Glycosidases in Carbohydrate Synthesis: When Organic Chemistry Falls Short

Thanks to the stability, good availability, stereoselectivity and broad substrate specificity, oligosaccharide synthesis catalyzed by glycosidases represents an elegant way to complex carbohydrate structures. Two approaches to glycosidase catalysis are presented: i) the use of structurally modified substrates that carry various functional moieties in the molecule, and ii) the design of mutant glycosidases void of hydrolytic activity. Products of glycosidase-catalyzed synthesis are applicable in a range of are as such as immunology, therapy of Alzheimer's or Parkinson's diseases and the synthesis of neoglycoproteins

Modified Substrates in β-N-Acetylhexosaminidase-Catalyzed Synthesis

4 Conclrrsion 4 CoNcrusroN This Ph. D. thesis is a systematic study of the substrate specificity and the synthetic potential of B-N-acetylhexosaminidases (EC 3.2.1.52) with structurally modified substrates. It comprises four publications in intemational journals, one review and 17 oral and poster contributions. The following parts of the substrate molecule were modified: 2-acetamido moiety, the C-6 hydroxyl (oxidations, introduction of a cyano group) and the aglycon part (glycosyl azides - C-N bond hydrolysis). Thirteen modified substrates were synthesized, seven of them were described for the first time. They were tested for hydrolysis and transglycosylation by over thirty fungal -N-acetylhexosaminidases (culture collections at Charles University and at the Institute of Microbiology, Academy of Sciences of the Czech Republic) and the results were discussed in relation to the conclusions of molecular modeling (B-N-acetylhexosaminidase from Aspergillus oryzae CCF 1066). Eight oligosaccharidic structures (six of them novel) were prepared by semi- preparative transglycosylation reactions (tens of miligrams), isolated (mostly 16_377a yields, even 787o yie\ď) and fully characterized. Noteworthy properties like immunoactivity (binding to natural killer cell activation receptors) and inhibitory potential were...4 Conclrrsion 4 CoNcrusroN This Ph. D. thesis is a systematic study of the substrate specificity and the synthetic potential of B-N-acetylhexosaminidases (EC 3.2.1.52) with structurally modified substrates. It comprises four publications in intemational journals, one review and 17 oral and poster contributions. The following parts of the substrate molecule were modified: 2-acetamido moiety, the C-6 hydroxyl (oxidations, introduction of a cyano group) and the aglycon part (glycosyl azides - C-N bond hydrolysis). Thirteen modified substrates were synthesized, seven of them were described for the first time. They were tested for hydrolysis and transglycosylation by over thirty fungal -N-acetylhexosaminidases (culture collections at Charles University and at the Institute of Microbiology, Academy of Sciences of the Czech Republic) and the results were discussed in relation to the conclusions of molecular modeling (B-N-acetylhexosaminidase from Aspergillus oryzae CCF 1066). Eight oligosaccharidic structures (six of them novel) were prepared by semi- preparative transglycosylation reactions (tens of miligrams), isolated (mostly 16_377a yields, even 787o yie\ď) and fully characterized. Noteworthy properties like immunoactivity (binding to natural killer cell activation receptors) and inhibitory potential were...Department of BiochemistryKatedra biochemieFaculty of SciencePřírodovědecká fakult

История и перспективы применения железобетона

Строительство из бетона и железобетона по праву можно назвать самым перспективным из существующих технологий возведения зданий. «Бетон – наилучший из материалов, изобретенных человечеством», – сказал знаменитый итальянский архитектор П.Л. Нерви. И он был прав. Сегодня большинство домов в современных городах сделано из бетона. Он применяется для строительства мостов, портов и плотин, дорог, подземных сооружений, атомных электростанций и стартовых площадок для ракет

Выбор параметров установок продольной и поперечной компенсаций дальних электропередач с промежуточными системами

Приведены аналитические выражения по определению компенсирующих устройств дальних электропередач в зависимости от места присоединения ПС (к вводу или выводу установок продольной емкостной компенсации) с учетом предельности режима

Comparison of experimental results from three dual fluidized bed test facilities capturing CO2 with CaO

10th International Conference on Greenhouse Gas Control Technologies[EN] Postcombustion CO2 capture technologies using CaO as a regenerable solid sorbent have emerged as a promising route to reduce the electricity penalty and the cost of CO2 capture from flue gases of both new and existing fossil fuelled power plants. Rapid progress is taking place in the understanding of these processes at different levels. However, experimental information, validating the concept under continuous operating conditions similar to those expected for large-scale application, remain scarce. We present here a comparative analysis of the results obtained in three laboratory-scale dual fluidized bed (DFB) test facilities in Spain, Germany and Canada. The test facilities range from 10 to 75 kWth with riser heights between 4.5 and 12.4 m. They have been operated to capture CO2 with CaO from simulated flue gases in the bubbling, turbulent and fast fluidization fluid-dynamic regimes. The carbonator reactors are interconnected with regenerators, where the CaCO3 decomposition has been conducted continuously and semi-continuously, operated in both air-combustion and oxy-combustion modes. Many stationary and non-stationary states have been achieved at different combinations of the key operating parameters (e.g. calcium looping ratio). All DFB test facilities showed a carbon balance closure of high quality in most tests. The trends of CO2 capture efficiency with respect to operating conditions and sorbent characteristics are compared and a discussion is made on the most appropriate methodology to conduct future tests under a joint new FP7 project (CaOling) that aims at the rapid scaling up of the calcium looping technology.This work is being funded by the European Commision 7th Framework Programme under the CaOling Project.Peer reviewe

Discovery of human hexosaminidase inhibitors by in situ screening of a library of mono- and divalent pyrrolidine iminosugars

Two libraries of mono- and dimeric pyrrolidine iminosugars were synthesized by CuAAC and (thio)urea-bond-forming reactions from the respective azido/aminohexylpyrrolidine iminosugar precursors. The resulting monomeric and dimeric compounds were screened for inhibition of β-N-acetylglucosaminidase from Jack beans, the plant ortholog of human lysosomal hexosaminidases. A selection of the best inhibitors of these libraries was then evaluated against human lysosomal β-N-acetylhexosaminidase B (hHexB) and human nucleocytoplasmic β-N-acetylglucosaminidase (hOGA). This evaluation identified a potent (nM) and selective monomeric inhibitor of hOGA (compound 7A) that showed a 6770-fold higher affinity for this enzyme than for hHexB. The corresponding dimeric derivative (compound 9D) further remarkably improved the selectivity in the inhibition of hOGA (2.7 × 104 times more selective for hOGA over hHexB) and the inhibition potency (by one order of magnitude). Docking studies were performed to explain the selectivity of inhibition observed in compound 7A.Ministerio de Ciencia e Innovación PID2020-116460RB-100Ministerio de Economía y Competitividad CTQ2016-77270-RConsejería de Economía y Conocimiento. Junta de Andalucía FQM-345Czech Science Foundation GA21-01948

ChemInform Abstract: Glycosidases in Carbohydrate Synthesis: When Organic Chemistry Falls Short

Thanks to the stability, good availability, stereoselectivity and broad substrate specificity, oligosaccharide synthesis catalyzed by glycosidases represents an elegant way to complex carbohydrate structures. Two approaches to glycosidase catalysis are presented: i) the use of structurally modified substrates that carry various functional moieties in the molecule, and ii) the design of mutant glycosidases void of hydrolytic activity. Products of glycosidase-catalyzed synthesis are applicable in a range of are as such as immunology, therapy of Alzheimer's or Parkinson's diseases and the synthesis of neoglycoproteins

Biocatalysis: “A Jack of all Trades...”

Biotransformation has accompanied mankind since the Neolithic community, when people settled down and began to engage in agriculture [...