First project period, Feb. 1st, 2021 to Jan. 31st, 2022 (12 months)
The project proposal is grounded on the iterative research, starting with the synthesis and delivery of the genZ SBBs. Our SBBs are constructed by optimized procedures of grafting three (or four) nitrogen-containing (methylimidazole, pyridine or amine) coordination arms to one rim of the macrocycle. The opposite rim contains six (in the case of calixarenes) or four (in the case of resorcinarenes) “legs” (C5-alkyl, tBu, amino, ammonium-containing, pyridinium-containing, OMe or their combinations). These unmodified SBBs make up the generation Zero (genZ) set of the SBBs. The delivered genZ SBBs set will be subjected to the recognition and binding studies on a suitable set of polynucleotides/oligonucleotides, as well as to biological assays in living systems (human cell lines). Based on these results, most promising binding candidates within the genZ SBBs set will be subjected to single crystal XRD studies. During the first project period, a PostDoc researcher and a PhD student shall join the team.
Second project period, Feb. 1st, 2022 to Jul. 31st, 2023 (18 months)
Second project period will be marked by the research on gen1 SBBs set. This set will be formed by grafting fluorophoric amino acids to the calixarene/resorcinarene scaffolds of the best binders identified within the genZ SBBs set through the series of experiments conducted over the first project period. Based on the results of this research, the most intriguing gen1 SBB – oligonucleotides assemblages will be subjected to the XRD structural studies.
During the second project period, PhD student will be mostly mastering syntheses of the SBBs (including grafting of the fluorophoric amino acids to their scaffolds). PostDoc researcher will continue its work on the binding studies and crystallization assays, and conclude its engagement with the end of the second project period.
Third project period, Aug. 1st, 2023 to Jan. 31st, 2025 (18 months)
Results of the binding studies, biological assays and structural studies on the gen1 SBBs set will guide the design and synthesis of the final set – gen2 SBBs set, which will be prepared, delivered, biochemically and structurally characterized during the third project period. The third period will be, hence, marked by a final research iteration, in the frame of which, fluorophoric SBBs from the gen1, will be fine-tuned to come up with a set of the relevant binders prone to a wide set of applicative purposes.
During this period, the PhD student will conclude the practical research and finish writing the PhD thesis.