A5072407615- Antibiotic Resistance in Bacteria
- Macrophage Migration Inhibitory Factor
- Enzyme Structure and Function
- Cholinesterase and Neurodegenerative Diseases
- Antimicrobial Peptides and Activities
- Nuclear Receptors and Signaling
- Salmonella and Campylobacter epidemiology
- Pneumocystis jirovecii pneumonia detection and treatment
- RNA Interference and Gene Delivery
- Biochemical and Molecular Research
- Molecular Sensors and Ion Detection
- Computational Drug Discovery Methods
- Carbohydrate Chemistry and Synthesis
- Bacterial Genetics and Biotechnology
- Neuroscience and Neuropharmacology Research
- Free Radicals and Antioxidants
- Enzyme-mediated dye degradation
- Metal-Catalyzed Oxygenation Mechanisms
- Immune Response and Inflammation
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Pesticide and Herbicide Environmental Studies
- Pharmacological Receptor Mechanisms and Effects
Duke University
2020-2024
Rhodes College
2016-2023
Crescent University
2021
The UDP-3- O -( R -3-hydroxyacyl)- N -acetylglucosamine deacetylase LpxC is an essential enzyme in the biosynthesis of lipid A, outer membrane anchor lipopolysaccharide and lipooligosaccharide Gram-negative bacteria. development LpxC-targeting antibiotics toward clinical therapeutics has been hindered by limited antibiotic profile reported non-hydroxamate inhibitors unexpected cardiovascular toxicity observed certain hydroxamate non–hydroxamate-based inhibitors. Here, we report preclinical...
The UDP-2,3-diacylglucosamine pyrophosphate hydrolase LpxH is an essential lipid A biosynthetic enzyme that conserved in the majority of gram-negative bacteria. It has emerged as attractive novel antibiotic target due to recent discovery LpxH-targeting sulfonyl piperazine compound (referred AZ1) by AstraZeneca. However, molecular details AZ1 inhibition have remained unresolved, stymieing further development this class antibiotics. Here we report crystal structure Klebsiella pneumoniae...
Dopamine is a ubiquitous neurotransmitter essential in the proper functioning of human body. In addition to this critical role, catecholamine core has shown utility as scaffold for numerous drugs and other applications, like metal detection adhesive materials. Substituents at 6-position dopamine’s catechol can modulate its stereoelectronic properties, acidity phenolic hydroxyl groups, overall hydrophobicity molecule. Herein, we report synthesis series four novel dopamine analogues...
Abstract Despite the widespread emergence of multidrug‐resistant nosocomial Gram‐negative bacterial infections and major public health threat it brings, no new class antibiotics for pathogens has been approved over past five decades. Therefore, there is an urgent medical need developing effective novel against by targeting previously unexploited pathways in these bacteria. To fulfill this crucial need, we have investigating a series sulfonyl piperazine compounds LpxH, dimanganese‐containing...
Enterobacterales, a large order of Gram-negative bacteria, including Escherichia coli and Klebsiella pneumoniae, are major causes urinary tract gastrointestinal infections, pneumonia, other diseases in healthcare settings communities. ESBL-producing Enterobacterales carbapenem-resistant can break down commonly used antibiotics, with some strains being resistant to all available antibiotics. This public health threat necessitates the development novel ideally targeting new pathways these...
Dioxygenase enzymes are essential protein catalysts for the breakdown of catecholic rings, structural components plant woody tissue. This powerful chemistry is used in nature to make antibiotics and other bioactive materials or degrade material, but we have a limited understanding breadth depth substrate space these potent catalysts. Here report steady-state pre-steady-state kinetic analysis dopamine derivatives substituted at 6-position as substrates L-DOPA dioxygenase, an that activity...
The UDP-2,3-diacylglucosamine pyrophosphatase, LpxH, is an essential enzyme in the biosynthesis of lipid A, which functions as hydrophobic anchor lipopolysaccharides or lipooligosaccharides outer leaflet membrane Gram-negative bacteria. This conserved majority bacterial pathogens and excellent novel antibiotic target. Here we report development a coupled, nonradioactive colorimetric LpxH assay suitable for high-throughput analysis inhibition screening. Using this new assay, have established...