- Lectin-Modified Magnetic Nano-PLGA for Photodynamic Therapy In Vivo
The extreme aggressiveness and lethality of many cancer types appeal to the problem of the development of new-generation treatment strategies based on smart materials. The targeted delivery of nanoparticles to specific cancer cell receptors is believed to be such a strategy; however, there are no targeted nano-drugs that have successfully completed clinical trials to date. To meet the challenge, the team of the Laboratory of Molecular Immunology of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, the Laboratory for Biochemical Research of Carcinogenesis of the Moscow Institute of Physics and Technology, and the Department of Nanobiomedicine of the Sirius University, have developed an alternative method of oncotherapy.
- RALF peptides modulate immune response in the moss Physcomitrium patens
Plants utilize small secreted peptides as important mediators of many processes, from growth and development to response to stress conditions. One of such regulators is the conservative 5 kDa cysteine-rich RALF (Rapid Alkalinization Factor) peptide family, which is widely present in terrestrial plants. RAPID ALKALINIZATION FACTOR (RALFs) are peptides that regulate multiple physiological processes in plants. This peptide family has considerably expanded during land plant evolution, but the role of ancient RALFs in modulating stress responses is unknown
- Antibody fragment-drug conjugates selectively eliminate GD2-expressing tumor cells
Employing antibody fragments instead of full-length antibodies in antibody-drug conjugates can facilitate accumulation of the therapeutics in the tumor and reduce their side effects. Scientists from the Laboratory of molecular immunology together with colleagues from the Laboratory of cell interactions, the Laboratory of molecular diagnostics at IBCh RAS, and other Russian Institutes have for the first time developed GD2-specific antibody fragment-drug conjugates. Minibody and scFv fragment conjugates with the tubulin-inhibiting drugs MMAE and MMAF manifested strong cytotoxic and cytostatic effects in GD2-positive neuroblastoma and melanoma cell lines.
- 5-(Perylen-3-ylethynyl)uracil as an antiviral scaffold: Potent suppression of enveloped virus reproduction by 3-methyl derivatives in vitro
A group of scientists from the Laboratory of Molecular Design and Synthesis, the Protein Growth and Differentiation Factor Expression Group of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, the Institute of Poliomyelitis and other institutes synthesized a series of compounds based on 5-(perylene-3-ylethynyl)uracil and studied their antiviral properties and mechanism of action. Previous studies of this class of compounds have suggested controversial types of mechanisms of action. Nonetheless providing comparable high activity. The present study showed that, upon irradiation with light, amphiphilic compounds accumulated in cell and viral membranes inhibit the entry of enveloped viruses into the cell.
- Prophage-derived regions in Curtobacterium genomes: good things, small packages
Curtobacterium is a genus of Gram-positive bacteria within the order Actinomycetales. Some Curtobacterium species are harmful pathogens of agricultural crops such as soybean, dry beans, peas, sugar beet and beetroot, which occur throughout the world. About 200 publicly available genomes of Curtobacterium species, including environmental metagenomic sequences, were inspected for the presence of sequences of possible prophage origin using bioinformatic methods.
- Use of an Integrated Approach Involving AlphaFold Predictions for the Evolutionary Taxonomy of Duplodnaviria Viruses
One of the challenging tasks of Duplodnaviria taxonomy is the classification of high-ranked taxa, including families and orders. In this study, the team of scientists from the Laboratory of molecular bioengineering IBCh RAS in collaboration with the colleagues from the Limnological Institute analized the evolutionary relationships of conserved viral proteins, representing different viruses, including all classified Duplodnaviria families, using AlphaFold modelling.
- Chemogenetic emulation of intraneuronal oxidative stress affects synaptic plasticity
The members of the redox biology group and the Laboratory of molecular technologies from the Department of Metabolism and Redox Biology, IBCH RAS, in the collaboration with colleagues from Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, and Pirogov Russian National Research Medical University, using a well-established model of long-term potentiation, revealed that neuronal oxidative stress affects synaptic plasticity.
- Study of aging of contrast nanoparticles for MRI
December 22, 2022
A group of scientists from the Laboratory of Molecular Immunology of the IBCh RAS, GPI RAS and a several other scientific Institutes investigated biotransformation of magnetic nanoparticles in the body and the effect of this process both on the metabolism of the iron and on reducing the contrast properties of nanoparticles during imaging. For a long time, it remained unclear what happens in the long term with nanoparticle contrasts for MRI after their distribution in tissues. In addition, magnetic particle biodegradation is accompanied by abundant release of iron ions, which can cause toxic effects. A recent study published in the high-ranking Journal of Nanobiotechnology clarified these issues.
- New Type of Interaction of Snake Three-Finger α-Neurotoxins with Nicotinic Acetylcholine Receptors
December 14, 2022
Nicotinic acetylcholine receptor of α7 type (α7-nAChR) presented in the nervous and immune systems and epithelium is a promising therapeutic target for cognitive disfunctions and cancer treatment. Weak toxin from venom of cobra Naja kaouthia (WTX) is a non-conventional three-finger α-neurotoxin from Naja kaouthia venom, targeting α7-nAChR with weak affinity. There were no data on interaction mode of non-conventional neurotoxins with α7-nAChR.
- Identification of HLA-B*27-bound peptides recognized by TCRs associated with ankylosing spondylitis
December 13, 2022
Ankylosing spondylitis is an autoimmune rheumatological disease, where aberrant immune response against self-antigens is considered as a main trigger of the pathology. Up to date identification of antigen epitopes recognized by specific T cell receptors (TCRs), especially self-epitopes, remains tricky challenge and there is the very limited list of TCRs with characterized antigen specificity.
- Relationship between phenolic compounds and antioxidant activity in berries and leaves of raspberry genotypes and their genotyping using SSR markers
November 21, 2022
In recent years, the enrichment of fruits and berries with biologically active substances, in particular, antioxidants has received increased development in breeding (the creation of functional food). Researchers from the Forest Biotechnology Group of the FIBCh, together with colleagues from other institutes, studied the content of total phenols, flavonoids and anthocyanins, their relationship with the antioxidant activity of berries and leaves of various raspberry cultivars of Russian and foreign origin, as well as new breeding lines.
- A Single Fluorescent Protein-Based Indicator with a Time-Resolved Fluorescence Readout for Precise pH Measurements in the Alkaline Range
November 17, 2022
The real-time monitoring of the intracellular pH in live cells with high precision represents an important methodological challenge. Although genetically encoded fluorescent indicators can be considered as a probe of choice for such measurements, they are hindered mostly by the inability to determine an absolute pH value and/or a narrow dynamic range of the signal, making them inefficient for recording the small pH changes that typically occur within cellular organelles.
- Longitudinal profiling of human peripheral blood B cell clonal repertoire: memory B cell persistence and signs of negative and positive selection at the BCR repertoire level
October 12, 2022
Persistence of B cell clones and fine-tuning of their BCRs allow them to respond effectively to repeated immune challenges. Researchers from the Genomics of adaptive immunity department of IBCH in collaboration with colleagues from IITP and Skoltech, performed long-term study of structure and dynamics of BCR repertoire of memory B cells and antibody-secreting cells from peripheral blood of healthy donors.
- A Uniquely Stable Trimeric Model of SARS-CoV-2 Spike Transmembrane Domain
August 31, 2022
Tools created at the Laboratory of Biomolecular Modelling IBCh RAS have been brought together into a computational framework to build a model of SARS-CoV-2 spike transmembrane domain (TMD).
- Impact of Exogenous Application of Potato Virus Y-Specific dsRNA on RNA Interference, Pattern-Triggered Immunity and Poly(ADP-ribose) Metabolism in Potato Plants
August 15, 2022
Methods for inhibition of viral infection induced by spraying plants with preparations of specific double-stranded RNAs (dsRNAs) are currently being actively developed. Researchers from the Laboratory of functional genomics and plant proteomics, the Laboratory of Molecular Diagnostics and the Laboratory of Molecular Bases of Plant Stress Resistance of the Institute of Bioorganic Chemistry RAS studied the contribution of potato plant treatment with dsRNA against potato virus Y (dsRNA-PVY) to two dsRNA-induced plant defense mechanisms: specific RNA interference (RNAi) and non-specific pattern-triggered immunity (PTI).
- SOX9 Protein in Pancreatic Cancer Regulates Multiple Cellular Networks in a Cell-Specific Manner
August 12, 2022
Pancreatic ductal adenocarcinoma is one of the most lethal cancers worldwide. Sex-determining region Y-box protein 9 (SOX9) is upregulated in the majority of pancreatic ductal adenocarcinoma cases. It is hypothesized that the increased expression of pancreatic developmental factor SOX9 is necessary for the formation and maintenance of tumor phenotypes in pancreatic cancer cells.
- Therapeutic efficacy of antibody-drug conjugates targeting GD2-positive tumors
July 19, 2022
Both ganglioside GD2-specific immunotherapy and antibody-drug conjugates (ADCs), as a class of targeted drugs, have demonstrated clinical success as solid tumor therapies in recent years, yet practically no research has been carried out on ADCs directed to ganglioside GD2. In a new study, scientists from the Department of immunology at IBCh RAS in collaboration with colleagues from other Russian institutes for the first time show that clinically relevant anti-GD2 antibody-drug conjugates manifest potent and highly selective cytotoxicity in a wide panel of cell lines with varying GD2 expression and strongly inhibit tumor growth in mouse models of GD2-positive solid cancer.
- Synthesis of New 5ʹ-Norcarbocyclic Aza/Deaza Purine Fleximers - Noncompetitive Inhibitors of E.coli Purine Nucleoside Phosphorylase
July 11, 2022
Scientists from the Laboratory of biosynthesis of physiologically active compounds and Laboratory of biopharmaceutical technologies (IBCH RAS) and Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences synthesized a new series of flexible 5′-norcarbocyclic aza/deaza-purine nucleoside analogs and evaluated as potential inhibitors of E. coli purine nucleoside phosphorylase.
- Positively charged black hole quencher (BHQ) derivatives as external SERS active responsive elements of biosensors
July 8, 2022
Scientists from the Group of molecular tools for living system studies (IBCh RAS), Department of chemistry of Natural Compounds (Faculty of Chemistry, MSU) and Osipyan Institute of Solid State Physics, together with the Laboratory of Molecular Design and Synthesis (IBCh RAS), have developed external SERS-active responsive elements based on positively charged black hole quencher (BHQ) derivatives.
- Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities
July 5, 2022
Plant lignans are active components of many herbs, which makes them the research objects for therapeutic agents development for practical use. They provide diverse naturally-occurring pharmacophores, which allows them to interact with various enzymes, receptors, ion channels and signaling molecules.
- Streptocinnamides A and B, Depsipeptides from Streptomyces sp. KMM 9044
July 1, 2022
A new structural group of antibiotics produced by a new strain Streptomyces sp. KMM 9044 was discovered as a result of teamwork of scientists from the Institute of Bioorganic Chemistry (IBCh RAS) and the Elyakov Pacific Institute of Bioorganic Chemistry (TIBOCh RAS).
- Capsule-Targeting Depolymerases Derived from Acinetobacter baumannii Prophage Regions
June 16, 2022
A team of scientists from the Laboratory of molecular bioengineering IBCh RAS together with the colleagues from other Russian Institutes bioinformatically predicted and recombinantly produced several different depolymerases encoded in the prophage regions of Acinetobacter baumannii genomes. For two depolymerases, the specificity to capsular polysaccharides (CPSs) of A. baumannii belonging to K1 and K92 capsular types (K types) was determined. These enzymes can be considered as suitable candidates for the development of new antibacterials against corresponding A. baumannii K types.
- Evolution of Phage Tail Sheath Protein
June 16, 2022
A team of scientists from the Laboratory of molecular bioengineering IBCh RAS analysed 112 contractile phage tail sheath proteins (TShP) representing different groups of bacteriophages and archaeal viruses with myoviral morphology have been modelled with the novel machine learning software, AlphaFold 2. The common core domain of all studied sheath proteins, including viral and T6SS proteins, comprised both N-terminal and C-terminal parts, whereas the other parts consisted of one or several moderately conserved domains, presumably added during phage evolution.
- Heterogeneity of the GFP fitness landscape and data-driven protein design
June 16, 2022
Understanding the relationship between genotype and phenotype, the fitness landscape, elucidates the fundamental laws of heredity (Canale et al. 2018) and may ultimately create novel methods of protein design (Alley et al. 2019). The fitness landscape is often conceptualised as a multidimensional surface (Kondrashov and Kondrashov, 2015) with one dimension representing fitness, or another phenotype, and the other dimensions each representing a genotype’s locus.
- Synthesis of 2-chloropurine ribosides with chiral amino acid amides at C6 and their evaluation as A1 adenosine receptor agonists
June 14, 2022
The team of scientists from the Department of biotechnology and the Laboratory of structural biology of ion channels IBCh RAS synthesized a series of adenosine analogs as purine ribonucleosides bearing amino acid amides at the C6 position of 2-chloropurine.
- Сytoskeleton protein Zyxin inhibits retinoic acid signaling by destabilizing maternal mRNA of nuclear receptor RXRγ
May 20, 2022
In a new study, researchers from the Laboratory of molecular bases of embryogenesis, Institute of Bioorganic Chemistry, Russian Academy of Sciences, demonstrated the versatility of the previously discovered mechanism of maternal genes mRNA destabilization caused by an interaction between the cytoskeletal protein Zyxin and the mRNA-binding factor Ybx1, showing that the same mechanism governs the retinoic acid signaling pathway during early embryonic development.
- Genetically-encoded BRET-activated photodynamic therapy for the treatment of deep-seated tumors
March 16, 2022
Being targeted to tumor cells, genetically-encoded NanoLuc-miniSOG construct generates internal light source and sensitizer pair, which makes possible PDT effect under BRET activation to treat tumors at virtually unlimited depth.
- Estimation of copy number variability from the high-throughput sequencing data
March 14, 2022
Traditionally, cytogenetic and molecular cytogenetic methods are used to detect chromosomal abnormalities. With the development of sequencing technologies, new approaches have become available to identify structural variations ranging from 50 bp. Researchers from the Laboratory of Molecular Oncology of Institute of Bioorganic Chemistry of the Russian Academy of Sciences and the Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency developed an approach for construction of CNV validation set at the exon level and evaluated the efficiency of CNV calling tools designed for whole exome sequencing data.
- 7,8-Dihydro-8-oxo-1,N6-ethenoadenine: an exclusively Hoogsteen-paired thymine mimic in DNA that induces A→T transversions in Escherichia coli
March 3, 2022
Scientists from the Group of molecular tools for living system studies and Laboratory of molecular diagnostics (IBCH) together with the colleagues from Skoltech, the Federal Research Center for Physical and Chemical Medicine, Massachusetts Institute of Technology (USA) and Instituto de Química-Física Rocasolano (Spain) has developed a DNA modification, 7,8-dihydro-8-oxo-1,N6-ethenoadenine (oxo-ϵA), a non-natural synthetic base that combines structural features of two naturally occurring DNA lesions (7,8-dihydro-8-oxoadenine and 1,N6-ethenoadenine).