Search results for "Dissociation constant"
showing 10 items of 55 documents
Nature of (C5Me5)2Mo2O5in water–methanol at pH 0–14. On the existence of (C5Me5)MoO2(OH) and (C5Me5)MoO2+: a stopped-flow kinetic analysis
2002
A stopped-flow analysis of compound Cp*2Mo2O5 (Cp* = η5-C5Me5) in 20% MeOH–H2O over the pH range 0–14 has provided the speciation of this molecule as well as the rate and mechanism of interconversion between the various species that are present in solution. The compound is a strong electrolyte in this solvent combination, producing the Cp*MoO2+ and Cp*MoO3− ions in equilibrium with a small amount of Cp*MoO2(OH), the latter attaining ca. 15% relative amount at pH 4. At low pH ( 6. The acid dissociation constant of Cp*MoO2(OH) has been measured directly (pK = 3.65 ± 0.02) while the pK for the protonation equilibrium leading to Cp*MoO3H2+ is estimated as 5. The prevalent pathway at high pH i…
Identification and Characterization of a Single High-Affinity Fatty Acid Binding Site in Human Serum Albumin.
2017
A single high-affinity fatty acid binding site in the important human transport protein serum albumin (HSA) is identified and characterized using an NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl)-C12 fatty acid. This ligand exhibits a 1:1 binding stoichiometry in its HSA complex with high site-specificity. The complex dissociation constant is determined by titration experiments as well as radioactive equilibrium dialysis. Competition experiments with the known HSA-binding drugs warfarin and ibuprofen confirm the new binding site to be different from Sudlow-sites I and II. These binding studies are extended to other albumin binders and fatty acid derivatives. Furthermore an X-ray crystal structure …
The dimer-monomer equilibrium of SARS-CoV-2 main protease is affected by small molecule inhibitors
2021
AbstractThe maturation of coronavirus SARS-CoV-2, which is the etiological agent at the origin of the COVID-19 pandemic, requires a main protease Mpro to cleave the virus-encoded polyproteins. Despite a wealth of experimental information already available, there is wide disagreement about the Mpro monomer-dimer equilibrium dissociation constant. Since the functional unit of Mpro is a homodimer, the detailed knowledge of the thermodynamics of this equilibrium is a key piece of information for possible therapeutic intervention, with small molecules interfering with dimerization being potential broad-spectrum antiviral drug leads. In the present study, we exploit Small Angle X-ray Scattering (…
Multiple steady states and the form of response functions to antigen in a model for the initiation of T cell activation
2017
The aim of this paper is to study the qualitative behaviour predicted by a mathematical model for the initial stage of T-cell activation. The state variables in the model are the concentrations of phosphorylation states of the T-cell receptor (TCR) complex and the phosphatase SHP-1 in the cell. It is shown that these quantities cannot approach zero and that the model possesses more than one positive steady state for certain values of the parameters. It can also exhibit damped oscillations. It is proved that the chemical concentration which represents the degree of activation of the cell, that of the maximally phosphorylated form of the TCR complex, is, in general, a non-monotone function of…
Inhibition of Formation of Rev-RRE Complex by Pyronin Y
1993
The interaction of pyronin Y, an RNA intercalating drug, with the binding of Rev protein from human immunodeficiency virus type 1 (HIV-1) to Rev-responsive element (RRE)-containing env RNA was studied. In gel retardation assays, recombinant Rev protein tightly bound to in vitro transcribed RRE RNA. Nitrocellulose-filter-binding studies revealed a dissociation constant of ≈(1–2) = 10−10M (Pfeifer et al., 1991). Pyronin Y efficiently suppressed formation of the Rev-RRE complex. At a concentration of 1 μg ml−1, complex formation was almost completely inhibited. Electron microscopy showed that Rev oligomerizes in the presence of RRE-containing RNA with the formation of short rod-like structures…
Improving Dissolution Behavior and Oral Absorption of Drugs with pH-Dependent Solubility Using pH Modifiers: A Physiologically Realistic Mass Transpo…
2021
Orally dosed drugs must dissolve in the gastrointestinal (GI) tract before being absorbed through the epithelial cell membrane. In vivo drug dissolution depends on the GI tract's physiological conditions such as pH, residence time, luminal buffers, intestinal motility, and transit and drug properties under fed and fasting conditions (Paixao, P. et al. Mol. Pharm. 2018 and Bermejo, et al. M. Mol. Pharm. 2018). The dissolution of an ionizable drug may benefit from manipulating in vivo variables such as the environmental pH using pH-modifying agents incorporated into the dosage form. A successful example is the use of such agents for dissolution enhancement of BCS class IIb (high-permeability,…
Measuring single small molecule binding via rupture forces of a split aptamer.
2011
The rupture force of a split (bipartite) aptamer that forms binding pockets for adenosine monophosphate (AMP) was measured by atomic force spectroscopy. Changes in the rupture force were observed in the presence of AMP, while this effect was absent when mutant aptamers or inosine were used. Thus, changes in the rupture force were a direct consequence of specific binding of AMP to the split aptamer. The split aptamer concept allowed the detection of nonlabeled AMP and enabled us to determine the dissociation constant on a single-molecule level.
Overexpression of the insulin-like growth factor I receptor in human pheochromocytomas.
2006
In order to determine the role of the IGF-I receptor (IGF-IR) in human pheochromocytomas we have compared the expression of the IGF-IR in normal tissues and in pheochromocytomas with regard to the IGF-IR mRNA levels and ligand binding. By semiquantitative reverse transcription polymerase chain reaction (RT-PCR), the mRNA of the IGF-IR could be detected in all samples of normal adrenomedullary cells (n=13) and pheochromocytomas (n=16). However, pheochromocytomas exhibited 2.8-fold higher mean IGF-IR mRNA levels than normal adrenomedullary cells (2.8±0.5×105 molecules/μg RNA vs 7.8±1.2×105 molecules/μg RNA; P < 0.001). This overexpression of the IGF-IR in pheochromocytomas could be confirm…
Capillary electrokinetic fractionation mass spectrometry (CEkF/MS): Technology setup and application to metabolite fractionation from complex samples…
2014
Capillary electrokinetic fractionation (CEkF) is investigated as a new, simple, and robust approach for semipreparative and analytical sample analysis based on pKa -dependant pH-driven electrophoretic mobility. CEkF was optimized with contactless conductivity detection and conducted with 10 kV reverse voltage for 10 min, then coupled on/at-line to ESI/MS. We propose a semi-empirical model with 14 representative compounds based on the correlation between sample/medium pH regulating the partial charge, the electrokinetic loading of the capillary and intensity (I) of analytes. According to the model, an empirical function (I = f (pH)) could be derived to calculate the acid dissociation constan…
Theoretical Determination of the pK a Values of Betalamic Acid Related to the Free Radical Scavenger Capacity: Comparison Between Empirical and Quant…
2015
Health benefits of dietary phytochemicals have been suggested in recent years. Among 1000s of different compounds, Betalains, which occur in vegetables of the Cariophyllalae order (cactus pear fruits and red beet), have been considered because of reducing power and potential to affect redox-modulated cellular processes. The antioxidant power of Betalains is strictly due to the dissociation rate of the acid moieties present in all the molecules of this family of phytochemicals. Experimentally, only the pK a values of betanin were determined. Recently, it was evidenced it was evidenced as the acid dissociation, at different environmental pHs, affects on its electron-donating capacity, and fur…