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Articles 1 - 5 of 5
Full-Text Articles in Organic Chemicals
Protein Allostery Probed By Ligands Across Sites, Virgil A. Woods
Protein Allostery Probed By Ligands Across Sites, Virgil A. Woods
Dissertations, Theses, and Capstone Projects
Allostery is a pervasive regulatory principle throughout biology, yet the structural pathways by which distal inputs alter active‑site chemistry within protein structures remain incompletely defined and exploited. This dissertation uses protein tyrosine phosphatase 1B (PTP1B) as a tractable model to map those pathways with complementary experimental and computational tools. I integrate high‑resolution hydrogen-deuterium exchange mass spectrometry (HDX-MS), room-temperature crystallography, NMR, steady-state kinetics, crystallographic pseudo-ensembles, and machine-learning-guided ligand discovery. The working premise is that regulation reflects redistribution within a conformational ensemble rather than a binary switch. That orthogonal perturbations by small molecules, mutations, and protein partners can be used to both …
Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore
Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore
Master's Theses
Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …
Advancing Small Molecule Therapies For Myotonic Dystrophy Type 1, Sawyer M. Hicks
Advancing Small Molecule Therapies For Myotonic Dystrophy Type 1, Sawyer M. Hicks
Electronic Theses & Dissertations (2024 - present)
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by the expression of expanded CUG (CUGexp) repeat RNA from the myotonic dystrophy protein kinase (DMPK) gene. This CUGexp repeat RNA’s gain-of-function mechanism leads to the sequestration of muscleblind-like (MBNL) proteins, resulting in widespread alternative splicing dysregulation across tissues. Despite significant research, there are currently no approved therapeutics targeting the underlying causes of DM1. This dissertation explores the development and optimization of a novel class of small molecules, Modified Polycyclic Compounds (MPCs), designed to address splicing dysregulation in DM1. MPCs were designed from previously published …
Design And Synthesis Of Small Molecule Drugs For Cns Disorders, Kirsten T. Tolentino
Design And Synthesis Of Small Molecule Drugs For Cns Disorders, Kirsten T. Tolentino
Theses & Dissertations
Dopamine (DA) is an important neurotransmitter for the regulation and long-term function of the central nervous system (CNS). DA binds to Dopamine Receptors (DR) to stimulate or inhibit adenyl cyclase production to further elicit a pharmacological response. DRs were cloned, and it was determined that there are two families separated by their function and five total subtypes distinguished by their amino acid structure. The Dopamine 4 receptor (D4R) is the second least studied subtype but has high expression in the frontal cortex, amygdala, hippocampus, hypothalamus, globus pallidus, substantia nigra pars reticula, and thalamus. Dopamine signaling and transmission, especially in the …
Identification And Structural Characterization Functional Motifs In The Porphyromonas Gingivalis Mfa1 Short Fimbria., Mohammad K. Roky
Identification And Structural Characterization Functional Motifs In The Porphyromonas Gingivalis Mfa1 Short Fimbria., Mohammad K. Roky
Electronic Theses and Dissertations
Porphyromonas gingivalis is a causative agent of periodontal disease, initially colonizes the oral cavity by adhering to commensal streptococci. Adherence requires the interaction of the minor fimbrial protein (Mfa1) of P. gingivalis with streptococcal antigen I/II (Ag I/II). A peptide derived from Ag I/II peptide has been well characterized and shown to significantly reduce P. gingivalis colonization and bone loss in vivo, suggesting that this interaction represents a potential target for therapeutic intervention. However, the functional motifs of Mfa1 involved in the interaction with Ag I/II remain uncharacterized. A series of N- and C-terminal peptide fragments of Mfa1 were …