A5007835171- Enzyme function and inhibition
- Chemical Reactions and Mechanisms
- Synthesis and Catalytic Reactions
- Phenothiazines and Benzothiazines Synthesis and Activities
- Erythrocyte Function and Pathophysiology
- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Synthesis and Biological Evaluation
- High Altitude and Hypoxia
- Blood donation and transfusion practices
- Sphingolipid Metabolism and Signaling
- Polysaccharides and Plant Cell Walls
- Zeolite Catalysis and Synthesis
- Chemical Reaction Mechanisms
- Asthma and respiratory diseases
- Sepsis Diagnosis and Treatment
- Catalytic Processes in Materials Science
- Nitric Oxide and Endothelin Effects
- Hemoglobinopathies and Related Disorders
- Clusterin in disease pathology
- Amino Acid Enzymes and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Heart Rate Variability and Autonomic Control
- Mesoporous Materials and Catalysis
- Cardiac, Anesthesia and Surgical Outcomes
Washington University in St. Louis
2017-2023
Vilnius University
2013-2018
Amsterdam UMC Location University of Amsterdam
2014
Human carbonic anhydrase IX (CA IX) is highly expressed in tumor tissues, and its selective inhibition provides a potential target for the treatment of numerous cancers. Development potent, inhibitors against this remains an unmet need anticancer therapeutics. A series fluorinated benzenesulfonamides with substituents on benzene ring was designed synthesized. Several these exhibited potent profile CA IX. Three fluorine atoms significantly increased affinity by withdrawing electrons lowering...
Neuroinflammation, a major hallmark of Alzheimer's disease and several other neurological psychiatric disorders, is often associated with dysregulated cholesterol metabolism. Relative to homeostatic microglia, activated microglia express higher levels Ch25h, an enzyme that hydroxylates produce 25-hydroxycholesterol (25HC). 25HC oxysterol interesting immune roles stemming from its ability regulate Since astrocytes synthesize in the brain transport it cells via ApoE-containing lipoproteins, we...
Substituted tri- and tetrafluorobenzenesulfonamides were designed, synthesized, evaluated as high-affinity isoform-selective carbonic anhydrase (CA) inhibitors. Their binding affinities for recombinant human CA I, II, VA, VI, VII, XII, XIII catalytic domains determined by fluorescent thermal shift assay, isothermal titration calorimetry, a stopped-flow CO2 hydration assay. Variation of the substituents at 2-, 3-, 4-positions yielded compounds with broad range isoform selectivities. Several...
During storage, red blood cells (RBCs) undergo significant biochemical and morphologic changes, referred to collectively as the "storage lesion". It was hypothesized that these defects may arise from disrupted oxygen-based regulation of RBC energy metabolism, with resultant depowering intrinsic antioxidant systems.As a function storage duration, dynamic range in metabolic response three models oxidant stress (methylene blue, hypoxanthine/xanthine oxidase, diamide) assessed, comparing...
The goal of rational drug design is to understand structure-thermodynamics correlations in order predict the chemical structure a that would exhibit excellent affinity and selectivity for target protein. In this study we explored contribution added functionalities benzenesulfonamide inhibitors intrinsic binding affinity, enthalpy, entropy recombinant human carbonic anhydrases (CA) CA I, II, VII, IX, XII, XIII. enthalpies compounds possessing similar structures affinities were found be very...
Intact red blood cells (RBCs) are required for phenotypic analyses. In order to allow separation (time and location) between subject encounter sample analysis, we developed a research-specific RBC cryopreservation protocol assessed its impact on data fidelity key biochemical physiological assays. RBCs drawn from healthy volunteers were aliquotted immediate analysis or following glycerol-based cryopreservation, thawing, deglycerolization. phenotype was by (1) scanning electron microscopy...
Human carbonic anhydrases comprise a family of isoforms that form structurally similar active site and thus it is difficult to design inhibitors would selectively inhibit the targeted isoform leave uninhibited all remaining ones. Most common are aromatic sulfonamides strongly bind CAs, but usually with limited selectivity towards isoform. However, sometimes seemingly minor changes in inhibitor structure may cause significant increase or decrease affinity CA Here, affinities previously...
BACKGROUND We set out to define the impact of collection, processing, and storage on plasma product microparticle (MP) abundance, potential for nitric oxide (NO) scavenging, vasoactivity. STUDY DESIGN AND METHODS Three currently US licensed products were tested: liquid (LP), fresh frozen (FFP), solvent detergent (SDP), along with a under development, spray‐dried (SD‐SDP) with/without beads. Vasoactivity was assessed in vitro using rabbit aortic vascular rings; MP abundance determined by flow...
Membrane reshaping resides at the core of many important cellular processes, and among its mediators are BAR (Bin, Amphiphysin, Rvs) domain-containing proteins. We have explored diversity function Rvs proteins in Candida albicans identified a novel family member, Rvs167-3 (orf19.1861). show that specifically interacts with Rvs162 to form stable heterodimer able bind liposomes vitro. A second, distinct is formed by canonical Rvs161 Rvs167. Purified Rvs161/Rvs167 complex also binds liposomes,...
Rationale Inhaled nitric oxide (NO) exerts a variety of effects through metabolites and these play an important role in regulation hemodynamics the body. A detailed investigation into generation has been overlooked. Objectives We investigated kinetics nitrite S-nitrosothiol-hemoglobin (SNO-Hb) plasma derived from inhaled NO subjects how this modifies cutaneous microvascular response. Findings enrolled 15 healthy volunteers. Plasma levels at baseline during inhalation (15 minutes 40 ppm) were...
ABSTRACT Neuroinflammation is a major hallmark of Alzheimer’s disease and several other neurological psychiatric disorders often associated with dysregulated cholesterol metabolism. Relative to homeostatic microglia, activated microglia express higher levels Ch25h , an enzyme that hydroxylates produce 25-hydroxycholesterol (25HC). 25HC oxysterol interesting immune roles stemming from its ability regulate biosynthesis. Since astrocytes synthesize in the brain transport it cells via...
The clinical syndrome of paraplegia following acute occlusion the infrarenal aorta may be caused by either ischemic spinal cord damage or ischemia cauda equina and sacral nerve roots ganglia. neurologic manifestations are similar therefore specific anatomic diagnosis is difficult. From October 1972 to February 1975 a total 31 patients with aortic were treated at Medizinische Hochschule in Hannover. In nine cases up renal arteries was acute. Three these presented beside on both legs lower...