Novel types of modified derivatives and analogues of nucleobases, nucleosides, nucleotides and nucleic acids are designed and prepared for applications in all areas of biomedicinal sciences (medicinal chemistry, biochemistry, chemical biology, bioanalysis etc.).
Basic developments of methodology for the synthesis of these modified biomolecules are performed largely using modern methods (including metal- or enzyme-catalyzed reactions). Biological activity (cytostatic, antiviral etc.) of the novel nucleobases, nucleosides and nucleotides is systematically studied in collaboration with several groups both in academia and in pharmaceutical industry. Several collaborative projects also address chemical biology of nucleic acids (i.e. DNA polymerase specificity and fidelity). Functionalized nucleic acids bearing diverse interesting and useful substituents are another goal of our group. For details, see Projects.
Panattoni, A. et al: "Flexible Alkyne-Linked Thymidine Phosphoramidites and Triphosphates for Chemical or Polymerase Synthesis and Fast Post-Synthetic DNA Functionalization through CuAAC" Org. Lett. 2018, in press, doi: 10.1021/acs.orglett.8b01533.
Krömer, M. et al: "Synthesis of dihydroxyalkynyl and dihydroxyalkyl nucleotides as building blocks or precursors for introduction of diol or aldehyde functions to DNA for bioconjugations" Chem. Eur. J. 2018, in press, doi: 10.1002/chem.201802282.
Slavíčková, M. et al: "Turning off transcription with bacterial RNA polymerase through CuAAC click reactions of DNA containing 5-ethynyluracil" Chem. Eur. J. 2018, 24, 8311-8314.