Search results for "screening"

Efficient virtual screening using multiple protein conformations described as negative images of the ligand-binding site.

2010

The protein structure-based virtual screening is typically accomplished using a molecular docking procedure. However, docking is a fairly slow process that is limited by the available scoring functions that cannot reliably distinguish between active and inactive ligands. In contrast, the ligand-based screening methods that are based on shape similarity identify the active ligands with high accuracy. Here, we show that the usage of negative images of the ligand-binding site, together with shape comparison tools, which are typically used in ligand-based virtual screening, improve the discrimination of active molecules from inactives. In contrast to ligand-based shape comparison, the negative …

Palladium(II)-Stabilized Pyridine-2-Diazotates: Synthesis, Structural Characterization, and Cytotoxicity Studies

2018

Well-defined diazotates are scarce. Here we report the synthesis of unprecedented homoleptic palladium(II) diazotate complexes. The palladium(II)-mediated nitrosylation of 2-aminopyridines with NaNO2 results in the formation of metal-stabilized diazotates, which were found to be cytotoxic to human ovarian cancer cells.

Synthetic antitumor vaccines containing MUC1 glycopeptides with two immunodominant domains-induction of a strong immune response against breast tumor…

2011

A shot in the arm for cancer treatment: two MUC1 tetanus toxoid vaccines were synthesized and induced a strong immune response in mice. The antibodies elicited by the vaccines show a high selectivity for the tumor cells in mammary carcinoma tissues and also distinguish between tumor tissues at different stages.

Study and identification of new molecular descriptors, finalized to the development of Virtual Screening techniques through the use of deep neural ne…

2022

Cloning of a DNA fragment encoding part of a 70-kDa heat shock protein ofCandida albicans

1995

Immunoscreening of a mycelial expression library with polyclonal antibodies raised against mycelial cell wall resulted in the detection of a cDNA encoding a heat shock protein of Candida albicans. Sequence analysis of a 0.8-kb cDNA subclone, 2M-1, revealed an open reading frame encoding 244 amino acids. Southern blot analysis with this fragment as a probe demonstrated hybridization to C. albicans DNA. Northern analysis showed a substantial increase in 2M RNA expression levels after cells were subjected to heat shock. Western blot analysis with 2M monospecific antibodies recognized a 70-kDa protein which was present in membrane particles and cytosolic fractions.

Inhibition of Eimeria tenella CDK-related kinase 2: From target identification to lead compounds.

2010

Apicomplexan parasites encompass several human- and animal-pathogenic protozoans such as Plasmodium falciparum, Toxoplasma gondii, and Eimeria tenella. E. tenella causes coccidiosis, a disease that afflicts chickens, leading to tremendous economic losses to the global poultry industry. The considerable increase in drug resistance makes it necessary to develop new therapeutic strategies against this parasite. Cyclin-dependent kinases (CDKs) are key molecules in cell-cycle regulation and are therefore prominent target proteins in parasitic diseases. Bioinformatics analysis revealed four potential CDK-like proteins, of which one—E. tenella CDK-related kinase 2 (EtCRK2)—has already been charact…

Rational design of allosteric modulators of the aromatase enzyme: An unprecedented therapeutic strategy to fight breast cancer.

2019

Estrogens play a key role in cellular proliferation of estrogen-receptor-positive (ER+) breast cancers (BCs). Suppression of estrogen production by competitive inhibitors of the enzyme aromatase (AIs) is currently one of the most effective therapies against ER + BC. Yet, the development of acquired resistance, after prolonged treatments with AIs, represents a clinical major concern. Serendipitous findings indicate that aromatase may be non-competitively inhibited by clinically employed drugs and/or industrial chemicals. Here, by performing in silico screening on two putative allosteric sites, molecular dynamics and free energy simulations, supported by enzymatic and cell-based assays, we id…

Prenatal Ultrasound Screening: False Positive Soft Markers May Alter Maternal Representations and Mother-Infant Interaction

2012

Background In up to 5% of pregnancies, ultrasound screening detects a “soft marker” (SM) that places the foetus at risk for a severe abnormality. In most cases, prenatal diagnostic work-up rules out a severe defect. We aimed to study the effects of false positive SM on maternal emotional status, maternal representations of the infant, and mother-infant interaction. Methodology and Principal Findings Utilizing an extreme-case prospective case control design, we selected from a group of 244 women undergoing ultrasound, 19 pregnant women whose foetus had a positive SM screening and a reassuring diagnostic work up, and 19 controls without SM matched for age and education. In the third trimester…

El terrorismo de la seguridad

2003

The Candida albicans pH-regulated KER1 gene encodes a lysine/glutamic-acid-rich plasma-membrane protein that is involved in cell aggregation.

2004

Immunoscreening of aCandida albicanscDNA library with a polyclonal germ-tube-specific antibody (pAb anti-gt) resulted in the isolation of a gene encoding a lysine/glutamic-acid-rich protein, which was consequently designatedKER1. The nucleotide and deduced amino acid sequences of this gene displayed no significant homology with any other known sequence.KER1encodes a 134 kDa lysine (14·5 %)/glutamic acid (16·7 %) protein (Ker1p) that contains two potential transmembrane segments.KER1was expressed in a pH-conditional manner, with maximal expression at alkaline pH and lower expression at pH 4·0, and was regulated byRIM101. A Δker1/Δker1null mutant grew normally but was hyperflocculant under ge…