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Articles 1 - 16 of 16
Full-Text Articles in Polymer Chemistry
Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov
Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov
Doctoral Dissertations
Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …
Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian
Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian
Doctoral Dissertations
The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …
Intracellular Delivery Of Therapeutic Biomolecules Through Versatile Polymer Nanotechnology, David C. Luther
Intracellular Delivery Of Therapeutic Biomolecules Through Versatile Polymer Nanotechnology, David C. Luther
Doctoral Dissertations
Advancing pharmaceutical technology has made it possible to treat diseases once considered ‘undruggable.’ Access to these new pharmaceutical targets is possible thanks to the advent of protein and nucleic acid therapeutics. Responses to the COVID-19 pandemic, as well as cutting-edge treatments for cancer and multiple sclerosis have centered on these biologic therapies, promising even greater value in the future. However, their utility is limited at a cellular level by inability to cross the plasma membrane. Nanocarrier technologies encapsulate therapeutics and facilitate uptake into the cell but are often trapped and degraded in endosomes. Arginine-functionalized gold nanoparticles (Arg-NPs) provide efficient, direct …
Engineering Stimuli-Responsive Polymeric Nanoassemblies: Rational Designs For Intracellular Delivery Of Biologics, Kingshuk Dutta
Engineering Stimuli-Responsive Polymeric Nanoassemblies: Rational Designs For Intracellular Delivery Of Biologics, Kingshuk Dutta
Doctoral Dissertations
Biologic drugs have gained enormous research attention in recent years as reflected by the development of multiple candidates to the clinical pipelines and an increased percentage of FDA approval. This is reasoned by the fact that biologics have been proven to deliver more predictive and promising benefits for many hard-to-cure diseases by ‘drugging the undruggable’ targets. However, the challenges associated with biologic drug development are multi-fold, viz, poor encapsulation efficacy, systemic instability, low cellular internalization and endosomal escape capability. Thus, it is essential to develop new molecular strategies that can not only address the associated drug delivery challenges, but also …
Protein Detection And Structural Characterization By Mass Spectrometry Using Supramolecular Assemblies And Small Molecules, Bo Zhao
Doctoral Dissertations
Mass spectrometry (MS) has played an increasingly prominent role in proteomics and structure biology because it shows superior capabilities in identification, quantification and structural characterization of proteins. To realize its full potential in protein analysis, significant progress has been made in developing innovative techniques and reagents that can couple to MS detection. This dissertation demonstrates the use of polymeric supramolecular assemblies for enhanced protein detection in complex biological mixtures by MS. An amphiphilic random co-polymer scaffold is developed to form functional supramolecular assemblies for protein/ peptide enrichment. The influences of charge density and functional group pKa on host-guest interactions …
Bio-Inspired Polymers That Bind And Deliver Protein Cargo, Nicholas D. Posey
Bio-Inspired Polymers That Bind And Deliver Protein Cargo, Nicholas D. Posey
Doctoral Dissertations
Delivering functional proteins and antibodies into cells can allow researchers to probe the intracellular environment, discover new cellular pathways, and pioneer new therapeutics. However, the entry of exogenous, charged molecules, like proteins, into the cell is usually restricted by the membrane, thereby hindering intracellular delivery. Membrane permeable molecules such as cell penetrating peptides (CPPs) and protein transduction domains (PTDs) can be used to bypass the cell membrane and deliver protein into the cell, but these peptides involve iterative and laborious syntheses and are limited in terms of their chemical diversity. This dissertation work overall focuses on the design and synthesis …
Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund
Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund
Doctoral Dissertations
The plasma membrane is a major obstacle in the development and use of biomacromolecules for intracellular applications. Consequently, proteins with intracellular targets represent an enormous, yet under studied avenue for therapeutics. Extended research has aimed at facilitating intracellular delivery of exogenous proteins using protein transduction domains (PTDs), which allow transport of bioactive molecules into cells. Synthetic polymers, inspired by PTDs, provide a well-controlled platform to vary molecular architecture for structure activity relationship studies. Specifically, this thesis focuses on the use of ring-opening metathesis, a facile and efficient polymerization technique, through which we can vary structural parameters to optimize delivery of …
Light-Harvesting And Light-Responsive Materials For Optoelectronic And Biological Applications, Youngju Bae
Light-Harvesting And Light-Responsive Materials For Optoelectronic And Biological Applications, Youngju Bae
Doctoral Dissertations
In photodynamic therapy, several critical standards are required of photosensitizers including high singlet oxygen quantum yield, biocompatibility in dark, and long term photochemical stability. In addition, current PDT systems lack active targeting strategies to tumor cells, and instead mainly rely on the natural distribution of PS in the body following injection and application of near-infrared light treatment in the tumor region. This thesis describes a series of BODIPY-based molecules that were designed, synthesized and studied as photosensitizers with high singlet oxygen generation capacity through utilizing the heavy atom effect. Additionally, aqueous solubility and active targeting capability were introduced by photosensitizer …
Influence Of Biomimetic Chelating Packaging On Natural Antimicrobial Efficacy, Paul Castrale
Influence Of Biomimetic Chelating Packaging On Natural Antimicrobial Efficacy, Paul Castrale
Masters Theses
The iron chelating molecule, ethylenediaminetetraacetic acid (EDTA) is used in food applications for the preservation of oxidation prone ingredients. Research has suggested that EDTA is also capable of enhancing the antimicrobial effectiveness of various compounds including naturally-derived antimicrobials. With consumer demand for cleaner food labels, there remains an opportunity to introduce new chelating technology to replace synthetically-derived EDTA. Through photographting and chemical conversion, hydroxamic acid ligands were covalently bound to polypropylene films resulting in polypropylene-graft-poly(hydroxamic acid) (PP-g-PHA). The resulting films demonstrated an ability to chelate 64 nmol/cm2 from an iron saturated environment or 163 nmol/cm …
Thiol-Ene Chemistry As An Enabler Of New Polymer Structures And Architectures, Joel M. Sarapas
Thiol-Ene Chemistry As An Enabler Of New Polymer Structures And Architectures, Joel M. Sarapas
Doctoral Dissertations
This dissertation focuses on two distinct projects: the synthesis and design of novel cell penetrating peptides mimics (CPPMs), and the implementation of the thiol-ene click reaction to generate new polymer architectures and chemistries. Guanidinium-rich CPPMs were generated through both ROMP and RAFT polymerizations, allowing for a comparison to be made across polymer backbone chemistries with respect to both siRNA and protein cellular internalization. A particularly effective methacrylate derived block copolymer was able to deliver siRNA to nearly an entire Jurkat T cell population. The thiol-ene reaction was implemented initially within the context of improving material design for solid polymer electrolytes …
Design Of Romp-Based Protein Mimics For Sirna Delivery, Brittany M. Deronde
Design Of Romp-Based Protein Mimics For Sirna Delivery, Brittany M. Deronde
Doctoral Dissertations
Designing delivery agents for therapeutics is an ongoing challenge. As treatments and desired cargoes become more complex, the need for improved delivery vehicles becomes critical. Excellent delivery vehicles must ensure the stability of the cargo, maintain the cargo’s solubility, and promote efficient delivery and release. In order to address these issues, many research groups have looked to nature for design inspiration. Proteins, such as HIV-1 TAT and Antennapedia homeodomain protein, are capable of crossing cellular membranes. However, due to the complexities of their structures, they are synthetically challenging to reproduce in the laboratory setting. Being able to incorporate the key …
Responsive Supramolecular Assemblies Based On Amphiphilic Polymers And Hybrid Materials, Longyu Li
Responsive Supramolecular Assemblies Based On Amphiphilic Polymers And Hybrid Materials, Longyu Li
Doctoral Dissertations
The design and synthesis of responsive supramolecular assemblies are of great interest due to their applications in a variety of areas such as drug delivery and sensing. We have developed a facile method to prepare self-crosslinking disulfide-based nanogels derived from an amphiphilic random copolymer containing a hydrophilic oligo-(ethylene glycol)-based side-chain functionality and a hydrophobic pyridyl disulfide functional group. This thesis first provides a concept of studying the influence of Hofmeister ions on the size and guest encapsulation stability of a polymeric nanogel. The size and core density of nanogel can be fine-tuned through the addition of both chaotropes and kosmotropes …
Physicochemical And Toxicological Assessment Of Antimicrobial Ε-Polylysine-Pectin Complexes, Cynthia L. Lopez Pena
Physicochemical And Toxicological Assessment Of Antimicrobial Ε-Polylysine-Pectin Complexes, Cynthia L. Lopez Pena
Doctoral Dissertations
ε-Polylysine is an appealing FDA-approved, all natural antimicrobial biopolymer effective against a wide range of microorganisms. Its implementation is greatly limited by its strong cationic charge, which has been linked to instability in food systems, perceived astringency and bitterness, and the ability to inhibit lipid digestion. Previous studies have shown that controlled complexation of ε-polylysine with anionic pectin is able to prevent instability and astringency in simplified model food systems, while maintaining the antimicrobial character of polylysine. Isothermal titration calorimetry, micro-electrophoresis, microscopy, and turbidity analyses of the stability of electrostatic pectin-polylysine complexes in the presence of strongly anionic κ-carrageenan, and …
Guanidinium-Rich Romp Polymers Drive Phase, Charge, And Curvature-Specific Interactions With Phospholipid Membranes, Michael T W Lis
Guanidinium-Rich Romp Polymers Drive Phase, Charge, And Curvature-Specific Interactions With Phospholipid Membranes, Michael T W Lis
Doctoral Dissertations
Protein transduction domains (PTDs) and their and their synthetic mimics are short sequences capable of unusually high uptake in cells. Several varieties of these molecules, including the arginine-rich Tat peptide from HIV, have been extensively used as vectors for protein, DNA, and siRNA delivery into cells. Despite the wide-ranging utility of PTDs and their mimics, their uptake mechanism is still under considerable debate. How the molecules are able to cross phospholipid membranes, and what structural components are necessary for optimal activity are poorly understood. This thesis explores how PTDMs interact with phospholipid membrane phase, anionic lipid content and negative Gaussian …
Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres
Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres
Doctoral Dissertations
Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …
Solid State Chemical Reactions And Polymerizations: The Initial Synthesis Of Dna?, Otto Vogl, Frank T. Traceski
Solid State Chemical Reactions And Polymerizations: The Initial Synthesis Of Dna?, Otto Vogl, Frank T. Traceski
Otto Vogl
A Proposal for Covering individual Macromolecules with Macromolecules including a Realistic Chiral Synthesis of Nucleic Acids.