| Attributes | Values |
|---|
| rdf:type
| |
| rdfs:seeAlso
| |
| Description
| - The essence of this project is rational design of novel compounds of high inhibitory potency to human enzymes involved in RNA/DNA metabolic pathways, especially 5’-nucleotidases. Instrumental for achieving this project goal will be:Molecular cloning, expression and purification of human 5’-nucleotidases. Setting up high-sensitive in vitro activity assays. Rational design of new derivatives of isopolar nucleoside phosphonic acids (nucleotides analogs). This design will be based on analyses of 3D structures of 5’‑nucleotidase complexes deposited in PDB and our in silico modeled complexes. Synthesis of series of novel compounds. In vitro testing/high-throughput screening for inhibitory potency. Detailed kinetic characterization of inhibitory potency and selectivity of newly selected active compounds. In vivo testing/screening of effects of active compounds in a panel of tissue cultures. X-ray structure solving of a complexes of 5’-nucleotidases with inhibitors that display promising potency and selectivity. Rational design of new and optimized compounds based on solved 3D structures.Compounds of strong and selective inhibitory potency are of high medicinal interest as antimetabolites for anticancer and antiviral therapy. (en)
- Základem řešení tohoto projektu je cílené navrhovaní látek s inhibičními účinky na lidské enzymy zapojené v metabolických drahách synthesy a odbourávání RNK/DNK, konkrétně 5'-nukleotidasy. Nástroji k dosažení cílů tohoto projektu bude:Molekulární klonování, exprese a purikace lidských rekombinantních 5´-nukleotidáz. Vypracování vysoce citlivých in vitro testů enzymové aktivity. Cílené navrhování nových derivátů nukleosid fosfonové kyseliny (analogů nukleotidů). Tyto návrhy budou založeny na analýze prostorových struktur komplexů 5´-nukloetidás uložených ve strukturní databázi PDB a počítačem modelovaných komplexů. Syntéza sérií nových látek. In vitro vysoce propustné testování jejich inhibičních účinků na lidské 5´-nukleotiodásy. Přesné kinetické studie selektivity a inhibičního efektu vybraných inhibitorů. In vivo testování účinků inhibitorů na panelu tkáňových kultur. Řešení rentgenové struktury komplexů 5´-nukleotidás a inhibitorů vykazujících vysokou inhibiční účinnost a selektivitu. Cílené navrhování látek s optimalizovanými inhibičními účinky na základě strukturní analýzy výše uvedených komplexů.Sloučeniny vykazující silné a selektivní inhibiční účinky jsou z medicinálního hlediska velice zajímavé jako antimetabolity použitelné při léčení nádorových a virových onemocnění.
|
| Title
| - Structure based drug design of specific nucleotidases inhibitors, potentially pharmacologically important compounds. (en)
- Strukturně inspirovaná synthesa selektivních inhibitorů nukleotidás, poteciálně významných léčiv.
|
| skos:notation
| |
| http://linked.open...avai/cep/aktivita
| |
| http://linked.open...kovaStatniPodpora
| |
| http://linked.open...ep/celkoveNaklady
| |
| http://linked.open...datumDodatniDoRIV
| |
| http://linked.open...i/cep/druhSouteze
| |
| http://linked.open...ep/duvernostUdaju
| |
| http://linked.open.../cep/fazeProjektu
| |
| http://linked.open...ai/cep/hlavniObor
| |
| http://linked.open...hodnoceniProjektu
| |
| http://linked.open...vai/cep/kategorie
| |
| http://linked.open.../cep/klicovaSlova
| - Nucleotidases Nucleotidases inhibitors anticancer activity (en)
|
| http://linked.open...ep/partnetrHlavni
| |
| http://linked.open...inujicichPrijemcu
| |
| http://linked.open...cep/pocetPrijemcu
| |
| http://linked.open...ocetSpoluPrijemcu
| |
| http://linked.open.../pocetVysledkuRIV
| |
| http://linked.open...enychVysledkuVRIV
| |
| http://linked.open...lneniVMinulemRoce
| |
| http://linked.open.../prideleniPodpory
| |
| http://linked.open...iciPoslednihoRoku
| |
| http://linked.open...atUdajeProjZameru
| |
| http://linked.open.../vavai/cep/soutez
| |
| http://linked.open...usZobrazovaneFaze
| |
| http://linked.open...ai/cep/typPojektu
| |
| http://linked.open...ep/ukonceniReseni
| |
| http://linked.open.../cep/vedlejsiObor
| |
| http://linked.open...ep/zahajeniReseni
| |
| http://linked.open...jektu+dodavatelem
| - The main aim of the project was to study cytosolic and mitochondrial nucleotidases, synthesis of their inhibitors and testing their inhibitory activities. Results were published in 19 research papers, only one demonstrates a mutual collaboration between both institutions. Planned goals of the project were accomplished. (en)
- Cílem projektu bylo studium cytosolické a mitochondriální nukleotidasy, příprava jejich inhibitorů a testování jejich inhibičních účinků. Výstupem projektu je 19 publikací, pouze jediná je společná pro obě pracoviště. Plánované cíle projektu byly splněny. (cs)
|
| http://linked.open...tniCyklusProjektu
| |
| is http://linked.open...vavai/riv/projekt
of | - Crystallization of the Effector-Binding Domain of Repressor DeoR from Bacillus subtilis
- A convenient, high-yield synthesis of 1-substituted uracil and thymine derivatives
- Methyl 4-toluenesulfonyloxymethylphosphonate, a new and versatile reagent for the convenient synthesis of phosphonate-containing compounds
- Structural diversity of nucleoside phosphonic acids as a key factor in the discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase
- Oligomerization of adenosin-5´-O-ylmethylphosphonate, an isopolar AMP analogue: Evaluation of the route to short oligoadenylates
- Straightforward synthesis of 3´-deoxy-3´,4´-didehydronucleoside-5´-aldehydes via 2´,3´-O-orthoester group elimination: a simple route 3´,4´-didehydronucleosides
- Identification of 3,4-Dihydroisoquinoline-2(1H)-sulfonamides as Potent Carbonic AnhydraseInhibitors: Synthesis, Biological Evaluation, and Enzyme-Ligand X-ray Studies
- Identification of Carbonic Anhydrase I Immunodominant Epitopes Recognized by Specific Autoantibodies Which Indicate an Improved Prognosis in Patients with Malignancy after Autologous Stem Cell Transplantation
- Structural basis for the interaction between carbonic anhydrase and 1,2,3,4-tetrahydroisoquinolin-2-ylsulfonamides
- Structure of the mouse galectin-4 N-terminal carbohydrate-recognition domain reveals the mechanism of oligosaccharide recognition
- Inhibition of human thymidine phosphorylase by conformationally constrained pyrimidine nucleoside phosphonic acids and their %22open-structure%22 isosteres
- 5 '-O-Methylphosphonate nucleic acids-new modified DNAs that increase the Escherichia coli RNase H cleavage rate of hybrid duplexes
- Kinetic and structural characterization of an alternatively spliced variant of human mitochondrial 5'(3')-deoxyribonucleotidase
- Tetrofuranose nucleoside phosphonic acids: Synthesis and properties
- Synthesis of novel deoxynucleoside S-methylphosphonic acids using S-(diisopropylphosphonomethyl)isothiouronium tosylate, a new equivalent of mercaptomethylphosphonate
- 5´-Epimeric 3´-deoxy-3´,4´-didehydronucleoside-5´-C-phosphonates: synthesis and structural assignment by NMR and X-ray analyses
- The crystal structure of protease Sapp1p from Candida parapsilosis in complex with the HIV protease inhibitor ritonavir
- Towards crystal structures of antibodies and transcription factors
- Structures of human cytosolic and mitochondrial nucleotidases: implications for structure-based design of selective inhibitors
- A Ferrier-Type Allylic Rearrangement of 3´-Deoxy-3´,4´-didehydronucleosides Mediated by DMF Dimethyl Acetal: Direct Access to 4´-Alkoxy-2´,3´-didehydro-2´,3´-dideoxynucleosides
- Synthesis, structure-activity relationship studies, and X-ray crystallographic analysis of arylsulfonamides as potent carbonic anhydrase inhibitors
- Backbone resonance assignments of human cytosolic dNT-1 nucleotidase
- Conformationally constrained nucleoside phosphonic acids - potent inhibitors of human mitochondrial and cytosolic 5'(3')-nucleotidases
|
| is http://linked.open...vavai/cep/projekt
of | |
![[RDF Data]](/fct/images/sw-rdf-blue.png)
![[cxml]](/fct/images/cxml_doc.png)
![[csv]](/fct/images/csv_doc.png)
![[text]](/fct/images/ntriples_doc.png)
![[turtle]](/fct/images/n3turtle_doc.png)
![[ld+json]](/fct/images/jsonld_doc.png)
![[rdf+json]](/fct/images/json_doc.png)
![[rdf+xml]](/fct/images/xml_doc.png)
![[atom+xml]](/fct/images/atom_doc.png)
![[html]](/fct/images/html_doc.png)