Galina Sergeev

Institute of Bioorganic Chemistry

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Dieter Kaufmann

Clausthal University of Technology

Viktor A. Zapol’skii

Clausthal University of Technology

Jan C. Namyslo

Clausthal University of Technology

Mimoza Gjikaj

Clausthal University of Technology

Mark Brönstrup

Helmholtz Centre for Infection Research

Dirk Menche

University of Bonn

K. V. Homel

National Academy of Sciences of Belarus

Thomas Böldicke

Helmholtz Centre for Infection Research

Irina Haidukevich

National Academy of Sciences of Belarus

Stefan Somplatzki

Helmholtz Centre for Infection Research

Cooperative Institutions

Helmholtz Centre for Infection Research

National Academy of Sciences of Belarus

Clausthal University of Technology

Technische Universität Braunschweig

Institute of Bioorganic Chemistry

University of Bonn

Heidelberg University

ORCID

Republican Research and Practical Center for Epidemiology and Microbiology

German Center for Infection Research

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Identifizierung von Substanzen zur Verminderung der Pathogenität von Vibrio cholerae durch neuentwickelte Hochdurchsatz-Screeningverfahren

Galina Sergeev

Vibrio cholerae ist ein Gram-negativer humanpathogener Erreger, der die Durchfallerkrankung Cholera verursacht. Bei Cholera handelt es sich um eine akute intestinale Infektion, die zu starken plotzlich auftretenden Durchfallen, und somit innerhalb kurzester Zeit zu einem hohen Wasser- und Elektrolytverlust fuhrt. Die Ubertragung von V. cholerae erfolgt hauptsachlich uber die Zufuhr von kontaminiertem Wasser, seltener uber die Aufnahme von kontaminierter Nahrung wie Fisch und Meeresfruchte. Besonders Entwicklungslander ohne adaquate Trinkwasseraufarbeitung oder Trennung von Abwassern und Frischwasser leiden unter Cholera-Epidemien. Aufgrund der steigenden Resistenzentwicklung gegen die bisher eingesetzten Antibiotika zur Behandlung von V. cholerae Infektionen, besteht ein dringender Bedarf an der Entwicklung neuer spezifischer Therapeutika. Fur die Suche nach neuen Wirkstoffen wurden im Rahmen dieser Arbeit vier unterschiedliche Mikrotiterplatten-basierte Hochdurchsatz-Screening¬verfahren entwickelt und etabliert. Es handelt sich dabei um Verfahren zur Bestimmung von 1. der Wachstumsrate, 2. der Choleratoxin-Expression, 3. der Protoporphyrinogen IX Oxidase-Aktivitat und 4. der bakteriellen Adhasion an Epithel¬zellen. Die Verfahren 1-3 wurden fur ein Screening nach aktiven Substanzen genutzt. Im Rahmen eines umfangreichen Screening wurden drei neuen Substanzen mit antibakteriellen Eigenschaften spezifisch gegen V. cholerae identifiziert. Anschliesend erfolgten erste experimentelle Untersuchungen zur Targetidentifizierung der aktivsten Substanz vz0825, mit Hilfe einer Gesamtgenom-Sequenzierung des Genom-Pools aus 15 gegen diese Substanz resistenten Mutanten. Im Choleratoxin-Screening wurden sechs neue Substanzen identifiziert, die die Expression der Pathogenitatsfaktoren Choleratoxin und Toxin coregulated Pili inhibieren. Durch Anwendungen von Real Time-PCR-Analysen und Microarray-Analysen erfolgten die ersten experimentellen Untersuchungen zur Targetidentifizierung.

10.24355/dbbs.084-201205301204-0

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Design, Synthesis, and Biological Evaluation of Simplified Side Chain Hybrids of the Potent Actin Binding Polyketides Rhizopodin and Bistramide

ChemMedChem (2015)

Daniel Herkommer Sandra Dreisigacker Galina Sergeev Florenz Sasse Holger Gohlke

The natural products rhizopodin and bistramide belong to an elite class of highly potent actin binding agents. They show powerful antiproliferative activities against a range of tumor cell lines, with IC50 values in the low-nanomolar range. At the molecular level they disrupt the actin cytoskeleton by binding specifically to a few critical sites of G-actin, resulting in actin filament stabilization. The important biological properties of rhizopodin and bistramide, coupled with their unique and intriguing molecular architectures, render them attractive compounds for further development. However, this is severely hampered by the structural complexity of these metabolites. We initiated an interdisciplinary approach at the interface between molecular modeling, organic synthesis, and chemical biology to support further biological applications. We also wanted to expand structure-activity relationship studies with the goal of accessing simplified analogues with potent biological properties. We report computational analyses of actin-inhibitor interactions involving molecular docking, validated on known actin binding ligands, that show a close match between the crystal and modeled structures. Based on these results, the ligand shape was simplified, and more readily accessible rhizopodin-bistramide mimetics were designed. A flexible and modular strategy was applied for the synthesis of these compounds, enabling diverse access to dramatically simplified rhizopodin-bistramide hybrids. This novel analogue class was analyzed for its antiproliferative and actin binding properties.

Docking (animal)

Molecular binding

Molecular model

Chemical Biology

10.1002/cmdc.201402508

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CCDC 1034618: Experimental Crystal Structure Determination

The Cambridge Structural Database (2015)

Viktor A. Zapol’skii Jan C. Namyslo Galina Sergeev Mark Brönstrup Mimoza Gjikaj

10.5517/cc13qls6

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Functional inhibition of transitory proteins by intrabody-mediated retention in the endoplasmatic reticulum

Methods (2011)

Thomas Böldicke Stefan Somplatzki Galina Sergeev Peter P. Mueller

10.1016/j.ymeth.2011.10.008

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Молекулярно-генетическая диагностика расстройств аутистического спектра

Вестник Совета молодых учёных и специалистов Челябинской области (2016)

Т. В. Докукина С. А. Марчук И. В. Гайдукевич Galina Sergeev

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Genetic characteristics of the bred group of deer and assessment of gene flow from it to natural populations

Proceedings of the National Academy of Sciences of Belarus Biological Series (2025)

A. A. Valnisty K. V. Homel Galina Sergeev М. Е. Никифоров

Here we present the results of genetic analysis of an artificial deer population, inhabiting an enclosed territory near Lida. The analysis was aimed at determining the precise origins and genetic characteristics of the population and disco vering presence of any gene flow between the artificial population and the wild deer of the region. We employed mitochondrial control region haplotypes analysis to identify origins and possible matrilineal hybrids, and hybrid classification of migration analysis based on microsatellite data to discover hybrid specimens and gene flow, respectively. We have determined that the artificial population in question belongs to the species Cervus canadensis sibiricus , or Altai wapiti, originates in the South Altai region, and possesses mediocre genetic diversity as can be expected from a population of this size. While singular results of hybrid analysis seem to indicate a possibility of rare interbreeding between escaped wapiti and wild deer, there are no indicators of any substantial gene flow from the artificial population into the wild, but we believe that it still warrants additional attention in order to prevent undesirable introgression.

10.29235/1029-8940-2025-70-1-40-47

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High-throughput screening and whole genome sequencing identifies an antimicrobially active inhibitor of Vibrio cholerae

BMC Microbiology (2014)

Galina Sergeev Sambit Roy Michael Jarek Viktor A. Zapol’skii Dieter Kaufmann

Pathogenic serotypes of Vibrio cholerae cause the life-threatening diarrheal disease cholera. The increasing development of bacterial resistances against the known antibiotics necessitates the search for new antimicrobial compounds and targets for this pathogen.A high-throughput screening assay with a Vibrio cholerae reporter strain constitutively expressing green fluorescent protein (GFP) was developed and applied in the investigation of the growth inhibitory effect of approximately 28,300 structurally diverse natural compounds and synthetic small molecules. Several compounds with activities in the low micromolar concentration range were identified. The most active structure, designated vz0825, displayed a minimal inhibitory concentration (MIC) of 1.6 μM and a minimal bactericidal concentration (MBC) of 3.2 μM against several strains of V. cholerae and was specific for this pathogen. Mutants with reduced sensitivity against vz0825 were generated and whole genome sequencing of 15 pooled mutants was carried out. Comparison with the genome of the wild type strain identified the gene VC_A0531 (GenBank: AE003853.1) as the major site of single nucleotide polymorphisms in the resistant mutants. VC_A0531 is located on the small chromosome of V. cholerae and encodes the osmosensitive K+-channel sensor histidine kinase (KdpD). Nucleotide exchange of the major mutation site in the wild type strain confirmed the sensitive phenotype.The reporter strain MO10 pG13 was successfully used for the identification of new antibacterial compounds against V. cholerae. Generation of resistant mutants and whole genome sequencing was carried out to identify the histidine kinase KdpD as a novel antimicrobial target.

Cholera

10.1186/1471-2180-14-49

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Development of a multiplex system for determining 11 genetic markers of predisposition to obesity

Proceedings of the National Academy of Sciences of Belarus Chemical Series (2021)

Galina Sergeev Irina Haidukevich A. M. Gorkavaya Maxim Ameliyanovich И. Б. Моссэ

A system has been developed to identify 11 genetic markers associated with the risk of obesity: rs10852521, rs11075990, rs1121980, rs1421085, rs1477196, rs17817449, rs3751812, rs7206790, rs8047395, rs9940128 (FTO gene) and rs1137101 (LEPR gene) by minisequencing (SNaPshot analysis). The conditions for carrying out the amplification and minisequencing reactions, as well as the compositions of the reaction mixtures, were optimized so that the analysis was carried out for all 11 markers simultaneously. The resulting system was tested and showed a high degree of reproducibility and sensitivity required for the detection of these polymorphisms.

Multiplex

Snapshot (computer storage)

Genetic predisposition

10.29235/1561-8331-2021-57-3-300-309

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Reinvestigation of the Nitration of Trichloroethene – Subsequent Reactions of the Products and Evaluation of Their Antimicrobial and Antifungal Activity

European Journal of Organic Chemistry (2015)

Viktor A. Zapol’skii Jan C. Namyslo Galina Sergeev Mark Brönstrup Mimoza Gjikaj

Abstract The nitration reaction of trichloroethene ( 1 ) to main products trichloronitroethene (TCNiE 2 , up to 60.8 %, by GC), 1,1,2,2‐tetrachloro‐1‐nitroethane ( 8 , up to 25.1 %, by GC), and 1,2,2‐trichloro‐2‐nitroethyl [chloro(nitro)methylene]azinate ( 9 , up to 8.0 %, by GC) was comprehensively investigated and optimized. Different 1,1‐diamino‐2‐chloro‐2‐nitroethenes, 2‐nitroethoxyguanidines, and rare O ‐(1,2,2‐trichloro‐2‐nitroethyl) oximes and carbimidoyl halides with unique formulas R–O–N=C(NO 2 )NRR 1 and R–O–N=C(Hal)NRR 1 , respectively, were obtained from these nitration products in yields up to 91 %. The structure of ( E )‐morpholino(nitro)methanone O ‐(1,2,2‐trichloro‐2‐nitroethyl) oxime ( 19 ) was proven by single‐crystal X‐ray diffraction analysis. In addition, the antimicrobial and antifungal activity of the synthesized compounds was examined. Notably, N ‐(1,2,2‐trichloro‐2‐nitroethoxy)‐3,4‐dihydroisoquinoline‐2(1 H )carbimidoyl chloride ( 27 ) inhibited the growth of methicillin‐resistant and sensitive Staphylococcus aureus with minimum inhibitory concentrations of 1.3 μg mL –1 , and reduced the viability of the MCF‐7 cancer cell line with an IC 50 of 0.2 μg/mL.

Nitroethane

Methylene

10.1002/ejoc.201501066

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ChemInform Abstract: Chemistry of Halonitroethenes. Part 3. Reinvestigation of the Nitration of Trichloroethene - Subsequent Reactions of the Products and Evaluation of Their Antimicrobial and Antifungal Activity.

ChemInform (2016)

Viktor A. Zapol’skii Jan C. Namyslo Galina Sergeev Mark Bröenstrup Mimoza Gjikaj

The nitration reaction of trichloroethene to its three main products is comprehensively investigated and optimized.

10.1002/chin.201616067

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