Search results for "binding"
showing 10 items of 3896 documents
Preliminary approach to elucidate the role of pigment as a binding site for drugs and chemicals in anagen hair: differential uptake of 3 H-haloperido…
2002
A striking difference was observed for cellular-bound drug in HaCaT and Sk-Mel-1 cells for a fixed drug exposure time of 72 h and varying 3H-haloperidol concentrations in the culture media. Drug uptake was dependent on drug concentration and linearly correlated for both the non-pigment- and the pigment-producing cells which however was different in magnitude. In an additional investigation the time course of drug uptake during 3H-haloperidol exposure (400 pmol/ml; 28 days) revealed increasing drug concentrations in the Sk-Mel-1 population, whereas drug concentrations in the keratinocytes reached a plateau within a short time period. In contrast to the HaCaT cells no tendency to saturation w…
The cell adhesion domain of type XVII collagen promotes integrin-mediated cell spreading by a novel mechanism.
2001
Type XVII collagen (BP180) is a keratinocyte transmembrane protein that exists as the full-length protein in hemidesmosomes and as a 120-kDa shed ectodomain in the extracellular matrix. The largest collagenous domain of type XVII collagen, COL15, has been described previously as a cell adhesion domain (Tasanen, K., Eble, J. A., Aumailley, M., Schumann, H., Baetge, J, Tu, H., Bruckner, P., and Bruckner-Tuderman, L. (2000) J. Biol. Chem. 275, 3093-3099). In the present work, the integrin binding of triple helical, human recombinant COL15 was tested. Solid phase binding assays using recombinant integrin alpha(1)I, alpha(2)I, and alpha(10)I domains and cell spreading assays with alpha(1)beta(1)…
Potential antipsoriatic effect of chondroitin sulfate through inhibition of NF-κB and STAT3 in human keratinocytes
2012
Abstract Chondroitin sulfate (CS) is a natural glycosaminoglycan, formed by the 1–3 linkage of d -glucuronic acid to N-acetylgalactosamine, present in the extracellular matrix. It is used as a slow acting disease modifying agent in the treatment of osteoarthritis, and part of its beneficial effects are due to its antiinflammatory properties that result from an inhibitory effect on NF-κB signaling pathway. This ability raises the hypothesis that CS might be effective in other chronic inflammatory processes such as psoriasis, in which a deregulation of NF-κB is a key feature. In addition, psoriasis is characterized by an upregulation of STAT3 signaling pathway that is related to the epidermal…
Preliminary approach to elucidate the role of pigment as a binding site for drugs and chemicals in anagen hairs: pigments as carriers for 3 H-haloper…
2002
In view of the melanin-binding characteristics of haloperidol and its differential uptake by pigment- and non-pigment-producing cells, a co-culture of HaCaT with Sk-Mel-1 cell lines was performed to investigate whether melanosomes act as carriers for drug molecules associated with the pigments. Initially, HaCaT and Sk-Mel-1 cells were separately cultivated in the presence of 3H-haloperidol (400 pmol/ml medium ) for 28 days followed by subsequent co-cultivation in the absence of 3H-haloperidol for 5 days. The transfer of pigments into the keratinocytes during co-culture was confirmed by transmission electron microscopy. After the co-culture experiments a striking increase (or = 50%) of 3H-ha…
Resistance of keratinocytes to TGFbeta-mediated growth restriction and apoptosis induction accelerates re-epithelialization in skin wounds.
2002
The pleiotropic growth factor TGFβ plays an important role in regulating responses to skin injury. TGFβ targets many different cell types and is involved in all aspects of wound healing entailing inflammation,re-epithelialization, matrix formation and remodeling. To elucidate the role of TGFβ signal transduction in keratinocytes during cutaneous wound healing, we have used transgenic mice expressing a dominant negative type II TGFβ receptor exclusively in keratinocytes. We could demonstrate that this loss of TGFβ signaling in keratinocytes led to an accelerated re-epithelialization of full thickness excisional wounds accompanied by an increased proliferation in keratinocytes at the wound ed…
Inhibition Mechanism of SARS‐CoV‐2 Main Protease with Ketone‐Based Inhibitors Unveiled by Multiscale Simulations: Insights for Improved Designs**
2021
Abstract We present the results of classical and QM/MM simulations for the inhibition of SARS‐CoV‐2 3CL protease by a hydroxymethylketone inhibitor, PF‐00835231. In the noncovalent complex the carbonyl oxygen atom of the warhead is placed in the oxyanion hole formed by residues 143 to 145, while P1–P3 groups are accommodated in the active site with interactions similar to those observed for the peptide substrate. According to alchemical free energy calculations, the P1′ hydroxymethyl group also contributes to the binding free energy. Covalent inhibition of the enzyme is triggered by the proton transfer from Cys145 to His41. This step is followed by the nucleophilic attack of the Sγ atom on …
Thermal aggregation of bovine serum albumin at different pH: comparison with human serum albumin.
2007
We report here a study on thermal aggregation of BSA at two different pH values selected to be close to the isoelectric point (pI) of this protein. Our aim is to better understand the several steps and mechanisms accompanying the aggregation process. For this purpose we have performed kinetics of integrated intensity emission of intrinsic and extrinsic dyes, tryptophans and ANS respectively, kinetics of Rayleigh scattering and of turbidity. The results confirm the important role played by conformational changes in the tertiary structure, especially in the exposure of internal hydrophobic regions that promote intermolecular interactions. We also confirm that the absence of electrostatic repu…
The Expanding Spectrum of Mutations in Hereditary Angioedema.
2021
The evolution in the knowledge of rare genetic diseases such as hereditary angioedema (HAE) has increased at a parallel pace with the development of new molecular tools. The deficiency of C1 inhibitor (C1-INH) has been recognized as the main cause of HAE (HAE-C1-INH) since the 1960s, but the discovery of the wide spectrum of mutations affecting the C1-INH gene (SERPING1) was possible only from the late 1980s, when Sanger sequencing became available and more accessible worldwide. Nevertheless, the involvement of other genes in HAE was discovered only in 2006 with the description of mutations in the F12 gene in patients with HAE and normal C1-INH. In the last 3 years, advanced next-generation…
Identification of an endothelial cell binding site on kininogen domain D3
1995
High and low molecular mass kininogen, two multidomain plasma proteins, bind to endothelial cells, platelets, and neutrophils in the intravascular compartment. The specific cell attachment site on their common heavy chain is mediated by domain-3, a cystatin-like structure with inhibitory capacity for papain-like proteinases (Jiang, Y., Müller-Esterl, W., and Schmaier, A. H. (1992) J. Biol. Chem. 267, 3712-3717). In this report, the domain-3 cell binding site is determined by an antibody-directed strategy. The epitope of monoclonal antibody HKH15, which binds to domain-3 and blocks the binding of kininogens to platelets and endothelial cells, was mapped using seven synthetic peptides, which …