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Multivalent glycopolymers as ligands of lectin-denoted biological targets

Project goals

Multivalent biocompatible polymeric conjugates with various defined carbohydrate epitopes will be synthesized. Carbohydrate structures will be prepared by chemoenzymatic methods using a range of mutant and native glycosidases and glycosyltransferases. The glycoconjugates will be tested as ligands for selected lectins, in particular galectin-3, in biological studies in vitro, namely binding assays and assays in cell cultures. The affinity of glycopolymeric conjugates to lectin targets will be assessed in relation to the glycopolymer structural parameters: the surface density of carbohydrate ligands, their composition and the linker type. Biological studies, structure-activity relationship and the evaluation of prepared conjugates will be realized in cooperation with COST partners and using own infrastructure.

Keywords

carbohydrateenzymatic synthesisgalectinglycopolymerHPMAtarget delivery

Public support

  • Provider

    Ministry of Education, Youth and Sports

  • Programme

    INTER-EXCELLENCE

  • Call for proposals

    INTER-EXCELLENCE 2 (SMSM2016LTC01)

  • Main participants

    Mikrobiologický ústav AV ČR, v. v. i.

  • Contest type

    VS - Public tender

  • Contract ID

    MSMT-15304/2017-1

Alternative language

  • Project name in Czech

    Multivalentní glykopolymery jako ligandy biologických struktur s lektinovou prezentací

  • Annotation in Czech

    Vypracujeme přípravu nových multivalentních biokompatibilních konjugátů HPMA polymerů s různými definovanými oligosacharidovými ligandy. Sacharidové struktury budou připraveny chemoenzymovou syntézou za použití škály mutantních a nativních glykosidas a glykosyltransferas. Výsledné konjugáty budou otestovány jako ligandy pro vybrané lektiny, zvláště pro galektin-3, v biologických studiích in vitro ve vazebných testech a tkáňových kulturách. Bude vyhodnocena studie vztahu mezi strukturou konjugátů a jejich vazebnou afinitou vzhledem k povrchové hustotě sacharidových ligandů, jejich délce, způsobu připojení na polymer a typu kopolymerace polymerního nosiče. Biologické studie, strukturně vazebná analýza a posouzení využitelnosti připravených konjugátů budou realizovány ve spolupráci s partnery projektu COST a s využitím vlastní infrastruktury.

Scientific branches

  • R&D category

    ZV - Basic research

  • CEP classification - main branch

    CE - Biochemistry

  • CEP - secondary branch

    CC - Organic chemistry

  • CEP - another secondary branch

    EI - Biotechnology and bionics

  • 10401 - Organic chemistry
    10608 - Biochemistry and molecular biology
    10609 - Biochemical research methods
    20801 - Environmental biotechnology
    20802 - Bioremediation, diagnostic biotechnologies (DNA chips and biosensing devices) in environmental management
    20803 - Environmental biotechnology related ethics
    20901 - Industrial biotechnology
    20902 - Bioprocessing technologies (industrial processes relying on biological agents to drive the process) biocatalysis, fermentation
    20903 - Bioproducts (products that are manufactured using biological material as feedstock) biomaterials, bioplastics, biofuels, bioderived bulk and fine chemicals, bio-derived novel materials
    30401 - Health-related biotechnology
    30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)
    30403 - Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions [pharmacogenomics, gene-based therapeutics])
    30404 - Biomaterials (as related to medical implants, devices, sensors)
    30405 - Medical biotechnology related ethics
    40401 - Agricultural biotechnology and food biotechnology
    40402 - GM technology (crops and livestock), livestock cloning, marker assisted selection, diagnostics (DNA chips and biosensing devices for the early/accurate detection of diseases) biomass feedstock production technologies, biopharming
    40403 - Agricultural biotechnology related ethics

Completed project evaluation

  • Provider evaluation

    V - Vynikající výsledky projektu (s mezinárodním významem atd.)

  • Project results evaluation

    Specific carbohydrate ligands were prepared by chemoentzymatic synthesis. Novel selective glycopolymers were prepared that had a high affinity for Gal-1 or Gal-3. Selected glycopolymers were tested in new biological studies. In sum, seven publications were published, all with international co-authorship; one publication is in print.

Solution timeline

  • Realization period - beginning

    Jun 1, 2017

  • Realization period - end

    Apr 15, 2020

  • Project status

    U - Finished project

  • Latest support payment

    Feb 24, 2020

Data delivery to CEP

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

  • Data delivery code

    CEP21-MSM-LT-U/01:1

  • Data delivery date

    Jun 15, 2021

Finance

  • Total approved costs

    2,791 thou. CZK

  • Public financial support

    2,791 thou. CZK

  • Other public sources

    0 thou. CZK

  • Non public and foreign sources

    0 thou. CZK

Basic information

Recognised costs

2 791 CZK thou.

Public support

2 791 CZK thou.

100%


Provider

Ministry of Education, Youth and Sports

CEP

CE - Biochemistry

Solution period

01. 06. 2017 - 15. 04. 2020