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Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Modified nucleotides for selection of functional nucleic acids and labelled probes for chemical biology
Granting Departments: |
Department of Chemistry of Natural Compounds
Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i. |
Study Programme/Specialization: | Biochemistry and Bioorganic Chemistry ( in English language ) |
Supervisor: | prof. Ing. Michal Hocek, DSc. |
Annotation
We will design and synthesize modified nucleoside triphosphates bearing diverse functional groups for enzymatic synthesis of modified oligonucleotides which will be applied in selection and construction of new functional nucleic acids, e.g. aptamers or aptazymes and for the construction of fluorescent or redox probes for applications in chemical biology. References: 1. Hocek, M.: "Enzymatic Synthesis of Base-Functionalized Nucleic Acids for Sensing, Cross-linking, and Modulation of Protein–DNA Binding and Transcription" Acc. Chem. Res. 2019, 52, 1730-1737. 2. Micura, R.; Höbartner, C. Fundamental studies of functional nucleic acids: aptamers, riboswitches, ribozymes and DNAzymes. Chem. Soc. Rev. 2020, 49, 7331–7353.
Contact supervisor
Study place:
Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
New cytostatic nucleosides and nucleotides with new mechanisms of action
Granting Departments: |
Department of Chemistry of Natural Compounds
Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i. |
Study Programme/Specialization: | Biochemistry and Bioorganic Chemistry ( in English language ) |
Supervisor: | prof. Ing. Michal Hocek, DSc. |
Annotation
We will design and synthesize new modified nucleosides and nucleotides as potential cytostatic agents with new mechanisms of action which includes modulation of receptors or activation of cytostatic proteins. Selected active compounds will be further optimized in order to identify preclinical drug candidates. References: 1. Jordheim, L. P.; Durantel, D.; Zoulim, F.; Dumontet, C. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat. Rev. Drug Discov. 2013, 12, 447–464. 2. Perlíková, P.; Hocek, M. Pyrrolo[2,3-d]pyrimidine (7-deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides. Med. Res. Rev. 2017, 37, 1429–1460.
Contact supervisor
Study place:
Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Preparation and applications of charged heterodienes in bioorthogonal reactions
Granting Departments: |
Department of Chemistry of Natural Compounds
Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i. |
Study Programme/Specialization: | Biochemistry and Bioorganic Chemistry ( in English language ) |
Supervisor: | Ing. Milan Vrábel, Ph.D. |
Annotation
Our group recently described the development and first applications of N1-alkyl-1,2,4-triazinium salts in bioorthogonal reactions (Angew. Chem. Int. Ed., 2023, e202306828). In this project, we want to explore the chemistry of these charged heterodienes in more detail. In addition, we want to apply the developed reagents in applications ranging from selective modification of biomolecules to cellular applications (e.g. bioimaging). The project combines synthetic organic chemistry, reaction kinetics and stability studies with biological experiments that will be performed mainly in collaboration with biologists in the group.
Contact supervisor
Study place:
Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Sequence-specific enzymatic synthesis of base-modified RNA
Granting Departments: |
Department of Chemistry of Natural Compounds
Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i. |
Study Programme/Specialization: | Biochemistry and Bioorganic Chemistry ( in English language ) |
Supervisor: | prof. Ing. Michal Hocek, DSc. |
Annotation
We will design and synthesize modified ribonucleoside triphosphates bearing diverse functional groups at nucleobase. These nucleotides will be used for sequence-specific enzymatic synthesis of oligoribonucleotides (RNA) bearing labels or modifications at specific positions using engineered DNA polymerases. The applications will include tRNA, mRNA, sgRNA etc. References: 1. Micura, R.; Höbartner, C. Fundamental studies of functional nucleic acids: aptamers, riboswitches, ribozymes and DNAzymes. Chem. Soc. Rev. 2020, 49, 7331–7353. 2. Milisavljevic, N.; Perlíková, P.; Pohl, R.; Hocek, M. Enzymatic synthesis of base-modified RNA by T7 RNA polymerase. A systematic study and comparison of 5-substituted pyrimidine and 7-substituted 7-deazapurine nucleoside triphosphates as substrates. Org. Biomol. Chem. 2018, 16, 5800-5807.
Contact supervisor
Study place:
Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Updated: 25.3.2022 16:19, Author: Jan Kříž