A5007402023- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Insect and Pesticide Research
- Cholinesterase and Neurodegenerative Diseases
- Venomous Animal Envenomation and Studies
- Gene Regulatory Network Analysis
- Plant and Biological Electrophysiology Studies
- Neuroscience and Neuropharmacology Research
- Chemical Synthesis and Analysis
- Alkaloids: synthesis and pharmacology
- Biochemical and Structural Characterization
- Pharmacological Receptor Mechanisms and Effects
- Biochemical effects in animals
- Synthesis and Biological Evaluation
- Morphological variations and asymmetry
- Bioinformatics and Genomic Networks
- Free Radicals and Antioxidants
- Molecular Junctions and Nanostructures
- Chemical synthesis and pharmacological studies
- Computational Drug Discovery Methods
- Cell Image Analysis Techniques
- Neurobiology and Insect Physiology Research
Institute of Bioorganic Chemistry
2015-2021
Agricultural University of Georgia
2019
Sechenov University
2019
Pasteur Hellenic Institute
2019
National Research Nuclear University MEPhI
2019
Institute of Evolutionary Physiology and Biochemistry
2013
Stony Brook University
2012
Cholinergic dysfunction in Alzheimer’s disease (AD) can be mediated by the neuronal α7 nicotinic acetylcholine receptor (α7nAChR). Beta-amyloid peptide (Aβ) binds to α7nAChR, disrupting receptor’s function and causing neurotoxicity. In vivo not only Aβ but also its modified forms drive AD pathogenesis. One of these forms, iso-Aβ (containing an isomerized Asp7 residue), shows increased neurotoxicity vitro stimulates amyloidogenesis vivo. We suggested that such effects are α7nAChR-dependent....
6-Bromohypaphorine (6-BHP) has been isolated from the marine sponges Pachymatisma johnstoni, Aplysina sp., and tunicate Aplidium conicum, but data on its biological activity were not available. For nudibranch mollusk Hermissenda crassicornis no endogenous compounds known, here we describe isolation of 6-BHP this effects different nicotinic acetylcholine receptors (nAChR). Two-electrode voltage-clamp experiments chimeric α7 nAChR (built chicken ligand-binding glycine receptor transmembrane...
Abstract Despite some success for small molecules, elucidating structure–function relationships biologically active peptides — the ligands various targets in organism remains a great challenge and calls development of novel approaches. Some us recently proposed Protein Surface Topography (PST) approach, which benefits from simplified representation biomolecules’ surface as projection maps, enables exposure dependencies. Here, we use PST to uncover “activity pattern” α-conotoxins neuroactive...
The proteins of the Ly6 family have a three-finger folding as snake venom α-neurotoxins, targeting nicotinic acetylcholine receptors (nAChRs), and some them, like mammalian secreted Ly6/uPAR protein (SLURP1) membrane-attached Ly-6/neurotoxin (Lynx1), also interact with distinct nAChR subtypes. We believed that synthetic fragments these endogenous might open new ways for drug design because nAChRs are well-known targets developing analgesics drugs against neurodegenerative diseases. Since...
Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which be explained by phospholipid hydrolysis, each enzyme has a specific effect. We earlier demonstrated capability several venom with different enzymatic, cytotoxic, anticoagulant antiproliferative properties, to...
Many peptide ligands of nicotinic acetylcholine receptors (nAChRs) contain a large number positively charged amino acid residues, striking example being conotoxins RgIA and GeXIVA from marine mollusk venom, with an arginine content >30%. To determine whether peptides built exclusively residues will interact different nAChR subtypes or their structural homologs such as the acetylcholine-binding protein ligand-binding domain <i>α</i>9 subunit, we synthesized series R3, R6, R8, R16...
Human SLURP-1 is a secreted protein of the Ly6/uPAR/three-finger neurotoxin family that co-localizes with nicotinic acetylcholine receptors (nAChRs) and modulates their functions. Conflicting biological activities at various nAChR subtypes have been based on heterologously produced containing N- and/or C-terminal extensions. Here, we report chemical synthesis 81 amino acid residue human protein, characterization its 3D structure by NMR, activity subtypes. Radioligand assays indicated...
α-Conotoxins from Conus snails are capable of distinguishing muscle and neuronal nicotinic acetylcholine receptors (nAChRs). α-Conotoxin RgIA αO-conotoxin GeXIVA, blocking α9α10 nAChR, potential analgesics. Typically, α-conotoxins bind to the orthosteric sites for agonists/competitive antagonists, but GeXIVA was proposed attach allosterically, judging by electrophysiological experiments on nAChR. We decided verify this conclusion radioligand analysis in competition with α-bungarotoxin (αBgt)...
Several novel bisbenzylisoquinoline alkaloids (BBIQAs) have recently been isolated from a Matis tribe arrow poison and shown by two-electrode voltage-clamp to inhibit mouse muscle nicotinic acetylcholine receptors (nAChR). Here, using radioligand assay with Aplysia californica AChBP radioiodinated α-bungarotoxin ([125I]-αBgt), we show that BBIQA1, BBIQA2, d-tubocurarine (d-TC) similar affinities nAChR orthosteric site. However, competition [125I]-αBgt for binding the Torpedo muscle-type...
In recent years the analysis of noise in gene expression has widely attracted attention experimentalists and theoreticians. Experimentally, approaches based on vivo fluorescent reporters single cells appear to be straightforward effective tools for bacteria yeast. However, transferring these multicellular organisms presents many methodological problems. Here we describe our approach measure between-nucleus variability (noise) primary morphogenetic gradient Bicoid (Bcd) precellular blastoderm...
Elucidation of the structural basis pharmacological differences for highly homologous α7 and α9 nicotinic acetylcholine receptors (nAChRs) may shed light on their involvement in different physiological functions diseases. Combination site-directed mutagenesis electrophysiology is a powerful tool to pinpoint key amino-acid residues receptor ligand-binding site, but nAChRs it complicated by poor expression fast desensitization. Here, we probed properties α7/α9 nAChR mutants proposed simple...
Diverse ligands of the muscle nicotinic acetylcholine receptor (nAChR) are used as relaxants during surgery. Although a plethora such molecules exists in market, there is still need for new drugs with rapid on/off-set, increased selectivity, and so forth. We found that pyrroloiminoquinone alkaloid Makaluvamine G (MG) inhibits several subtypes receptors ionotropic γ-aminobutiric acid receptors, showing higher affinity moderate selectivity toward nAChR. The action MG on latter was studied by...
A three-dimensional database search has been applied to design a series of endo- and exo-3-(pyridin-3-yl)bicyclo[2.2.1]heptan-2-amines as nicotinic receptor ligands. The synthesized compounds were tested in radioligand binding assay on rat cortex against [3H]-cytisine [3H]-methyllycaconitine measure their affinity for α4β2* α7* receptors. new derivatives showed some preference the over subtype, with being dependent endo/exo isomerism methylation degree basic nitrogen. endo primary amines...
Slow-channel congenital myasthenic syndromes (SCCMSs) are rare genetic diseases caused by mutations in muscle nicotinic acetylcholine receptor (nAChR) subunits. Most of the known SCCMS-associated localize at transmembrane region near ion pore. Only two SCCMS point extracellular domains binding site, α1(G153S) being one them. In this work, a combination molecular dynamics, targeted mutagenesis, fluorescent Ca2+ imaging and patch-clamp electrophysiology has been applied to G153S mutant nAChR...