisher : Unknown
Release : 2006
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Polymers and Protein conjugates for Tissue Engineering book written by Sigrid Drotleff, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Functionalized Polymers

Functionalized Polymers Book
Author : Narendra Pal Singh Chauhan
Publisher : CRC Press
Release : 2021-05-14
ISBN : 1000291170
Language : En, Es, Fr & De

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Book Description :

Functionalized polymers are macromolecules to which chemically bound functional groups are attached which can be used as catalysts, reagents, protective groups, etc. Functionalized polymers have low cost, ease of processing and attractive features for functional organic molecules. Chemical reactions for the introduction of functional groups in polymers and the conversion of functional groups in polymers depend on different properties. Such properties are of great importance for functionalization reactions for possible applications of reactive polymers. This book deals with the synthesis and design of various functional polymers, the modification of preformed polymer backbones and their various applications.

Concise Encyclopedia of Biomedical Polymers and Polymeric Biomaterials

Concise Encyclopedia of Biomedical Polymers and Polymeric Biomaterials Book
Author : Munmaya Mishra
Publisher : CRC Press
Release : 2017-08-16
ISBN : 1351653032
Language : En, Es, Fr & De

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Book Description :

The Concise Encyclopedia of Biomedical Polymers and Polymeric Biomaterials presents new and selected content from the 11-volume Biomedical Polymers and Polymeric Biomaterials Encyclopedia. The carefully culled content includes groundbreaking work from the earlier published work as well as exclusive online material added since its publication in print. A diverse and global team of renowned scientists provide cutting edge information concerning polymers and polymeric biomaterials. Acknowledging the evolving nature of the field, the encyclopedia also features newly added content in areas such as tissue engineering, tissue repair and reconstruction, and biomimetic materials.

Silicon Versus Carbon

Silicon Versus Carbon Book
Author : Yuri Magarshak,Sergey Kozyrev,Ashok K. Vaseashta
Publisher : Springer Science & Business Media
Release : 2009-05-21
ISBN : 9048125235
Language : En, Es, Fr & De

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Book Description :

Even though there is no generally accepted definition of nanotechnologies to be defined as distinct discipline there is an emerging consensus that their advent and development is a growing in importance factor of the contemporary and future technological civilization. One of these most fundamental issues we are confronted with is the compatibility with life itself. From single cell organisms to humans, carbon is a key building block of all molecular structures of life. In contrast the man created electronic industry to build on other elements, of which silicon is the most common. Both carbon and silicon create molecular chains, although different in their internal structure. All life is built from carbon-based chains. As long as the man built technological products do not directly interfere with the physiology of life the associated risks from them are relatively easy to identify. They are primarily in the environmental pollution and the possibility of upsetting the natural balance of biocoenosis, on a planetary scale. The basic life functions are still not directly subverted. We can use TV, computers, drive cars and use other technological utilities without fear of direct interference with our cellular functions. This is in particular because all these technological utilities are many orders of magnitude larger than typical scales of biological activity. Most of biological activity, from fermentative catalysis to DNA replication takes place on nanoscale. The situation is radically different when the technological goals are building nanoscale size products. All biological processes take place on nanoscale.