A practical approach to the synthesis of the A, B and C-ring subunit of cyclopamine has been developed. This synthetic tactic highlights the utility of mandelate acetal-mediated resolution of the fused ring ketone (±)-4 and IBX-mediated oxidation cascades from 12 to 9. The availability of advanced intermediates from enantiomerically pure (+)-4 and 2 could provide efficient access to biologically active and structurally diverse C-nor-D-homo-steroidal alkaloids such as cyclopamine.
Chemistry Techniques, Synthetic ; methods ; Molecular Structure ; Organic Chemistry Phenomena ; Stereoisomerism ; Steroids ; chemistry ; Veratrum Alkaloids ; chemical synthesis ; chemistry

This study was purposed to investigate the effect of phenylhexyl isothiocyanate (PHI) on Wnt/β-catenin signaling pathway, histone acetylation, histone methylation and cell apoptosis in Jurkat cell line. The viability of Jurkat cells after treatment with PHI was tested by MTT. Apoptotic rate of Jurkat cells was measured by flow cytometry. The levels of Wnt/β-catenin related proteins including β-catenin, TCF, c-myc, and cyclinD1, histone acetylated H3 and H4, histone methylated H3K9 and H3K4 were detected by Western blot. The results showed that PHI inhibited the cell growth and induced apoptosis in Jurkat cells in time-and dose-dependent manners. Its IC50 at 48 h was about 20 µmol/L. Expression of histone acetylated H3, H4 and histone methylated H3k4 increased after exposure to PHI for 3 h, while histone methylated H3K9 decreased. Expression of β-catenin was not changed after exposure to PHI for 3 h, but expression of β-catenin, and its cell cycle-related genes such as TCF, c-myc and cyclinD1 decreased after exposure to PHI for 7 h. It is concluded that PHI regulates acetylation and methylation of histone, inhibits Wnt/β-catenin signal pathway, and is able to induce apoptosis and inhibits growth of Jurkat cells.
Acetylation ; Acylation ; Cyclin D1 ; metabolism ; Histones ; metabolism ; Humans ; Isothiocyanates ; pharmacology ; Jurkat Cells ; Methylation ; Proto-Oncogene Proteins c-myc ; metabolism ; TCF Transcription Factors ; metabolism ; Wnt Signaling Pathway ; drug effects ; beta Catenin ; metabolism

Formation of malignant tumor originating from normal healthy cell is a multistep process including genetic and epigenetic lesions. Previous studies of cell line model systems displayed that early important epigenetic events happened in stepwise fashion prior to cell immortalization. Once these epigenetic alterations are integrated into chromatin, they will perform vertical propagation through cell subculture. Hence, status of epigenetics is dramatically important in maintaining of cell identity. Histone modification is another factor of epigenetic alterations during human oncogenesis. Histones, one of main components of chromatin, can be modified post-translationally. Histone tail modifications are regulated by corresponding modification enzymes. This review focuses on the description of relationship between the main sites of histone modification and oncogenesis.
Acetylation ; Carcinogenesis ; Epigenesis, Genetic ; Histones ; metabolism ; Humans ; Methylation ; Phosphorylation

Toxicoproteomics integrates the proteomic knowledge into toxicology by enabling protein quantification in biofluids and tissues, thus taking toxicological research to the next level. Post-translational modification (PTM) alters the three-dimensional (3D) structure of proteins by covalently binding small molecules to them and therefore represents a major protein function diversification mechanism. Because of the crucial roles PTM plays in biological systems, the identification of novel PTMs and study of the role of PTMs are gaining much attention in proteomics research. Of the 300 known PTMs, protein acylation, including lysine formylation, acetylation, propionylation, butyrylation, malonylation, succinylation, and crotonylation, regulates the crucial functions of many eukaryotic proteins involved in cellular metabolism, cell cycle, aging, growth, angiogenesis, and cancer. Here, I reviewed recent studies regarding novel types of lysine acylation, their biological functions, and their applicationsin toxicoproteomics research.
Acetylation ; Acylation ; Aging ; Cell Cycle ; Lysine ; Protein Processing, Post-Translational ; Proteins ; Proteomics ; Toxicology

OBJECTIVETo study the chemical constituents of the leaf of Clausena lansium (Lour.) Skeels.

METHODThe compounds were isolated by various chromatographic techniques and their structures were elucidated by their physicochemical properties and the analysis of their spectroscopic data.

RESULTSeven compounds were isolated and identified as corchoionoside C (1), 1'-O-beta-D-glucopyranosyl (2R,3S)-3-hydroxynodakenetin (2), quercetin-3-O-robinobioside (3), rutin (4), quercetin-3-O-scillabioside (5), keampferol-3-O-alpha-L-rhamnopyranosyl(1-->2) [alpha-L-rhamnopyranosyl(1-->6)]-beta-D-glucopyranoside (6), mauritianin (7).

CONCLUSIONCompounds 1-7 were isolated from the genus Clausena for the first time.

Resistance to the cytotoxic actions of antineoplastic drugs remains a barrier to the establishment of curative chemotherapy regimens for cancer. Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene is the major molecular mechanism enhancing efflux pump for various anticancer agents, hence caused MDR. Transcription factor, DNA methylation, histone acetylation/deacetylation, phosphorylation and glycosylation and MDR1 gene polymorphisms play pivotal role in regulation of P-glycoprotein, and may become new therapeutic targets. This paper summarized the advances of studies on expression and regulation of P-glycoprotein.
ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Acetylation ; DNA Methylation ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Genes, MDR ; Glycosylation ; Humans ; Neoplasms ; metabolism ; pathology ; Phosphorylation ; Polymorphism, Genetic ; Transcription Factors ; genetics ; metabolism

Gata4 is an important transcription factor in heart development. Gata4 post-transcriptional protein modification regulates transcriptional activity and DNA binding, which in turn affects expression of downstream genes and transcription factors, differentiation of embryonic stem cells and cardiogenesis. This article summarizes the effect of post-transcriptional protein modification on transcriptional activity of Gata4 and the relationship between this effect and congenital heart disease. It was shown that acetylation, phosphorylation and SUMOylation upregulate transcriptional activity, DNA binding, downstream gene expression and embryonic stem cell differentiation. On the other hand, methylation and deacetylation downregulate Gata4 transcriptional activity. Post-transcriptional protein modification of Gata4 is very important in clinical research on congenital and other heart diseases.
Acetylation ; Animals ; GATA4 Transcription Factor ; chemistry ; genetics ; metabolism ; Humans ; Methylation ; Phosphorylation ; Protein Processing, Post-Translational ; Sumoylation

Correct diagnosis and successful therapy are extremely important to enjoy a healthy life when suffering from a disease. To achieve these aims, various cutting-edge technologies have been designed and fabricated to diagnose and treat specific diseases. Among these technologies, aptamer–nanomaterial hybrids have received considerable attention from scientists and doctors because they have numerous advantages over other methods, such as good biocompatibility, low immunogenicity and controllable selectivity. In particular, aptamers, oligonucleic acids or peptides that bind to a specific target molecule, are regarded as outstanding biomolecules. In this review, several screening techniques for aptamers, also called systematic evolution of ligands by exponential enrichment (SELEX) methods, are introduced, and diagnostic and therapeutic aptamer applications are also presented. Furthermore, we describe diverse aptamer–nanomaterial conjugate designs and their applications for diagnosis and therapy.
Diagnosis ; Mass Screening ; Peptides ; SELEX Aptamer Technique

AIM: To synthesize the baicalein amino acid derivatives and evaluate their cytotoxicity activities in vitro. METHODS: Amino acids were subjected to methylation and aminoacylation reaction, then reacted with formaldehyde and baicalein to synthesize baicalein-8 benzyl amino acid derivatives. Through carboxyl group protection and aminoacylation of amino acid and benzyl protection of baicalein, derivatives of baicalein-6-O-amino acid esters were obtained. All of the target compounds were identified by IR, MS and (1)H NMR. RESULTS: Thirteen novel derivatives were synthesized and characterized. Their cytotoxic activities were assessed by the MTT method on the inhibition of HepG2 cells in vitro. CONCLUSION Compounds 4c, 4d, 7a and 7b showed a significant increase in cytotoxicity compared with baicalein.
Acylation ; Amino Acids ; chemistry ; Cell Proliferation ; drug effects ; Flavanones ; chemical synthesis ; chemistry ; toxicity ; Hep G2 Cells ; Humans ; Methylation ; Molecular Structure

Proteins exert their roles in life activities via post-translational modifications(PTMs),which include phosphorylation,acetylation,ubiquitination,glycosylation,and methylation.These modifications can change the functions of proteins and play key roles in a variety of diseases.Endometriosis is a common disease in women of childbearing age,although its molecular mechanisms remain unclear.Recent studies have shown that PTMs may be involved in the pathogenesis of endometriosis.Here we review the roles of PTMs in the occurrence and development of endometriosis and the potential medical treatments.
Acetylation ; Endometriosis/pathology* ; Female ; Glycosylation ; Humans ; Phosphorylation ; Protein Processing, Post-Translational ; Ubiquitination