Macromolecular Substances Commons^™

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

Second Generation Phenyloxadiazolyl Methyl Sulfones For Thiol-Specific Bioconjugations, Guillaume Dewaele-Le Roi

Dissertations, Theses, and Capstone Projects

The role of antibody-based molecular agents for diagnosis and therapy of cancer has expanded significantly over the past decades. However, most of these constructs are synthesized using traditional bioconjugation methods based on the random ligations between the molecular cargo and lysine residues within the protein. These non-specific approaches can create poorly defined conjugates with suboptimal immunoreactivity and in vivo performance while Site-specific approaches to antibody bioconjugation based on ligations between maleimides and free cysteine residues have long stood as attractive alternatives. Yet the inherent instability of the thiol-maleimide linkage has fueled the search for new, more stable thiol-reactive prosthetic groups. …

Engineered Plga Nanofibers For Drug Delivery, Andrew Mancuso

Dissertations, Theses, and Capstone Projects

Poly-lactic-co-glycolic acid (PLGA) polymers are rapidly gaining momentum as a platform for next-generation drug delivery systems due to their ease and low cost of synthesis, favorable biocompatibility and biodegradability, and lack of toxicity. In particular, the application of drug-loaded PLGA nanofibers directly to a target tissue may represent a promising alternative to traditional routes of drug administration (e.g., oral, injectable) as they offer the potential to greatly improve bioavailability, increase efficacy, and reduce off-target toxicity. Furthermore, the use of such a system may potentially allow for greater flexibility in clinical drug development, by enabling the use of compounds which have …

Succinylated Polyethylenimine Gene Delivery Agents For Enhanced Transfection Efficacy, Md. Nasir Uddin

Theses and Dissertations--Chemistry

Gene therapy aims to treat patients by altering or controlling gene expression. Today, most clinical approaches are viral-based due to their inherent gene delivery activity. However, there is still a significant interest in nonviral alternatives for gene delivery, particularly synthetic lipids and polymers, that do not suffer the immunogenicity, high cost, or mutagenesis concerns of viral vectors. Polymeric vectors are of particular interest due to the ability to further tune the polymer properties through the incorporation of additional functional units such as targeting ligands or shielding domains. Polyethylenimine (PEI), a highly cationic polymer, is often considered a benchmark for polymer-based …

Determining The Link Between Advanced Glycation Endproducts (Ages), Feeding, And Metabolism, Lauren Wimer

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Reactive a-dicarbonyls (a-DC’s), such as methylglyoxal (MGO), are unavoidable metabolites generated during glycolysis that accumulate with age and have been linked with chronic age-related metabolic diseases such as Diabetes Mellitus. Diabetes Mellitus is generally characterized by peripheral neuropathy and sustained hyperglycemia. Chronic hyperglycemia leads to an increase in glycolysis and a downstream increase in reactive a-DC’s. The human body has a natural method of detoxifying these a-DC’s. Glycolytic cells have enzymes which can detoxify a-DC’s, but if overwhelmed, a-DC’s can accumulate and react non-enzymatically with proteins, lipids and DNA to yield a group of molecules called advanced glycation end-products (AGEs). …

Development Of Hyaluronic Acid-Derived Macromolecular Agents For Multimodal Imaging Probes And Nanomedicine, William M. Payne

Theses & Dissertations

Cancer, one of the most challenging maladies facing modern medicine, is a complex family of diseases that requires a multifaceted treatment regime. In recent years, increased research effort has been placed on the development of nanoscale formulations as a potential method to improve therapeutic efficacy and offer better treatment. Both drug formulation and biomedical imaging has benefitted from the development of new, nanoscale agents. Hyaluronic Acid (HA), a naturally occurring glycosaminoglycan, is a promising platform for the development of new drug delivery systems. Furthermore, hyaluronic acid is the principal ligand for the cell surface receptor CD44, which is overexpressed on …

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of …