- |||||||||| Journal: Biosynthesis of the benzylpyrrolidine precursor in anisomycin by a unique ThDP-dependent enzyme. (Pubmed Central) - Sep 12, 2024
Moreover, sequence similarity network (SSN)-based genome neighborhood network (GNN) analyses of AniP suggested the widespread occurrence of the AniP-like-mediated reaction in the biosynthesis of 1 and its analogs, particularly in the assembly of benzylpyrrolidine. These findings not only expand the repertoire of TKs but also provide a potent biocatalyst that could be used for the structural innovation of 1 and its derivatives.
- |||||||||| Synribo (omacetaxine mepesuccinate) / Teva, napabucasin (BBI608) / Sumitomo Pharma
Journal: Quassinoid analogs exert potent antitumor activity via reversible protein biosynthesis inhibition in human colorectal cancer. (Pubmed Central) - May 22, 2023 BOL-resistant (BR) cell lines, HCT116 and HCA7, were equally sensitive to standard CRC therapeutic agents and known STAT3 inhibitors but resistant to homoharringtonine (HHT), a known protein synthesis inhibitor...Of note, BOL did not inhibit protein synthesis in normal human colon epithelial cells whereas HHT and napabucasin remained effective in these normal cells...Treatment with the most potent analog, 5c, resulted in significant inhibition of cell proliferation and protein synthesis at nanomolar concentrations. These quassinoid analogs may represent a novel class of protein synthesis inhibitors for the treatment of human CRC.
- |||||||||| Journal: Cladosporin, A Highly Potent Antimalaria Drug? (Pubmed Central) - May 9, 2023
Due to its exquisite selectivity towards pathogenic parasites, cladosporin has become a very promising lead compound for developing antiparasitic drugs to treat drug-resistant malaria and cryptosporidiosis infections. Here we review the recent research progress of cladosporin covering aspects of the chemical synthesis, biosynthesis, bioactivity, cellular target and structure-activity relationship.
- |||||||||| Journal: Bacillus velezensis TSA32-1 as a Promising Agent for Biocontrol of Plant Pathogenic Fungi. (Pubmed Central) - Oct 28, 2022
We also detected a surfactin synthesis cluster, known as non-ribosomal peptide synthetases, which biosynthesizes the antibacterial substance lipopeptide. Surfactin, and fengycin family compounds, secondary metabolites known as key factors in biological control, also detected B. velezensis TSA32-1 which shows potential as a biocontrol agent for controlling plant pathogens in agriculture.
- |||||||||| Journal: The Inactivation of LPS Biosynthesis Genes in E. coli Cells Leads to Oxidative Stress. (Pubmed Central) - Sep 18, 2022
In "deep rough" mutants, intensive formation of reactive oxygen species was observed, which, along with a lack of reducing agents, such as reactive sulfur species or NADPH, leads to oxidative stress and an increase in the number of dead cells in the population. Within the framework of modern ideas about the role of oxidative stress as a universal mechanism of the bactericidal action of antibiotics, inhibition of the enzymes of ADP-heptose biosynthesis is a promising direction for increasing the effectiveness of existing antibiotics and solving the problem of multidrug resistance.
- |||||||||| MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute
Journal: Limonin stabilises SIRT6 by activating USP10 in cardiac hypertrophy. (Pubmed Central) - Aug 24, 2022 Within the framework of modern ideas about the role of oxidative stress as a universal mechanism of the bactericidal action of antibiotics, inhibition of the enzymes of ADP-heptose biosynthesis is a promising direction for increasing the effectiveness of existing antibiotics and solving the problem of multidrug resistance. Limonin mediates the ubiquitination and degradation of SIRT6 by activating USP10, providing an attractive therapeutic target for cardiac hypertrophy.
- |||||||||| Review, Journal: Ribotoxic Proteins, Known as Inhibitors of Protein Synthesis, from Mushrooms and Other Fungi According to Endo's Fragment Detection. (Pubmed Central) - Jun 30, 2022
This assay is of great importance in the mushroom kingdom, considering the presence of enzymes that are able to hydrolyze phosphodiester bonds (e.g., ribonucleases, ribotoxins and ribotoxin-like proteins) or to remove a specific adenine (rRNA N-glycosylases). Thus, here we used the β-fragment experimentally detected by Endo's assay as a hallmark to revise the literature available on enzymes from mushrooms and other fungi, whose action consists of protein biosynthesis inhibition.
- |||||||||| Journal: Targeting the translational machinery in gastrointestinal stromal tumors (GIST): a new therapeutic vulnerability. (Pubmed Central) - May 20, 2022
Although KIT-mutant GISTs can be effectively treated with tyrosine kinase inhibitors (TKIs), many patients develop resistance to imatinib mesylate (IM) as well as the FDA-approved later-line agents sunitinib, regorafenib and ripretinib...Homoharringtonine (HHT) is a first-in-class inhibitor of protein biosynthesis and is FDA-approved for the treatment of chronic myeloid leukemia (CML) that is resistant to at least two TKIs...The antitumor activity of HHT was confirmed in a GIST xenograft model. Taken together, inhibition of protein biosynthesis is a promising strategy to overcome TKI resistance in GIST.
- |||||||||| MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute
MZB1 Protein Abundance Is Regulated by Cigarette Smoke Dependent Ubiquitination in Lung Epithelial Cells (Area K, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_3254; Our study proves that the ubiquitin-proteasome machinery is involved in the regulation of MZB1 protein abundance via lysine 66. CSE led to rapid degradation of MZB1 protein levels, providing a basis for further exploring the role of MZB1 expression in the pathogenesis of emphysema and COPD.
- |||||||||| Journal: Transcriptomic analysis of formic acid stress response in Saccharomyces cerevisiae. (Pubmed Central) - Jan 27, 2022
In addition, formic acid can also induce sexual reproduction and spore formation. This study through transcriptome analysis has preliminarily reveal the molecular response mechanism of S. cerevisiae to formic acid stress and has provided a basis for further research on methods used to improve the tolerance to cell inhibitors in lignocellulose hydrolysate.
- |||||||||| Journal: Toxicity and membrane perturbation properties of the ribotoxin-like protein Ageritin. (Pubmed Central) - Dec 29, 2021
The collected results indicate that Ageritin can interact with DPPC/DPPS/Chol vesicles, used as a model of cancer cell membranes, and with DPPC/DPPG vesicles, used as a model of bacterial cell membranes, suggesting a selective interaction with anionic lipids. However, a different perturbation of the two model membranes, mediated by cholesterol redistribution, was observed and this might be at the basis of Ageritin selective toxicity towards cancer cells.
- |||||||||| erythromycin / Generic mfg.
Journal: Ribosome-binding and anti-microbial studies of the mycinamicins, 16-membered macrolide antibiotics from Micromonospora griseorubida. (Pubmed Central) - Nov 6, 2021 Most of the macrolides used currently are semi-synthetic erythromycin derivatives, composed of a 14- or 15-membered macrolactone ring...By determining the structures of complexes of the large ribosomal subunit of Deinococcus radiodurans (D50S) with these 16-membered selected macrolides, and performing anti-microbial studies, we identified resistance mechanisms they may overcome. This new information provides important insights toward the rational design of therapeutics that are effective against drug resistant human pathogens.
- |||||||||| Review, Journal: A Path to the Atomic-Resolution Structures of Prokaryotic and Eukaryotic Ribosomes. (Pubmed Central) - Oct 22, 2021
Structural differences between bacterial and eukaryotic ribosomes that determine the differences in their inhibition were established. These and subsequent atomic-resolution structures of the functional ribosome demonstrated for the first time the details of binding of messenger and transport RNAs, which was the first step towards understanding how the ribosome structure ultimately determines its functions.
- |||||||||| erythromycin / Generic mfg.
Journal: Interaction of Chloramphenicol Cationic Peptide Analogues with the Ribosome. (Pubmed Central) - Jul 8, 2021 It was demonstrated using displacement of the fluorescent erythromycin analogue from its complex with ribosomes that the novel peptide analogues of chloramphenicol were able to bind bacterial ribosome; all the designed tripeptide analogues and one of the chloramphenicol amine derivatives containing fragment of the proline-rich antimicrobial peptides exhibited significantly greater affinity to Escherichia coli ribosome than chloramphenicol...In vitro protein biosynthesis inhibition assay revealed, that the RAW-CAM analogue shows activity at the level of chloramphenicol. These data were confirmed by the chemical probing assay, according to which binding pattern of this analogue in the nascent peptide exit tunnel was similar to chloramphenicol.
- |||||||||| dexamethasone / Generic mfg.
Journal: The soybean GmNFY-B1 transcription factor positively regulates flowering in transgenic Arabidopsis. (Pubmed Central) - Jun 2, 2021 Furthermore, GmNFYB1-GR lines were chemically treated with dexamethasone (Dex, synthetic steroid hormone), cycloheximide (Cyc, an inhibitor of protein biosynthesis), and ethanol to examine their effects on different flowering related marker genes...The overexpression of GmNF-YB1 and GmNF-YB1-GR promote flowering through the higher expression of flowering-related genes. Further GmNF-YB1 and its attachment with the GR receptor can regulate its target genes under Dex/Cyc treatment and might act as flowering inducer under LD and SD conditions.
- |||||||||| Clinical, Review, Journal: Resistance-Guided Discovery of Elfamycin Antibiotic Producers with Antigonococcal Activity. (Pubmed Central) - Jun 1, 2021
The antigonococcal activity of phenelfamycin was shown to be the result of inhibition of protein biosynthesis by binding to EF-Tu. These results indicate that a resistance-based approach of identifying elfamycin producers is translatable to other antibiotic classes that can identify new and overlooked antibiotics necessary to address the antibiotic crisis.
- |||||||||| Journal: Semiconducting Polymer Nanomaterials as Near-Infrared Photoactivatable Protherapeutics for Cancer. (Pubmed Central) - Apr 13, 2021
By synergizing PDT with NIR photoactivation of those biological actions, these protherapeutic agents effectively eliminate tumors and even fully inhibit tumor metastasis. This Account highlights the potential of SPNs for construction of versatile NIR photoactivatable protherapeutics to treat cancer at designated times and locations with high therapeutic outcome and precision.
- |||||||||| Journal: Organelles Targeted BODIPY Photocages: Visible-Light Mediated Sub-Cellular Photorelease. (Pubmed Central) - Sep 9, 2020
We further demonstrate that 2, 4-dinitrophenol, a mitochondrial uncoupler, and puromycin, a protein biosynthesis inhibitor, can be selectively photoreleased in mitochondria and ER, respectively, by visible-light-mediated excitation in live cells. We find that not only that photocaging introduces exquisite spatio-temporal specificity to organelle targeting, it additionally leads to higher efficacy of the released bioactive molecule, most probably due to a localized and abrupt release.
- |||||||||| Journal: Influence of cryoprotective agents on protein biosynthesis in Krebs-2 ascites carcinoma and wheat germ cell-free systems. (Pubmed Central) - Aug 24, 2020
MESO, glycerol, ethylene glycol and PEG-400 were established to cause the Mg-dependent inhibition of protein biosynthesis in cell-free system of Krebs-2 ascites carcinoma cells in endogenous matrices and wheat germ ones in exogenous matrices. It has been shown that the mechanism of inhibiting action of CPAs on protein biosynthesis in cell-free systems is related to Mgdependent inhibition of tRNA aminoacylation, which when penetrating MeSO, glycerol and ethylene glycol CPAs are used, has a reversible character, and when PEG-400 being a hardly penetrating CPA is applied it is just partially recovered.
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