A5021033761- Monoclonal and Polyclonal Antibodies Research
- Advanced Biosensing Techniques and Applications
- Biosensors and Analytical Detection
- Protein purification and stability
- Advanced biosensing and bioanalysis techniques
- Antibiotic Resistance in Bacteria
- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Microfluidic and Capillary Electrophoresis Applications
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Lipoproteins and Cardiovascular Health
- RNA and protein synthesis mechanisms
- Listeria monocytogenes in Food Safety
- Vibrio bacteria research studies
- Peptidase Inhibition and Analysis
- Plasmonic and Surface Plasmon Research
- Force Microscopy Techniques and Applications
- Molecular Junctions and Nanostructures
- 14-3-3 protein interactions
- Cell death mechanisms and regulation
- Computational Drug Discovery Methods
- Melanoma and MAPK Pathways
- Drug Transport and Resistance Mechanisms
- Protein Structure and Dynamics
Beaumont Hospital
2024
Dublin City University
1999-2022
Cellular Biomedicine Group (United States)
2021
Michael & Associates
2012
Teledyne FLIR (United States)
2011
Stanger Hospital
2006
Texas Instruments (United States)
2002-2003
University of Ulster
1980
ABSTRACT The outer membrane is an essential structural component of Gram-negative bacteria that composed lipoproteins, lipopolysaccharides, phospholipids, and integral β-barrel proteins. A dedicated machinery, called the Lol system, ensures proper trafficking lipoproteins from inner to membrane. LolCDE ABC transporter component, which for bacterial viability. Here, we report a novel pyrrolopyrimidinedione compound, G0507, was identified in phenotypic screen inhibitors Escherichia coli growth...
The Ras-RAF-MEK-ERK signaling axis, commonly mutated in human cancers, is highly regulated to prevent aberrant healthy cells. One of the pathway modulators, 14–3–3, a constitutive dimer, induces RAF dimerization and activation by binding phosphorylated motif C-terminal kinase domain. Recent work has suggested that "DTS" region BRAF necessary for this 14–3–3-mediated activation. We show catalytic activity ATP affinity BRAF:14–3–3 complex insensitive presence or absence DTS, while sites both...
With recent advances and success in several drugs designed to treat acute chronic diseases, targeted covalent inhibitors show a resurgence drug discovery. As inhibition is time-dependent, the preferred quantitative potency metric of irreversible second-order rate constant kinact/Ki, rather than IC50. Here, we present development mass spectrometry-based platform for rapid kinetic analysis inhibitors. Using simple liquid handling robot automated sample preparation solid-phase extraction-based...
The von Hippel–Lindau (VHL) protein plays a pivotal role in regulating the hypoxic stress response and has been extensively studied utilized targeted degradation field, particularly context of bivalent degraders. In this study, we present comprehensive peptidomimetic structure–activity relationship (SAR) approach, combined with cellular NanoBRET target engagement assays to enhance existing VHL ligands. Through systematic modifications molecule, identified 1,2,3-triazole group as an optimal...
Background: Divarasib, a covalent inhibitor targeting the Kirsten rat sarcoma virus oncogene homologue glycine-to-cysteine mutation at position 12 (KRAS G12C), is currently in clinical development for Non Small Cell Lung Cancer (NSCLC) treatment, with various combination partners, such as Src homology region 2 domain-containing phosphatase-2 (SHP2) migoprotafib. A quantitative systems pharmacology (QSP) model essential to quantitatively assess single-agent and pharmacodynamic (PD) effects...
Developing small-molecule (SM) therapeutics that target membrane proteins (MPs) is often challenging, because few biophysical methods can handle the detergents required to maintain stability. Here, we report a surface plasmon resonance (SPR)-based methodology enables characterization of interactions between SMs and an ion channel receptor (MP1) in complex with stabilizing antibody fragment (Fab) surfactant. Briefly, stable MP1-Fab was formed by coimmobilizing MP1 anti-MP1-Fab within hydrogel...
Achieving sufficient pathway suppression for low-abundance cytokines like VEGF may require depletion to femtomolar concentrations using high-affinity antagonists. Understanding the kinetics of this pharmacodynamically complex process is important development anti-VEGF therapeutic molecules Ranibizumab and requires experimental determination kinetic binding constants VEGF-antagonist complex. These measurements are challenging due extremely high affinities, long residence times, a need mimic...
In label-free biomolecular interaction analysis, a standard injection provides an of uniform analyte concentration. An alternative approach exploiting Taylor dispersion produces continuous titration allowing full dose response to be recorded in single injection. The enhanced biophysical characterization that is possible with this new technique demonstrated using commercially available surface plasmon resonance-based biosensor. A kinetic model was fitted locally curves for estimation the...
Necroptotic cell death is promoted by the dimerization-dependent activation of kinase RIPK3.