A5090832190- Polyamine Metabolism and Applications
- Amino Acid Enzymes and Metabolism
- Cannabis and Cannabinoid Research
- Epigenetics and DNA Methylation
- Synthesis and Biological Evaluation
- Chemical Synthesis and Analysis
- Organophosphorus compounds synthesis
- Insect and Pesticide Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Cancer-related gene regulation
- HIV/AIDS drug development and treatment
- Viral Infections and Vectors
- RNA modifications and cancer
- Antimicrobial Peptides and Activities
- Insect symbiosis and bacterial influences
- Biochemical and Molecular Research
- Carbohydrate Chemistry and Synthesis
- Photochromic and Fluorescence Chemistry
- Metabolism and Genetic Disorders
- Energy and Environment Impacts
- Nicotinic Acetylcholine Receptors Study
- Inorganic Fluorides and Related Compounds
- Synthesis and Reactions of Organic Compounds
- Protein Hydrolysis and Bioactive Peptides
- Phenothiazines and Benzothiazines Synthesis and Activities
Engelhardt Institute of Molecular Biology
2015-2024
Russian Academy of Sciences
2009-2013
Abstract Snyder–Robinson syndrome (SRS) results from mutations in spermine synthase (SMS), which converts the polyamine spermidine into spermine. Affecting primarily males, common manifestations of SRS include intellectual disability, osteoporosis, hypotonia, and seizures. Symptom management is only treatment. Reduced SMS activity causes accumulation while levels are reduced. The resulting exaggerated spermidine:spermine ratio a biochemical hallmark that tends to correlate with symptom...
S-Adenosyl-l-methionine (SAM)-mediated methylation of biomolecules controls their function and regulates numerous vital intracellular processes. Analogs SAM with a reporter group in place the S-methyl are widely used to study these However, many analogs chemically unstable that largely limits practical application. We have developed new compound, SAM-PH , which contains an H-phosphinic (-P(O)(H)OH) instead carboxylic group. SAM-P H is significantly more stable than SAM, retains functional...
The ubiquitous polyamine spermidine is indispensable for eukaryotic growth and cell proliferation. A conserved vital function of across eukaryotes conferred by its aminobutyl group that transferred to a single lysine in translation factor eIF5A form the essential hypusine post-translational modification required cellular translation. In direct contrast, although absolutely α-proteobacterial plant pathogen Agrobacterium tumefaciens, we have found, employing suite natural polyamines synthetic...
The biogenic polyamines, spermine, spermidine (Spd) and putrescine (Put) are present at micro-millimolar concentrations in eukaryotic prokaryotic cells (many prokaryotes have no spermine), participating the regulation of cellular proliferation differentiation. In mammalian Put is formed exclusively from L-ornithine by ornithine decarboxylase (ODC) many potent ODC inhibitors known. bacteria, plants, fungi synthesized also agmatine, which L-arginine arginine (ADC). Here we demonstrate that...
Polyamine metabolism is an attractive anticancer drug target, since polyamines are absolutely required for cellular proliferation, and increased levels of their biosynthetic enzyme ornithine decarboxylase (ODC) associated with cancer. Triethylenetetramine (TETA) a charge-deficient isosteric analogue the polyamine spermidine (Spd) Cu(II)-chelating compound used treatment Wilson's disease, it has been implicated as potential therapeutic drug. In present study, we studied effects TETA in...
The fast spread of bacteria that are resistant to many classes antibiotics (multidrug resistant) is a global threat human and animal health with worrisome scenario ahead. Novel therapeutical strategies crucial importance combat this phenomenon. For purpose, we investigated the antimicrobial properties naturally occurring tripeptide Bialaphos dipeptide L-leucyl-L-phosphinoithricin, synthesis diastereomers separation which herein described. We demonstrate these compounds effective on clinical...
Viruses require host cell metabolites to productively infect, and the mechanisms by which viruses usurp these molecules are diverse. One group of cellular important in virus infection is polyamines, small positively charged involved cycle, translation, nucleic acid metabolism, among other functions. Polyamines support replication diverse viruses, they for processes such as transcription, viral protein enzymatic activity. Rift Valley fever (RVFV) a negative ambisense RNA that requires...
The polyamines are organic polycations present at millimolar concentrations in eukaryotic cells where they participate the regulation of vital cellular functions including proliferation and differentiation. Biological evaluation rationally designed polyamine analogs is one cornerstones research. Here we have synthesized characterized novel C-methylated spermidine analogs, that is, 2-methylspermidine, 3-methylspermidine, 8-methylspermidine. 3-Methylspermidine was found to be metabolically...
Eukaryotic translation initiation factor 5A (eIF5A) is essential for cell proliferation, becoming functionally active only after post-translational conversion of a specific Lys to hypusine [N(ε)-(4-amino-2-hydroxybutyl)lysine]. Deoxyhypusine synthase (DHS) the rate-limiting enzyme this two-step process, and polyamine spermidine natural donor butylamine group reaction, which very conserved-hypusine biosynthesis suffers last when intracellular pool depleted. DHS has strict substrate...
Snyder–Robinson syndrome (SRS) is an X-linked intellectual disability caused by a loss-of-function mutation in the spermine synthase (SMS) gene. Primarily affecting males, main manifestations of SRS include osteoporosis, hypotonic stature, seizures, cognitive impairment, and developmental delay. Because there no cure for SRS, treatment plans focus on alleviating symptoms rather than targeting underlying causes. Biochemically, cells individuals with accumulate excess spermidine, whereas...
The polyamines, spermine (Spm) and spermidine (Spd), are important for cell growth function. Their homeostasis is strictly controlled, a key downregulator of the polyamine pool polyamine-inducible protein, antizyme 1 (OAZ1). OAZ1 inhibits uptake targets ornithine decarboxylase (ODC), rate-limiting enzyme biosynthesis, proteasomal degradation. Here we report, first time, that polyamines induce dimerization mouse recombinant full-length OAZ1, forming an (OAZ1)2-Polyamine complex. Dimerization...
Abstract Enzymatic methyltransferase reactions are of crucial importance for cell metabolism. S -Adenosyl- L -methionine (AdoMet) is a main donor the methyl group. DNA, RNA, proteins, and low-molecular-weight compounds substrates methyltransferases. In mammals, DNA Dnmt3a de novo methylates C5 position cytosine residues in CpG sequences DNA. The methylation pattern one factors that determine epigenetic regulation gene expression. Here, interactions with catalytic domain was first time...
New antibiotics are unquestionably needed to fight the emergence and spread of multidrug-resistant bacteria. To date, targeting bacterial central metabolism have been poorly investigated. By determining minimal inhibitory concentration (MIC) desmethylphosphinothricin (Glu-γ-PH), an analogue glutamate with a phosphinic moiety replacing γ-carboxyl group, we previously showed its promising antibacterial activity on Escherichia coli. Herein, synthetized determined growth inhibition exerted E....
The biogenic polyamines, spermine (Spm) and spermidine, are organic polycations present in millimolar concentrations all eukaryotic cells participating the regulation of vital cellular functions including proliferation differentiation. design biochemical evaluation polyamine analogues cornerstones research. Here we synthesized studied novel C-methylated Spm analogues: 2,11-dimethylspermine (2,11-Me2Spm), 3,10-dimethylspermine (3,10-Me2Spm), 2-methylspermine, 2,2-dimethylspermine. tested...
Homeostasis of the biogenic polyamines spermine (Spm) and spermidine (Spd), present in μM-mM concentrations all eukaryotic cells, is precisely regulated by coordinated activities enzymes polyamine synthesis, degradation, transport, order to sustain normal cell growth viability. Spermine oxidase (SMOX) key most recently discovered enzyme metabolism that plays an essential role regulating homeostasis catalyzing back-conversion Spm Spd. The development many types epithelial cancer associated...