National Repository of Grey Literature 30 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Multivalent carbohydrate ligands of galectins
Hovorková, Michaela ; Křen, Vladimír (advisor) ; Kavan, Daniel (referee)
Galectins are proteins, wich belong to a group of lectins that are able to bind to saccharide units and they specifically recognize glycans exposed to the surface of the cells. Galectins participate in vivo, for example, in carcinogenesis, angiogenesis or fibrosis. Their occurrence increases significantly in connection with a number of pathogenic processes, therefore they can be used as markers for some types of cancer or cardiopathology and also for the targeted binding of therapeutics and/ or imaging agents in diagnosis and therapy. Galectin-3 has a specific structure known as chimeric and it is capable of forming multivalent oligomers. The natural ligands of galectins are glycans containing terminal β-galactosides, especially N-acetyllactosamine, but the binding of monovalent glycans is very weak. Glycoconjugates with high affinity to galectin receptors are optimally multivalent, biocompatible and stable in vivo. These criteria accomplish carbohydrate ligands conjugated to soluble and structurally flexible N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. In this work two types of functionalized disaccharides based on N-acetyllactosamine (Galβ4GlcNAc) and its structural analogue of N,N'-diacetyllactosamine (GalNAcβ4GlcNAc) was prepared by enzymatic synthesis. For the synthesis were used...
Differences in Oxidation Mechanism of Selected Bioflavonoids, UV-Vis and IR Spectroelectrochemical Study
Sokolová, Romana ; Fiedler, Jan ; Ramešová, Šárka ; Kocábová, Jana ; Degano, I. ; Quinto, A. ; Křen, Vladimír
The oxidation of selected bioflavonoids (quercetin, rhamnazin, fisetin, rhamnetin, taxifolin, luteolin, silybin and 2,3-dehydrosilybin) was studied by electrochemical and spectroscopic methods. The oxidation mechanism and formation of oxidation products depends on the chemical structure. Only small differences in the chemical structure of compounds with flavone, flavanone and flavonol motif result in extremely variable oxidation pathways and products. Products of oxidation and further decomposition were determined by HPLC-ESIMS/MS and HPLC-DAD.
Modified Substrates in β-N-Acetylhexosaminidase-Catalyzed Synthesis
Bojarová, Pavla ; Křen, Vladimír (advisor) ; Moravcová, Jitka (referee) ; Walterová, Daniela (referee)
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...
New Microbial Glycosidases
Charvátová, Andrea ; Křen, Vladimír (advisor) ; Králová, Blanka (referee) ; Walterová, Daniela (referee)
Sunrvranv Glycosidases from fungi are useful in the preparation of various glycosides mainly by transglycosylation or reversed glycosylation. The lack ofany requirement for protection- deprotection sequences, mild conditions and easier synthesis of thermodynamically not preferred glycosidic bonds are the main advantages of glycosidase-catalysed synthesis of glycosides. In ttris thesis we concentratedon exoglycosidases,mainly B.N.aceýlhexosaminidases, cr-galactosidases and cr-L-rhamnosidases. For the enzyme preparation taxonomically characterised fungal strains from public collections were used. A library comprising more than 200 various glycosidases was developed by modification ofcultivation conditions and by the use ofspecific inducers. The enrymes were used for screening ofsubstrate specificity and stability in organic solvents and subsequently for synthesis and modification of various substrates. Both B-N-acetylgalactosaminidase and B-N-acetylglucosaminidase activities in the series of B-N-acetylhexosaminidases were determined. Saccharides with strong immunomodulation activity $-o-GalpNAc-(i-+4)-o-GlcpNAc and B-o-GalpNAc-(1-+6)-o-GlcpNAc were synthesisedby transglycosylation using B-N-acetylhexosaminidase from Penicillium oxalicum CCF 2430' enryme having the highest B.N-acetylgalactosaminidase activiý....
Development of new glycosylation methods for the synthesis of nucleosides
Downey, Alan Michael ; Hocek, Michal (advisor) ; Křen, Vladimír (referee) ; Kočovský, Pavel (referee)
As they make up DNA and RNA, nucleosides are considered the key to life. Synthetic nucleosides also constitute many drugs that treat viral infections and cancer. As a result, more efficient methods to access these crucial molecules would have implications that extend beyond a synthetic chemist's benchtop and into medicinal chemistry and medical research. One of the most challenging steps in the synthesis of nucleosides is the glycosylation step between the acceptor heterocycle (nucleobase) and the saccharide-based donor. Often to obtain satisfactory yield of this step with good regio- and stereochemical control the extensive use of protecting groups must be employed to squelch reactivity at unwanted reactive groups. Consequently, this process of protection−glycosylation−deprotection is laborious, inefficient, and often requires the use of toxic reagents. It would be, therefore, highly welcomed if new methodology to effect this glycosylation step was designed that reduces or removes the need to use protecting groups, but would still provide nucleosides in good yield, regio- and stereoselectively. Herein, this thesis presents my efforts into achieving this end. By employing modified Mitsunobu conditions, I determined that it is possible to directly glycosylate a nucleobase with D-ribose to afford...
Enzymatic and Metabolic Transformation of Silybin and its Congeners
Purchartová, Kateřina ; Křen, Vladimír (advisor) ; Macek, Tomáš (referee) ; Vítek, Libor (referee)
Natural flavonoids and flavonolignans feature beneficial properties for living organisms such as antioxidant and hepatoprotective effects, anticancer, chemoprotective, dermatoprotective and hypocholesterolemic activities. Their metabolism in mammals is complex, the exact structure of their metabolites still remains partly unclear and the standards are usually not commercially available. Hence, this project focused on the preparation of potential and defined biotransformation Phase II sulfated metabolites of silymarin flavonolignans: silybin, 2,3-dehydrosilybin, isosilybin, silychristin, silydianin and flavonoids quercetin, taxifolin, rutin and isoquercitrin. Pure sulfated derivatives were prepared using aryl sulfotransferase from Desulfitobacterium hafniense and aryl sulfotransferase from rat liver. Using heterologously expressed PAPS (3'-phosphoadenosine-5'-phosophosulfate) - independent arylsulfotransferase from Desulfitobacterium hafniense and cheap p-nitrophenyl sulfate as sulfate donor, sulfated flavonolignans and flavonoids were obtained in high yields. Silymarin flavonolignans afforded exclusively monosulfates at the position C-20 (C-19 in the case of silychristin), except 2,3-dehydrosilybin that yielded also the 7,20-O-disulfated derivative. Isoquercitrin and rutin were selectively sulfated...
Mammalian Serine Racemase as a Pharmaceutical Terget
Vaníčková, Jana ; Konvalinka, Jan (advisor) ; Kotora, Martin (referee) ; Křen, Vladimír (referee)
PH.D. DISSERTATION Mammalian Serine Racemase as a Pharmaceutical Target Jana Jirásková Supervisor: Jan Konvalinka Department of Biochemistry Faculty of Science Charles University Institute of Organic Chemistry and Biochemistry Gilead Sciences & IOCB Research Centre Academy of Sciences of the Czech Republic Praha 2010 Introduction Serine racemase is a pyridoxal-5'-phosphate (PLP) -dependent enzyme that is responsible for D- serine production. D-serine is a neurotransmitter that acts, together with L-glutamate, as agonist of ionotropic N-methyl-D-aspartate (NMDA) receptors, which are important for neuronal tissue signalization. Recent serine racemase knock-out mouse studies revealed that SR produces approximately 90% of brain D-serine. SR was first isolated from a pool of rat brains about a decade ago. Its orthologs are present in mammals as well as plants and yeast. Mammalian SRs share high sequence identity, about 90%. Mouse and human SRs are similar enzymatically, suggesting that mouse SR and mouse model are suitable to shed light on human SR. SR forms homodimers in solution and has a molecular weight of approximately 37 kDa per monomer. In addition to pyridoxal-5'-phosphate, the enzyme requires divalent cations such as Ca2+ or Mg2+ , nucleotides such as ATP, and reducing agents for full activity. The...

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