Now showing items 2051-2060 of 2090
Optimization of Acidic Post-translational Modification Detection and Natural Product Biosynthetic Enzyme Analysis with Dual Polarity nLC/FT-ICR Mass Spectrometry
(2017)
Mass spectrometry-based proteomic protocols can identify thousands of expressed proteins with widely varying concentrations. However, acidic post-translational modifications (PTMs), e.g., phosphorylation and sulfation, are ...
Understanding the Roles of Metal Ions in the Fate of Reactive Oxygen Species and in Alzheimer’s Disease.
(2012)
Biologically relevant metal ions play crucial roles in metabolic regulation and cellular function throughout nature and in the human body. An important regulatory mechanism is control of reactive oxygen species (ROS). The ...
High Throughput Experimentation Facilitated Development of Amine-Acid Cross Coupling Reactions
(2023)
High throughput experimentation (HTE) is an important technique which can expedite the hit-to-lead process in drug discovery. The first chapter of this thesis reviews reported applications using HTE in medicinal chemistry ...
Mechanistic and Structural Insights into the Chemical Modulation of Amyloid Aggregation
(2016)
The aggregation of amyloid-beta (Abeta) is implicated in the etiology of Alzheimer’s disease (AD). Aggregation in vivo permits interactions with transition metal ions and lipids of the cell membrane. Abeta-metal interactions ...
Investigation of Atypical Transformations During the Biosynthesis of Marine Cyanobacterial Natural Products.
(2013)
Naturally occurring chemicals isolated from plants and fungi have been used as medicines for millennia. Biochemical and genetic analysis of these chemically fertile organisms has led to the elucidation of protein-megasynthases ...
Characterization of the Membrane-Bound Full-Length Complex between Cytochrome b5 and Cytochrome P450 2B4.
(2013)
While cyt b5 has been shown to be an essential part of the catalytic cycle of cyt P450 in vivo, very little is known about its membrane-bound full-length structure and its ability to form complexes with cyt P450 in the ...
Inhibition of Nucleotide and One-Carbon Metabolism for the Treatment of Cancer
(2021)
Metabolic reprogramming in cancer was first described in the early to mid-1900s and later labeled as a hallmark. Rapidly proliferating cells require sufficient concentrations of nucleotides and other biomass precursor ...
Structure-Based Design, Synthesis and Evaluation of Novel and Selective Small-Molecule Inhibitors of the Anti-Apoptotic Protein Mcl-1.
(2014)
The mitochondrial pathway to apoptosis is regulated through the protein-protein interactions of pro- and anti-apoptotic members of Bcl-2 family proteins. Overexpression of the anti-apoptotic members such as Mcl-1, Bcl-2 ...
Harnessing Cascade Biocatalysis for the Chemoenzymatic Synthesis of Unnatural Hapalindole-Type Metabolites and Further Exploration into their Biosynthesis
(2022)
This thesis presents results focused on the exploration of the enzymes responsible for the biosynthesis of the hapalindole-type metabolites. Hapalindole-type metabolites are a diverse group of indole alkaloids defined by ...
Development, Synthesis, and Characterization of G Protein-Coupled Receptor Kinase Inhibitors Using Structure Based Drug Design for the Advancement of Heart Failure Therapeutics
(2017)
In heart failure, the β-adrenergic receptors (βARs) become desensitized and uncoupled from heterotrimeric G proteins. This process is initiated by G protein-coupled receptor kinases (GRKs), some of which are upregulated ...