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

Plant serine carboxypeptidase-like acyltransferases (SCPL-AT) have similar structural characteristics and high homology compared to the serine carboxypeptidase. They can transfer the acyl from acyl glucose esters to many natural products, participate in the acylation modification of plant secondary metabolites, enrich the structural diversity of natural products, and improve the physicochemical properties such as water solubility and stability of compounds. This review summarizes the structural characteristics, catalytic mechanism, functional characterization, and biocatalytic applications of SCPL-AT from plants. This will help to promote the functional characterization of these acyltransferase genes and the biosynthesis of useful plant secondary metabolites by synthetic biotechnology.
Acylation ; Acyltransferases/metabolism* ; Carboxypeptidases/metabolism* ; Plants/enzymology*

Quercetin 3-O-glycosides (Q3Gs) are important members of quercetin glycosides with excellent pharmacological activities such as anti-oxidation, anti-inflammation, anti-cancer and anti-virus. Two representatives of Q3Gs, rutin and troxerutin, have been developed into clinical drugs, demonstrating Q3Gs have become one of the important sources of innovative drugs. However, the applications of Q3Gs in food and pharmaceutical industries are hampered by its poor bioavailability. Of the known means, selective acylation modification of Q3Gs through enzymatic catalysis to obtain Q3G esters is one of the effective ways to improve its bioavailability. Herein, the enzyme-mediated acylation of Q3Gs were reviewed in details, focusing on the four tool enzymes (acyltransferases, lipases, proteases and esterases) and the whole-cell mediated biotransformation, as well as the effect of acylations on the biological activities of Q3Gs. Furthermore, the highly efficient synthesis and diversification of acylated site for Q3G esters were also discussed. Taken together, this review provides a new perspective for further structural modifications of Q3Gs towards drug development.
Acylation ; Biological Availability ; Glycosides ; Quercetin ; Rutin

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

PURPOSE: Idoxifene is currently entering phase II clinical trials for the treatment of advanced breast cancer. The radiolabeled idoxifene using 123I provides an opportunity for clinical pharmacology with single photon emission computed tomography (SPECT). The purpose of this study was to prepare radiolabeled idoxifene using 123I and to determine its cell uptake of breast cancer cell line. MATERIALS AND METHODS: With a view to evaluating new anticancer drugs, we are investigating the novel antiestrogen pyrrolidino- 4-iodotamoxifen (idoxifene). [123I]Idoxifene has been prepared in no-carrier-added form using a tributyl stannylated precursor which has been synthesized by means of (2-chloroethoxy)benzene with (+/-)-2- phenylbutanoic acid on the basis of previously reported standard methods. The biodistribution and dynamic behavior of the compound were investigated using the comparative breast cancer cell line, MCF-7 (estrogen receptor-positive) and MDA-MB-468 (non-estrogen receptor). RESULTS AND CONCLUSION: Acylation of (2-chloroethoxy)benzene with (+/-)-2-phenylbutanoic acid gave the versatile ketone (81%) which reacted with 1,4-diiodobenzene to give triphenylethylene as a mixture of E and Z geometric isomers, which were separated by the recrystallization in ethanol. The E-isomer was treated with pyrrolidine to give idoxifene (67%). In order to incorporate radioactive iodine into the 4-position, the 4-stannylated precursor was prepared (30%). The yield of radioiodination was 90-92% with a high radiochemical purity greater than 98%. The ratio of tumor uptake of the breast cancer cell line between MCF-7 and MDA-MB-468 was about 1.7.
Acylation ; Breast Neoplasms* ; Breast* ; Cell Line ; Estrogen Receptor Modulators ; Ethanol ; Iodine ; Pharmacology, Clinical ; Tomography, Emission-Computed, Single-Photon

Spiramycin and midecamycin are 16-membered macrolide antibiotics with very similar chemical structures. Spiramycin has three components, namely spiramycin I, II and III. Spiramycin II and III are, respectively, the O-acetyl and propionyl derivatives at C3-hydroxyl group of spiramycin I. Midecamycin has four components, and the C3-hydroxyl group of midecamycin is all O-propionylated. The enzyme adding acyl group(s) at the C3-hydroxyl group during the biosynthesis of spiramycin and midecamycin is 3-O-acyltransferase. The 3-O-acyltransferases for spiramycin and midecamycin are also very similar, and presume to function when exchanged. To explore whether the 3-O-acyltransferase for midecamycin biosynthesis hold still the character of selective and efficient propionylation for spiramycin I at its C3-hydroxyl group, we inserted mdmB, the 3-O-acyltransferase gene from Streptomyces mycarofaciens ATCC 21454 for midecamycin biosynthesis, into a mutant strain of S. spiramyceticus F21, in which the 3-O-acyltransferase gene for spiramycin biosynthesis, sspA, was deleted; and the mdmB was integrated exactly into the chromosomal site where the sspA was deleted. We name this "hybrid" strain as SP-mdmB. HPLC analysis of the spiramycin produced by SP-mdmB showed that spiramycin I was still the major component, although the relative proportions of both spiramycin II and III increased significantly. We thus conclude that MdmB from Streptomyces mycarofaciens ATCC 21454 for midecamyicn biosynthesis do not hold the character of selective and efficient propionylation for spiramycin I within S. spiramyceticus F21, and this character is possibly limited in Streptomyces mycarofaciens ATCC 21454 for midecamycin biosynthesis.
Acylation ; Acyltransferases ; genetics ; metabolism ; Culture Media ; Genes, Bacterial ; Genetic Engineering ; methods ; Leucomycins ; biosynthesis ; Spiramycin ; biosynthesis ; Streptomyces ; enzymology ; genetics ; Substrate Specificity

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

It was found that psoralen derivative could perform a Friedel-Crafts acylation smoothly with acetic anhydride to give 5'-acetylpsoralen in a 73% yield. In the presence of boron trifluoride etherate, 5'-acetylpsoralen reacted with both aromatic amines and aliphatic amine smoothly to afford 5'-Schiff-base group substituted psoralen derivatives in 72%-92% yields. The novel synthetic method has the advantages of cheap materials, mild reaction conditions, good yields and high regioselectivity in the Friedel-Crafts acylation. Cell viability assay by MTT demonstrates that some of the psoralen derivatives 6 have antiproliferative activities.
Acylation ; Boranes ; chemistry ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Furocoumarins ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Schiff Bases ; chemistry

Even though chemistry is now in place that potentially allows high coupling efficiencies to be attained, successful coupling is usually a challenge when so-called "difficult sequences" is encountered in peptide synthesis. Some factors that affect the coupling efficiency have been discussed and related methods to overcome those obstacles have been introduced in present review. All suggestions proposed here are valuable and also feasible to improve the coupling completeness in both liquid-phase or solid-phase
Acylation ; Amino Acid Sequence ; Molecular Structure ; Organophosphorus Compounds ; chemistry ; Peptide Fragments ; chemical synthesis ; chemistry ; Peptides ; chemical synthesis ; chemistry ; Proline ; analogs & derivatives ; chemistry ; Resins, Synthetic ; chemistry ; Temperature ; Thiazoles ; chemistry ; Thiocyanates ; chemistry ; Triazoles ; chemistry

In vitro transcription systems with T7 RNA polymerase (T7 RNAP) were widely used in preparation of RNA because of their simplicity and high efficiency. The transcripts would have additional 5' sequence since T7 promoter spans the transcription start site, while deletion of the transcription start site would severely reduce the T7 RNAP transcriptional activity. We successfully developed an in vitro transcription by combining of T7 RNAP high efficient transcription system and highly specific self-splicing technology of ribozymes, in this system, ribozyme self-splices at the designed specific site and releases the aim RNA without affecting transcription efficiency of T7 RNAP, the aminoacylation activity of human mitochondrial tRNA(Trp) (HmtRNA(Trp) (UCA)) is 113.6 pmol/microg. This method with its high efficiency on transcription and good repeatability is very suitable for preparation of accurate RNA in large scale.
Base Sequence ; DNA-Directed RNA Polymerases ; genetics ; Humans ; Molecular Sequence Data ; RNA ; genetics ; RNA Splicing ; RNA, Catalytic ; genetics ; RNA, Transfer, Trp ; genetics ; Transcription, Genetic ; Transfer RNA Aminoacylation ; genetics ; Viral Proteins ; genetics