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Aminokwasy, glikany, peptydy i białka w ścieżkach diagnostycznych i terapeutycznych chorób cywilizacyjnych XXI wieku : projektowanie i charakterystyka fizykochemiczna oraz strukturalna

Bylińska Irena, Dzierżyńska Maria, Giżyńska Małgorzata, Guzow Katarzyna, Jankowska Elżbieta, Jurczak Przemysław, Kaczyński Zbigniew, Karska Natalia, Kowalczyk Agnieszka, Kuncewicz Katarzyna, Orlikowska Marta, Sawicka Justyna, Spodzieja Marta, Szpakowska Nikola, Szymańska Aneta, Wieczerzak Ewa, Witkowska Julia, Rodziewicz-Motowidło Sylwia

Wiadomości Chemiczne

2022

[Z] 76, 5-6

393--431

The civilization diseases of the 21st century are non-infectious disorders, affecting a large part of modern society. They are associated with the significant development of industry and technology, and hence with environmental pollution and an unhealthy lifestyle. These factors have led to the development of many civilization diseases, which currently include: cardiovascular diseases, respiratory diseases, diabetes, obesity, malignant tumors, gastrointestinal diseases, mental disorders and allergic diseases. The development of technologies, including modern therapies and new drugs, resulted in increase in life expectancy. This creates a global problem of an aging population with an increasing number of diseases of the old age, i.e. dementias. In addition, sedentary lifestyles and changing diets are the reasons why more and more people develop metabolic diseases, as well as neurological and cognitive disorders characterized by progressive damage to nerve cells and dementia. Currently, problem on a global scale is also the growing resistance to existing antimicrobial drugs. Therefore, the scientists face many challenges related to searching for the causes of these diseases, their diagnosis and treatment. Scientific research conducted at the Department of Biomedical Chemistry at the Faculty of Chemistry of the University of Gdańsk is part of this research trend. In this publication, we discuss various research topics with the long-term aim of solving the problems associated with the diseases mentioned above. The following chapters are dedicated to (i) looking for new effective fluorophores with diagnostic and anti-cancer activity; (ii) designing of new compounds with antibacterial and antiviral activity and their synthesis; (iii) investigating the mechanisms of amyloid deposit formation by human cystatin C and possibilities of inhibition of this process; (iv) designing and studies of compounds activating the proteasome with the potential to suppress the development of neurodegenerative diseases; (v) designing peptide fibrils and hydrogels as drug carriers; (vi) searching for peptide inhibitors of immune checkpoint as potential drugs for immunotherapy; (vii) studying the mechanism of action of selected herpesviruses by determining the structure of viral proteins and (viii) studying the composition of natural glycans and glycoconjugates in order to better understand the mechanisms of interaction of bacteria with the environment or with the host.

Engineered atenolol-glycoconjugates to target H9c2 cardiomyocyte cell lines

Kumbha Smita Tukaram, Bhatia Manish Sudesh, Patil Shitalkumar Shivgonda

Acta Innovations

2022

no. 43

36--43

Background: One of the most important fields of biomedical engineering study nowadays is targeted drug delivery to specific cells. A drug's therapeutic efficacy can be improved and optimised by tightly targeting it to a pathophysiologically essential tissue architecture. The goal of this research is to develop saccharide conjugates for the targeted delivery of Atenolol, a -blocker. Methods: Galactose (monosaccharide), pectin (polysaccharide), and chitosan were chosen as the saccharides (polysaccharide). By grafting Atenolol with the modified saccharides, the conjugates were created. Spectroscopic and thermal studies were used to describe the chemically changed saccharides conjugates. H9c2 cell lines were used to conduct drug release research and cellular uptake studies. To investigate cytotoxicity, a brine shrimp lethality test was done. Results: The outcomes exhibit that Atenolol-modified saccharide conjugates can productively convey the medication to the target. Conclusion: It can be inferred that the improvement of saccharide-drug conjugates can be a compelling methodology for targeting cardiovascular medication.

Synteza i zastosowanie nowych katalizatorów metatezy olefin

Hryniewicka A.

Wiadomości Chemiczne

2014

[Z] 68, 11-12

961--980

Olefin metathesis has emerged as a powerful tool for the formation of carboncarbon double bonds. The success of this methodology has spurred the intense investigation of new catalysts showing a better application profile. The syntheses and the application profiles of the seven new ruthenium metathesis catalysts have been described. Five of them were modified in benzylidene part with 6-hydroxychromane- and 2H-3,4-chromenemethylidene moiety. In chromanol – α-tocopherol model compound, some specific stereoelectronic effects have been observed. Introduction of this ligand to the catalyst may provide new advantageous properties. The other new catalysts contained modified N-heterocyclic carbene ligand (NHC), in which N,N’-mesityl substituents of NHC system were linked with diethylene glycol chain as a “clamping ring”. This ring would contribute to a steric shield of the NHC and ruthenium coordination center. Probably it may inforce a proper orientation of substituents in metallacyclobutane (all-cis), leading to Z-olefin formation. The obtained catalysts were investigated in model reactions: ring closing metathesis, cross metathesis and enyne metathesis. The experiments proved they efficiency. In many reactions the catalysts showed activity comparable or superior to that of commercially available Grubbs and Hoveyda 2nd generation complexes. Stereochemistry Z/E of the cross-metathesis products obtained using new and known complexes were similar as well. The catalysts were applied in the synthesis of a new type of α-tocopherol glycoconjugates. An efficient method of the synthesis Hoveyda 2nd type complexes starting from ruthenium trichloride was developed. It is possible to circumvent using special laboratory equipment and expensive reagents. Hoveyda type complexes can be achieved with very good yield in gram scale. Keywords: