Search results for "binding"
showing 10 items of 3896 documents
Interpretation of Ocular Melanin Drug Binding Assays. Alternatives to the Model of Multiple Classes of Independent Sites
2016
Melanin has a high binding affinity for a wide range of drugs. The determination of the melanin binding capacity and its binding affinity are important, e.g., in the determination of the ocular drug distribution, the prediction of drug effects in the eye, and the trans-scleral drug delivery. The binding parameters estimated from a given data set vary significantly when using different isotherms or different nonlinear fitting methods. In this work, the commonly used bi-Langmuir isotherm, which assumes two classes of independent sites, is confronted with the Sips isotherm. Direct, log-log, and Scatchard plots are used, and the interpretation of the binding curves in the latter is critically a…
Relevance of Multidrug Resistance Proteins on the Clinical Efficacy of Cancer Therapy
2005
Variations in drug uptake and efflux, as well as changes in intracellular drug entrapment and distribution may represent important resistance mechanisms to cancer therapy. A variety of ATP binding cassette transporters (ABC) localised in multiple cell membranes is implied in those phenomena, representing a mechanism of protection of cells against xenobiotics. Many cancer cell lines over express some ABC transporters, especially p-glycoprotein, MRP1 and BCRP. This over expression is related to worse cancer treatment outcome and, in some cases, reduced overall survival of cancer patients. This paper reviews the location and physiological role of the three transporters mentioned and also descr…
Microseparation techniques for the study of the enantioselectivity of drug-plasma protein binding.
2009
Stereoselectivity in protein binding can have a significant effect on the pharmacokinetic and pharmacodynamic properties of chiral drugs. The investigation of enantioselectivity of drugs in their binding with human plasma proteins and the identification of the molecular mechanisms involved in the stereodiscrimination by the proteins represent a great challenge for clinical pharmacology. In this review, the separation techniques used for enantioselective protein binding experiments are described and compared. An overview of studies on enantiomer–protein interactions, enantiomer–enantiomer interactions as well as chiral drug–drug interactions, including allosteric effects, is presented. The c…
Molecular interaction of artemisinin with translationally controlled tumor protein (TCTP) of Plasmodium falciparum
2012
Malaria causes millions of death cases per year. Since Plasmodium falciparum rapidly develops drug resistance, it is of high importance to investigate potential drug targets which may lead to novel rational therapy approaches. Here we report on the interaction of translationally controlled tumor protein of P. falciparum (PfTCTP) with the anti-malarial drug artemisinin. Furthermore, we investigated the crystal structure of PfTCTP. Using mass spectrometry, bioinformatic approaches and surface plasmon resonance spectroscopy, we identified novel binding sites of artemisinin which are in direct neighborhood to amino acids 19-46, 108-134 and 140-163. The regions covered by these residues are know…
Differential interactions of the broad spectrum drugs artemisinin, dihydroartemisinin and artesunate with serum albumin
2013
Artemisinin is a drug, widely used in malaria treatment. As the binding affinity of artemisinin and its derivatives dihydroartemisinin and artesunate to blood serum proteins might influence the effectiveness of the drug, binding of artemisinin and derivatives to serum albumin was studied under near physiological conditions. Binding kinetics indicate a simple, single-step association process for all artemisinin derivatives. The determined changes in enthalpy and entropy upon drug binding clearly indicate that hydrophobic forces are most important for artemisinin and dihydroartemisinin binding, whereas binding of artesunate is governed by both hydrophilic and hydrophobic forces. Key residues,…
Influence of Pigmentation on the Codeine Content of Hair Fibers in Guinea Pigs
1997
Tortoise shell guinea pigs (n = 7) were administered codeine (1 mg/mL codeine-base) in their drinking water for 3 weeks. Black, reddish-brown and white hair was collected separately from each animal before and after treatment. The hair samples were analyzed by GC/MS. The experiment showed positive results for all hair fibers with large individual variability of drug incorporation. Low drug intake resulted in small differences of the drug content in hair fibers different in color, whereas in cases of high drug intake a strong influence of hair pigmentation on the analytical results was observed. The highest drug content was always found in black hair samples, non-pigmented hair showed the lo…
Intracellular retention of ABL kinase inhibitors determines commitment to apoptosis in CML cells
2012
PLoS one 7(7), e40853 (2012). doi:10.1371/journal.pone.0040853
Echovirus 1 Entry into Polarized Caco-2 Cells Depends on Dynamin, Cholesterol, and Cellular Factors Associated with Macropinocytosis
2013
ABSTRACT Enteroviruses invade their hosts by crossing the intestinal epithelium. We have examined the mechanism by which echovirus 1 (EV1) enters polarized intestinal epithelial cells (Caco-2). Virus binds to VLA-2 on the apical cell surface and moves rapidly to early endosomes. Using inhibitory drugs, dominant negative mutants, and small interfering RNAs (siRNAs) to block specific endocytic pathways, we found that virus entry requires dynamin GTPase and membrane cholesterol but is independent of both clathrin- and caveolin-mediated endocytosis. Instead, infection requires factors commonly associated with macropinocytosis, including amiloride-sensitive Na + /H + exchange, protein kinase C, …
Exploring the mass surface near the rare-earth abundance peak via precision mass measurements at JYFLTRAP
2019
The JYFLTRAP double Penning trap at the Ion Guide Isotope Separator On-Line (IGISOL) facility has been used to measure the atomic masses of 13 neutron-rich rare-earth isotopes. Eight of the nuclides, $^{161}$Pm, $^{163}$Sm, $^{164,165}$Eu, $^{167}$Gd, and $^{165,167,168}$Tb, were measured for the first time. The systematics of the mass surface has been studied via one- and two-neutron separation energies as well as neutron pairing-gap and shell-gap energies. The proton-neutron pairing strength has also been investigated. The impact of the new mass values on the astrophysical rapid neutron capture process has been studied. The calculated abundance distribution results in a better agreement w…
EGFL7 ligates αvβ3 integrin to enhance vessel formation
2013
Angiogenesis, defined as blood vessel formation from a preexisting vasculature, is governed by multiple signal cascades including integrin receptors, in particular integrin αVβ3. Here we identify the endothelial cell (EC)-secreted factor epidermal growth factor-like protein 7 (EGFL7) as a novel specific ligand of integrin αVβ3, thus providing mechanistic insight into its proangiogenic actions in vitro and in vivo. Specifically, EGFL7 attaches to the extracellular matrix and by its interaction with integrin αVβ3 increases the motility of EC, which allows EC to move on a sticky underground during vessel remodeling. We provide evidence that the deregulation of EGFL7 in zebrafish embryos leads …