Effects of Isoxazolyl Steroids on Key Genes of Sonic Hedgehog Cascade Expression in Tumor Cells.

Activation of the Hedgehog (Hh) signaling pathway is often associated with the progression of various types of cancer. The purpose of study was to search for inhibitors of the Hh signaling pathway among eight compounds belonging to the group of isoxazolyl steroids. The evaluation of the effectiveness of the compounds was based on the analysis of their cytotoxicity, effect on the cell cycle, on the expression of key Hh-signaling-pathway genes (Ptch1, Smo, and Gli1) and putative target genes MMP-2 and MMP-9.

Blood Plasma Markers in Depressed Mice under Chronic Social Defeat Stress.

It has previously been shown that, in mice, chronic social defeat stress in daily agonistic interactions leads to a depression-like state similar to that in depressive patients. With this model, it has become obvious that it is possible to study peripheral markers of the depression-like state in an experiment. This paper was aimed at searching for protein markers in the blood plasma of depressed mice in the chronic social conflict model, which allows for us to obtain male mice with repeated experiences of defeat.

Protease S of entomopathogenic bacterium Photorhabdus laumondii: expression, purification and effect on greater wax moth Galleria mellonella.

Background: Protease S (PrtS) from Photorhabdus laumondii belongs to the group of protealysin-like proteases (PLPs), which are understudied factors thought to play a role in the interaction of bacteria with other organisms. Since P. laumondii is an insect pathogen and a nematode symbiont, the analysis of the biological functions of PLPs using the PrtS model provides novel data on diverse types of interactions between bacteria and hosts.

T5-like phage BF23 evades host-mediated DNA restriction and methylation.

Bacteriophage BF23 is a close relative of phage T5, a prototypical that infects . BF23 was isolated in the middle of the XXth century and was extensively studied as a model object. Like T5, BF23 carries long ∼9.

Differential Expression of Proteins Associated with Bipolar Disorder as Identified Using the PeptideShaker Software.

The prevalence of bipolar disorder (BD) in modern society is growing rapidly, but due to the lack of paraclinical criteria, its differential diagnosis with other mental disorders is somewhat challenging. In this regard, the relevance of proteomic studies is increasing due to the development of methods for processing large data arrays; this contributes to the discovery of protein patterns of pathological processes and the creation of new methods of diagnosis and treatment. It seems promising to search for proteins involved in the pathogenesis of BD in an easily accessible material-blood serum.

Some structural features of the peptide profile of myelin basic protein-hydrolyzing antibodies in schizophrenic patients.

The antibodies of schizophrenic patients that hydrolyze myelin basic protein (MBP) have been actively studied recently, but the mechanism of the catalytic properties of immunoglobulin molecules remains unknown. Determination of specific immunoglobulin sequences associated with the high activity of MBP proteolysis will help to understand the mechanisms of abzyme catalysis. In the course of comparative mass spectrometric analysis of IgG peptides from the blood serum of patients with acute schizophrenia and healthy people, 12 sequences were identified, which were found only in antibodies that hydrolyze MBP.

Mass Spectrometric Identification of BSA Covalently Captured onto a Chip for Atomic Force Microscopy.

Mass spectrometry (MS) is one of the main techniques for protein identification. Herein, MS has been employed for the identification of bovine serum albumin (BSA), which was covalently immobilized on the surface of a mica chip intended for investigation by atomic force microscopy (AFM). For the immobilization, two different types of crosslinkers have been used: 4-benzoylbenzoic acid N-succinimidyl ester (SuccBB) and dithiobis(succinimidyl propionate) (DSP).

Synthesis and Biological Evaluation of New Isoxazolyl Steroids as Anti-Prostate Cancer Agents.

Steroids with a nitrogen-containing heterocycle in the side chain are known as effective inhibitors of androgen signaling and/or testosterone biosynthesis, thus showing beneficial effects for the treatment of prostate cancer. In this work, a series of 3β-hydroxy-5-ene steroids, containing an isoxazole fragment in their side chain, was synthesized. The key steps included the preparation of Weinreb amide, its conversion to acetylenic ketones, and the 1,2- or 1,4-addition of hydroxylamine, depending on the solvent used.

In vitro interactions of abiraterone, erythromycin, and CYP3A4: implications for drug-drug interactions.

Potential drug-drug interactions of the antitumor drug abiraterone and the macrolide antibiotic erythromycin were studied at the stage of cytochrome P450 3A4 (CYP3A4) biotransformation. Using differential spectroscopy, we have shown that abiraterone is a type II ligand of CYP3A4. The dependence of CYP3A4 spectral changes on the concentration of abiraterone is sigmoidal, which indicates cooperative interactions of CYP3A4 with abiraterone; these interactions were confirmed by molecular docking.

200+ Protein Concentrations in Healthy Human Blood Plasma: Targeted Quantitative SRM SIS Screening of Chromosomes 18, 13, Y, and the Mitochondrial Chromosome Encoded Proteome.

This work continues the series of the quantitative measurements of the proteins encoded by different chromosomes in the blood plasma of a healthy person. Selected Reaction Monitoring with Stable Isotope-labeled peptide Standards (SRM SIS) and a gene-centric approach, which is the basis for the implementation of the international Chromosome-centric Human Proteome Project (C-HPP), were applied for the quantitative measurement of proteins in human blood plasma. Analyses were carried out in the frame of C-HPP for each protein-coding gene of the four human chromosomes: 18, 13, Y, and mitochondrial.

Conjugates of 17-substituted testosterone and epitestosterone with pyropheophorbide a differing in the length of linkers.

Conjugates of 17α-substituted testosterone (1 and 2) and 17β-substituted epitestosterone (3 and 4) with pyropheophorbide a were synthesized. The scheme consisted of synthesis of 17α-hydroxy-3-oxopregn-4-en-21-oic and 17β-hydroxy-3-oxopregn-4-en-21-oic acids, and their coupling with pyropheophorbide a by means of either ethylene diamine, or 1,5-diamino pentane linkers. Mutual influence of steroidal and macrocyclic fragments in conjugates molecules was dependent on configuration of C17 and length of linker, that was established by analysis of H NMR spectra and molecular models of conjugates.

The mechanism of a one-substrate transketolase reaction.

Transketolase catalyzes the transfer of a glycolaldehyde residue from ketose (the donor substrate) to aldose (the acceptor substrate). In the absence of aldose, transketolase catalyzes a one-substrate reaction that involves only ketose. The mechanism of this reaction is unknown.

Targeted Quantitative Screening of Chromosome 18 Encoded Proteome in Plasma Samples of Astronaut Candidates.

This work was aimed at estimating the concentrations of proteins encoded by human chromosome 18 (Chr 18) in plasma samples of 54 healthy male volunteers (aged 20-47). These young persons have been certified by the medical evaluation board as healthy subjects ready for space flight training. Over 260 stable isotope-labeled peptide standards (SIS) were synthesized to perform the measurements of proteins encoded by Chr 18.

Scrutiny of electrochemically-driven electrocatalysis of C-19 steroid 1α-hydroxylase (CYP260A1) from Sorangium cellulosum So ce56.

Direct electrochemistry and bioelectrocatalysis of a newly discovered C-19 steroid 1α-hydroxylase (CYP260A1) from the myxobacterium Sorangium cellulosum So ce56 were investigated. CYP260A1 was immobilized on screen-printed graphite electrodes (SPE) modified with gold nanoparticles, stabilized by didodecyldimethylammonium bromide (SPE/DDAB/Au). Cyclic voltammograms in argon-saturated substrate free 0.

Expression and characterization of a new esterase with GCSAG motif from a permafrost metagenomic library.

As a result of construction and screening of a metagenomic library prepared from a permafrost-derived microcosm, we have isolated a novel gene coding for a putative lipolytic enzyme that belongs to the hormone-sensitive lipase family. It encodes a polypeptide of 343 amino acid residues whose amino acid sequence displays maximum likelihood with uncharacterized proteins from Sphingomonas species. A putative catalytic serine residue of PMGL2 resides in a new variant of a recently discovered GTSAG sequence in which a Thr residue is replaced by a Cys residue (GCSAG).

Lipophilic derivatives of natural chlorins: synthesis, mixed micelles with phospholipids, and uptake by cultured cells.

The chemical synthesis of six lipophilic conjugates of chlorins was carried out, in which lipophilic fragment (either hexadecyl- or cholest-5-en-3β-yloxyethyl-) bound to 13(1)-, 15(2)-, 17(3)-positions of macrocycle by formation of related carboxamides. Structure of synthesized conjugates was studied by spectral methods and molecular modeling. Lipophilic conjugates of chlorins, being mixed with egg yolk phosphatidyl choline, formed mixed micelles stable in aqueous media under physiological conditions.

Synthesis of 21-nitrogen substituted pregna-5,17(20)-dienes from pregnenolone.

The facile synthesis of six [17(20)Z]- and [17(20)E]-isomeric 3β-hydroxy-pregna-5,17(20)-dien-21-oyl amides and three [17(20)E]-3β-hydroxy-2-[prergna-5,17(20)-dien-20-yl]-oxazolines from pregnenolone is presented. The synthetic scheme consists of transformation of pregnenolone into the known 17α-bromo-21-iodo-3β-acetoxypregn-5-en-20-one followed by reaction with ethanolamine, 2-methyl-2-aminopropanol, and (1-aminocyclohexyl)methanol resulted in mixture of [17(20)E]- and [17(20)Z]-pregna-5,17(20)-dien-21-(2-hydroxy)-oyl amides; separation of [17(20)E]- and [17(20)Z]-isomers; their cyclization into [17(20)E]-oxazolines under action of POCl(3) in pyridine, and removal of acetate protecting groups. Significantly different orientation of nitrogen containing substituents in [17(20)Z]- and [17(20)E]-isomers regarding to steroid backbone enables their configuration to be easily identified by NMR spectroscopy.

[17(20)E]- and [17(20)Z]-pregna-5,17(20)-dien-21-oylamides. Facile synthesis and primary evaluation for cancer cells proliferation.

Reaction of 17alpha-bromo-21-iodo-3beta-acetoxypregn-5-en-20-one with ammonia, primary, and secondary amines is simple and convenient method for preparation of [17(20)E]- and [17(20)Z]-pregna-5,17(20)-dien-21-oylamides. Synthesis and characteristics of 12 related amides are presented. Primary testing on cells proliferation indicated differing effects of synthesized compounds on androgen insensitive MCF-7 cells and androgen sensitive LNCaP cells.