Search results for "Protease inhibitor"

Loss of surface fibronectin after infection of cultured cells by HSV-1 and 2

1985

Fibronectin is lost from the surface of HSV infected cells during cell rounding. In order to investigate also the fate of fibronectin during the process of HSV-induced cell-fusion, BHK, Vero as well as primary or secondary rabbit kidney cells were infected with HSV-1 strains producing cell-fusion. By immunofluorescence and immunoelectron microscopy a considerable loss of fibronectin after HSV infection could be demonstrated leaving only irregular clumps of fibronectin containing virus particles on the cell surface. Decrease and disarrangement of fibronectin was similar during cell rounding and cell fusion. Loss of Fibronectin was closely connected with the two types of the cytopathic effect…

ER+-derived breast cancer stem cells reveal a high expression of the serpin protease inhibitor PI-9.

2015

Introduction: Breast cancers (BC) are the major cause of death in women. More than 70% of BCs express high levels of estrogen receptor-α (ERα) and are sustained for their growth by the hormone. Estrogens seem to protect BC cells from apoptosis mediated by immunosurveillance associated with cytotoxic T lymphocytes and NK cells granzyme B release. However, the production of granzyme B inhibitor PI-9 by tumor cells causes a short-circuit in immunosurveillance’s signalling. Although it has been shown the role of PI-9 in BC cells, its presence has not been investigated in tumor stem cells so far. Methods: Cell viability was evaluated by MTT, cell cycle by propidium iodide staining; mRNA and prot…

Twenty Years of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Time to Reevaluate their Toxicity

2011

Twenty years of effective clinical application have consolidated non-nucleoside reverse transcriptase inhibitors (NNRTI) as essential components of the Highly Active Antiretroviral Therapy (HAART) employed in the treatment of Human Immunodeficiency Virus (HIV). However, as the disease has come under control, there has been growing emphasis on the long-term adverse effects induced by this chronic pharmacological therapy. Although traditionally considered to be safe and well-tolerated drugs, there is mounting evidence that associates NNRTI with the onset of cutaneous reactions, neuropsychiatric symptoms, hepatotoxicity, metabolic disturbances and gastrointestinal toxicity. Though the clinical…

Similarities and differences between crystal and enzyme environmental effects on the electron density of drug molecules

2021

Abstract The crystal interaction density is generally assumed to be a suitable measure of the polarization of a low‐molecular weight ligand inside an enzyme, but this approximation has seldomly been tested and has never been quantified before. In this study, we compare the crystal interaction density and the interaction electrostatic potential for a model compound of loxistatin acid (E64c) with those inside cathepsin B, in solution, and in vacuum. We apply QM/MM calculations and experimental quantum crystallography to show that the crystal interaction density is indeed very similar to the enzyme interaction density. Less than 0.1 e are shifted between these two environments in total. Howeve…

Protease inhibitor atazanavir induces leukocyte-endothelial cell interactions in the microvasculature

2008

Synthesis of phosphono dipeptides, inhibitors of cathepsin C

1998

Abstract Phosphono dipeptides containing glycine, glycylglycine or L-alanine at N-termini and racemic phosphonic acid analogues of aromatic amino acids, as well as racemic alicyclic aminophosphonates, exhibit moderate inhibitory activity towards cathepsin C. This activity is probably due to the binding of the phosphonate moiety by a positively charged part of the enzyme which is complementary to the carboxylate part of the synthetic dipeptide products of the enzymatic reaction.

Lipid profile during pregnancy in HIV-infected women

2006

Purpose: We investigated the evolution of serum lipid levels in HIV-infected pregnant women and the potential effect of antiretroviral treatment during pregnancy using data from a national surveillance study. Method: Fasting lipid measurements collected during routine care in pregnancy were used, analyzing longitudinal changes and differences in lipid values at each trimester by protease inhibitors (Pls) and stavudine use. Multivariate analyses were used to control for simultaneous factors potentially leading to hyperlipidemia. Study population included 248 women. Results: Lipid values increased progressively and significantly during pregnancy: mean increases between the first and third tri…

Management of anemia induced by triple therapy in patients with chronic hepatitis C: Challenges, opportunities and recommendations

2013

SummaryThe addition of protease inhibitors, boceprevir or telaprevir, to peginterferon+ribavirin (PegIFN/RBV) increases the frequency as well as the severity, and hence, clinical relevance of anemia, which has now become one of the major complications associated with triple therapy. Most significant factors associated with anemia in patients receiving triple therapy include older age, lower body mass index (BMI), advanced fibrosis, and lower baseline hemoglobin. The variability in inosine triphosphate pyrophosphatase (ITPA) gene, which encodes a protein that hydrolyses inosine triphosphate (ITP), has been identified as an essential genetic factor for anemia both in dual and triple therapy. …

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 …

Selective uptake and degradation of c-Fos and v-Fos by rat liver lysosomes

1996

AbstractThe transcription factor c-Fos is a short-lived protein and calpains and ubiquitin-dependent systems have been proposed to be involved in its degradation. In this report, we consider a lysosomal degradation pathway for c-Fos. Using a cell-free assay, we have found that freshly isolated lysosomes can take up and degrade c-Fos with high efficiency. v-Fos, the oncogenic counterpart of c-Fos, can also be taken up by lysosomes, yet the amount of incorporated protein is much lower. c-Fos uptake is independent of its phosphorylation state but it appears to be regulated by dimerization with differentially phosphorylated forms of c-Jun, while v-Fos escapes this regulation. Moreover, we show …