A5005592180- Microbial Natural Products and Biosynthesis
- Bacteriophages and microbial interactions
- Antimicrobial Peptides and Activities
- Cholinesterase and Neurodegenerative Diseases
- Pesticide Exposure and Toxicity
- Carbohydrate Chemistry and Synthesis
- Chemical Synthesis and Analysis
- Probiotics and Fermented Foods
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- RNA and protein synthesis mechanisms
- Biochemical and Structural Characterization
- Computational Drug Discovery Methods
- Nanowire Synthesis and Applications
- Biochemical and Molecular Research
- Gut microbiota and health
- Calcium signaling and nucleotide metabolism
- Pesticide and Herbicide Environmental Studies
- Genomics and Phylogenetic Studies
- Innovative Microfluidic and Catalytic Techniques Innovation
- vaccines and immunoinformatics approaches
- Erythrocyte Function and Pathophysiology
- Immunotherapy and Immune Responses
- Marine Sponges and Natural Products
- Cell Image Analysis Techniques
Institute of Bioorganic Chemistry
2015-2024
Institute of Bioorganic Chemistry
2018-2024
Lomonosov Moscow State University
2017-2023
Moscow State University
2023
Significance Biocompatible microfluidic double water-in-oil-in-water emulsion (MDE) enables in-droplet cultivation of different living species. The combination droplet-generating machinery with FACS followed by next-generation sequencing and liquid chromatography-mass spectrometry analysis the secretomes encapsulated organisms yielded detailed genotype/phenotype descriptions. MDE–FACS platform we developed enabled highly sensitive single-cell selection predesigned activity exploration...
Microbiome spectra serve as critical clues to elucidate the evolutionary biology pathways, potential pathologies, and even behavioral patterns of host organisms. Furthermore, exotic sources microbiota represent an unexplored niche discover microbial secondary metabolites. However, establishing bacterial functionality is complicated by intricate web interactions inside microbiome. Here we apply ultrahigh-throughput (uHT) microfluidic droplet platform for activity profiling entire oral...
Liver metastasis is the main cause of colorectal cancer (CRC)‐related death. Neutrophil extracellular traps (NETs) play important roles in CRC progression. Deoxyribonuclease I (DNase I) has been shown to alter NET function by cleaving DNA strands comprising backbone. Moreover, DNase displays high antimetastatic activity multiple tumor models. To circumvent long‐term daily administrations recombinant I, we have developed an adeno‐associated virus (AAV) gene therapy vector specifically express...
We report a novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812. Two major components the mixture, named gausemycins A and B, were isolated, their structures elucidated. The compounds are cyclic peptides with unique peptide core several remarkable structural features, including unusual positions d-amino acids, lack Ca2+ -binding Asp-X-Asp-Gly (DXDG) motif, tyrosine glycosylation arabinose, presence 2-amino-4-hydroxy-4-phenylbutyric acid (Ahpb) chlorinated...
The development of chimeric antigen receptor (CAR) T cell therapy has become a critical milestone in modern oncotherapy. Despite the remarkable vitro effectiveness, problem safety and efficacy CAR against solid tumors is challenged by lack tumor-specific antigens required to avoid on-target off-tumor effects. Spatially separating cytotoxic function cells from tumor recognition provided protein mediators allows for precise control cytotoxicity. Here, high affinity capability bacterial...
We report the molecular mechanism of action gausemycins and isolation new members family, C (1c), D (1d), E (1e), F (1f), minor components mixture. To elucidate gausemycins, we investigated antimicrobial activity most active compounds, A B, in presence Ca2+, other metal ions, phosphate. Gausemycins require a significantly higher Ca2+ concentration for maximum than daptomycin but lower that required malacidine cadasides. Species-specific was found upon testing against wide panel Gram-positive...
Development of CAR-T therapy led to immediate success in the treatment B cell leukemia. Manufacturing therapy-competent functional cells needs robust protocols for ex vivo/in vitro expansion modified T-cells. This step is challenging, especially if non-viral low-efficiency delivery are used generate cells. Modern imperfect since non-specific stimulation results rapid outgrowth CAR-negative T cells, and removal feeder from mixed cultures necessitates additional purification steps. To develop...
Identifying high-affinity antibodies in human serum is challenging due to extremely low number of circulating B cells specific the desired antigens. Delays caused by a lack information on immunogenic proteins viral origin hamper development therapeutic antibodies. We propose an efficient approach allowing for enrichment against pathogen with simultaneous epitope mapping, even absence structural about pathogenic immunogens. To screen from blood recovered donors, only transcriptome required...
Microbial communities are self-controlled by repertoires of lethal agents, the antibiotics. In their turn, these antibiotics regulated bioscavengers that selected in course evolution. Kinase-mediated phosphorylation represents one general strategies for emergence antibiotic resistance. A new subfamily AmiN-like kinases, isolated from Siberian bear microbiome, inactivates amicoumacin phosphorylation. The nanomolar substrate affinity defines AmiN as a phosphotransferase with unique catalytic...
Delivering protein therapeutics specifically into target cells and tissues is a promising avenue in medicine. Advancing this process will significantly enhance the efficiency of designed drugs. In regard, natural membrane-based systems are particular interest. Extracellular vesicles (EVs), being bilayer lipid particles secreted by almost all types cells, have several principal advantages: biocompatibility, carrier stability, blood–brain barrier penetrability, which make them perspective tool...
The biodiversity of microorganisms is maintained by intricate nets interactions between competing species. Impaired functionality human microbiomes correlates with their reduced originating from aseptic environmental conditions and antibiotic use. Microbiomes wild animals are free these selective pressures. Microbiota provides a protecting shield invasion pathogens in the wild, outcompeting growth specific ecological niches. We applied ultrahigh-throughput microfluidic technologies for...
Significance Developed quantum mechanics/molecular mechanics (QM/MM) supercomputation is used to identify maturation of immunoglobulin (Ig) reactivity through optimization amino acids in the catalytic core, focused on enhanced nucleophilic attack phosphorus. A computationally optimized variant, l -Leu47Lys, delivers 340-fold enhancement for paraoxon relative wild-type Ig-paraoxonase resulting from substrate-induced ionization Tyr37 nucleophile. Variant antibody stereoselectivity toward a...
The global spread of antibiotic resistance is forcing the scientific community to find new molecular strategies counteract it. Deep functional profiling microbiomes provides an alternative source for discovery novel producers and probiotics. Recently, we implemented this ultrahigh-throughput screening approach isolation Bacillus pumilus strains efficiently producing ribosome-targeting amicoumacin A (Ami). Proteomics metabolomics revealed essential insight into activation Ami biosynthesis....
Organophosphate toxins (OPs) are the most toxic low-molecular compounds. The extremely potent toxicity of OPs is determined by their specificity toward nerve system. Human butyrylcholinesterase (hBChE) a natural bioscavenger against broad spectrum OPs, which makes it promising candidate for development DNA-encoded bioscavengers. high values protective index observed recombinant hBChE (rhBChE) make appropriate therapy OP poisoning, especially in case highly warfare agents. Nevertheless,...
Gram-negative pathogens represent an urgent threat due to their intrinsic and acquired antibiotic resistance. Many recent drug candidates display prominent antimicrobial activity against Gram-positive bacteria being inefficient pathogens. Ultrahigh-throughput, microfluidics-based screening techniques a new paradigm for deep profiling of antibacterial discovery. A key stage this technology is based on single-cell cocultivation microbiome biodiversity together with reporter fluorescent...
Significance DNA libraries are predisposed to template mispairing during conventional “bulk” PCR, leading the loss of unique sequences. The latter is facilitated by nonuniform distribution templates frequently observed in libraries. These effects result a prominent reduction original diversity. encapsulation repertoires liquid droplets abolishes fundamental advantages emulsion PCR (ePCR) over bulk illustrated deep sequencing and mathematical modeling, which provide general strategy for ePCR...
Butyrylcholinesterase (BChE) is considered as an efficient stoichiometric antidote against organophosphorus (OP) poisons. Recently we utilized combination of calculations and ultrahigh-throughput screening (uHTS) to select BChE variants capable catalytic destruction OP pesticide paraoxon. The purpose this study was elucidate the molecular mechanism underlying enzymatic hydrolysis paraoxon by using hybrid quantum mechanical/molecular mechanical (QM/MM) calculations. Detailed analysis...
The bacterium Streptomyces sp. KMM 9044 from a sample of marine sediment collected in the northwestern part Sea Japan produces highly chlorinated depsiheptapeptides streptocinnamides A (1) and B (2), representatives new structural group antibiotics. structures 1 2 were determined using nuclear magnetic resonance mass spectrometry studies confirmed by series chemical transformations. Streptocinnamide potently inhibits Micrococcus 1467, Arthrobacter ATCC 21022, Mycobacterium smegmatis MC2 155.
Abstract The development of CAR-T specific therapy made a revolution in modern oncology. Despite the pronounced therapeutic effects, this novel approach displayed several crucial limitations caused by complications pharmacokinetics and pharmacodynamics controls. presence severe medical initiated set attempts aimed to regulate their activity vivo. We propose apply barnase-barstar system control cytotoxic antitumor cells. To menage regulation targeting effect we use barstar-modified cells...
Natural compounds continue to serve as the most fruitful source of new antimicrobials. Analysis bacterial genomes have revealed that biosynthetic potential antibiotic producers by far exceeds number already discovered structures. However, due repeated discovery known substances, it has become necessary change both approaches search for antibiotics and sources producer strains. The pressure natural selection diversity interactions in symbiotic communities make animal microbiomes promising...
Staphylococcus aureus is a common human pathogen that particularly often associated with antibiotic resistance. The eradication of this ubiquitous infectious agent from its ecological niches and contaminated surfaces especially complicated by excessive biofilm formation persisting cells, which evade the antibacterial activity conventional antibiotics. Here, we present an alternative view problem specific S. eradication. constitutive heterologous production highly bacteriolytic protease...
The discovery of antibody-mediated catalysis was a breakthrough that showed antibody function is not limited to specific binding interactions, and immunoglobulins (Igs) may also chemically transform their target antigens. Recently, so-called "natural catalytic antibodies" have been intimately linked with several pathologies, where they either protect the organism or contribute development autoimmune abnormalities. Previously, we myelin-reactive autoantibodies from patients multiple sclerosis...
Pemphigus vulgaris is a severe, socially significant autoimmune disease associated with autoantibodies to the desmoglein 3 antigen. The affects all age groups, beginning at 18 years of age; mortality rate pemphigus can reach as high 50%, depending on patient's and number other factors. There no highly selective or personalized therapy for moment. One well-known therapeutic approaches use rituximab, an anti-CD20 antibody that help achieve B cell depletion in peripheral blood. To solve problem...
The global spread of antibiotic resistance marks the end era conventional antibiotics. Mankind desires new molecular tools to fight pathogenic bacteria. In this regard, development antimicrobials based on antimicrobial peptides (AMPs) is again particular interest. AMPs have various mechanisms action bacterial cells. Moreover, been reported be efficient in preclinical studies, demonstrating a low level formation. Thanatin small, beta-hairpin peptide with bacterial-specific mode action,...