CARBOSILANE DENDRIMERS AND NOVELDENDRITIC ARCHITECTURES
In our research group we are developing new concepts and the corresponding synthetic methods for the preparation of materials which show desirable biological activity, provide for bio-medicinal diagnostics or, as in the case of theranostics, combine both functions. Multivalency is …
Our research interest focuses on:
• carbosilane dendrimers
We develop synthetic methods to prepare multivalent carbosilane structures (dendrimers, dendrons, amfifiles, etc.) It has been proved that phosphonium terminated carbosilane dendrimers developed in our laboratories form complexes with therapeutic sequences of nucleic acids (dendriplexes); and, compared to commonly used ammonium analogs, they have lower cytotoxicity and higher transfection efficacy. A modification of a phosphonium dendron with a non-polar carbohydrate chain in the focal point leads to amphiphilic molecules, which form various supramolecular assemblies (micelles, liposomes, etc.). Therefore, such compounds open new opportunities in gene therapies and biomedical applications. Furthermore, applications of multivalent and branched compounds offer solutions in the field of catalysis. We develop highly efficient catalytic systems, optimize reaction conditions and subsequent processes to maximize a general sustainability of the catalytic reactions.
• branched and dendritic modules
Carbohydrates, apart from serving as biomolecules for storage and transport of energy, are also involved in critical cellular processes such as bacterial and viral infection, immune response, tumor development and metastasis, cell signaling, embryonic development and many others. Carbohydrates and glycostructures obtained by chemical synthesis are indispensable tools to elucidate molecular basis of these processes.
Our research interest focuses on:
• fluorinated carbohydrates
Fluorinated carbohydrates continue to attract attention of synthetic chemists and glycobiologists. Introduction of fluorine into carbohydrates modifies their stereoelectronic, lipophilic, steric, and hydrogen-bonding properties. These modifications in turn lead to alterations of their interactions with proteins and other biomolecules or to a greater metabolic stability in comparison with the parent carbohydrates. Fluorinated sugars are used, for example, as probes in studies of enzyme – carbohydrate, and lectin – carbohydrate interactions, inhibitors of carbohydrate processing enzymes, chemical agents used for modification of the cellular glycome, model compounds for the study of fluorine hydrogen bonding, or components of anticancer vaccines.
• Stereoselectivity in Glycosylation with Deoxofluorinated Glucosazide and Galactosazide Thiodonors, J. Org. Chem.2019, 84(10), 6405-6431. https://doi.org/10.1021/acs.joc.9b00705
• Synthesis and in Vitro Cytotoxicity of Acetylated 3-Fluoro, 4-Fluoro and 3,4-Difluoro Analogs of D-glucosamine and D-galactosamine, Beilstein J. Org. Chem. 2016, 12, 750-759. http://dx.doi.org/10.3762/bjoc.12.75
• A Convenient Route to Peracetylated 3-Deoxy-3-fluoro Analogues of D-Glucosamine and D-Galactosamine from a Černý Epoxide, Synlett 2014, 25, 1253-1256. http://dx.doi.org/10.1055%2Fs-0033-1341187
• Skeletal Rearrangements Resulting from Reactions of 1,6:2,3- and 1,6:3,4-Dianhydro-β-D-hexopyranoses with Diethylaminosulphur trifluoride, Org. Biomol. Chem. 2012, 10, 394-403. http://dx.doi.org/10.1039%2FC1OB06336G
• Synthesis of All Configurational Isomers of 1,6-Anhydro-2,3,4-trideoxy-2,3-epimino-4-fluoro-β-D-hexopyranoses, J. Org. Chem. 2010, 75, 3443-3446. http://dx.doi.org/10.1021%2Fjo1000912
• antitumor carbohydrate-modified organocomplexes
Antitumor carbohydrate-modified organocomplexes. The landmark discovery of the antitumor properties of cisplatin initiated research into antitumor properties of organometallic and coordination complexes. Modification of antitumor metallocomplexes by attaching of a carbohydrate moiety can reduce toxicity, improve solubility, and modulate hydrolytic stability and biocompatibility of the resulting conjugate. Moreover, increased uptake of sugars by cancer cells and specific roles of carbohydrates in cancer growth and progression can result in higher selectivity for cancer cells or new mechanisms of action in comparison with unmodified complexes.
• Improving Cytotoxic Properties of Ferrocenes by Incorporation of Saturated N-heterocycles, J. Organomet. Chem. 2017, 846, 141-151. https://doi.org/10.1016/j.jorganchem.2017.06.005
• Electrochemical Analysis of a Novel Ferrocene Derivative as a Potential Antitumor Drug, Analyst 2015, 140, 5864-5867. https://doi.org/10.1039/c5an00958h
• Evaluation of Cytotoxic Activity of Titanocene Difluorides and Determination of Their Mechanism of Action in Ovarian Cancer Cells, R. Invest. New Drugs 2015, 33, 1123-1132. https://doi.org/10.1007/s10637-015-0274-y
• Titanocene Dihalides and Ferrocenes Bearing a Pendant α-D-Xylofuranos-5-yl or α-D-Ribofuranos-5-yl Moiety. Synthesis, Characterization, and Cytotoxic Activity, Organometallics 2014, 33, 2059-2070. https://doi.org/10.1021/om500200r
Multivalency is a common principle to increase the affinity and specificity of ligand–receptor interactions in nature and results in a cooperative, over‐additive enhancement of binding affinity. Synthetic multivalent carbohydrates, especially well defined glycodendrimers, represent efficient tool for study of glycobiological processes in living systems, which are important in various processes. Currently, we are the only groups developing carbosilane glucodendrimers (glyco-CS-DDMs) as class of well-defined functional bionanomaterials.