3 research outputs found
Design and synthesis of 3-O-substituted galactose derivatives as galectin-8 ligands
Galektin-8 je član družine lektinov, proteinov s posebno afiniteto za ß-galaktozide, ki se nahaja tako v normalnih kot v tumorskih celicah. Vključen je v širok spekter celičnih odzivov, kot so celična adhezija, zaustavitev rasti, apoptoza, prepoznavanje patogenov, avtofagija in imunosupresija. Ker lahko izražanje galektina-8 pozitivno ali negativno korelira z napredovanjem ali ponovitvijo tumorja, bi merjenje njegove ravni v prihodnosti lahko služilo odkrivanju raka, kot tudi napovedovanju prognoze bolezni in terapevtske učinkovitosti.
Zaradi vključenosti galektinov v številne celične procese in njihove vloge v patologiji številnih bolezni se je razvila potreba po odkritju njihovih antagonistov. Kljub prizadevanjem številnih raziskovalcev po vsem svetu ostaja to področje, sploh kar se tiče galektina-8, precej neraziskano, nabor že znanih antagonistov pa je posledično precej ozek.
V okviru magistrske naloge smo z uporabo organokositrovih spojin regioselektivno alkilirali metil ß-D-galaktozo, in tako sintetizirali nove potencialne ligande galektina-8, pri načrtovanju le-teh pa smo se opirali na strukturo pred kratkim objavljenega liganda in kristalno strukturo galektina-8. Vsem sintetiziranim spojinam je skupen metil ß-D-galaktozni del molekule, razlikujejo pa se v substituentu na mestu 3. Sintezni postopki z uporabo dibutilkositrovega diklorida kljub nekaterim modifikacijam metode večinoma niso bili uspešni, zato smo spremenili celoten postopek in kot katalizator uporabili dibutilkositrov oksid. Čeprav smo pri sintezi naleteli na številne težave, smo uspešno sintetizirali 7 končnih spojin. Tekom magistrske naloge smo tako vzpostavili in optimizirali sintezni postopek, ki je splošno uporaben tudi za nadaljnjo sintezo 3-O-substituiranih derivatov metil ß-D-galaktoze. Končne spojine sicer presenetljivo niso izkazale vezave na protein, a so vseeno prispevale k boljšemu razumevanju odnosa med strukturo in delovanjem ligandov galektina-8.Galectin-8 is a member of the family of lectins, proteins possessing special affinity for β-galactoside, which is detected both in normal and in tumor cells. It is involved in a wide range of cellular responses, such as cellular adhesion, growth arrest, apoptosis, pathogen recognition, autophagy and immunosuppression. Since galectin-8 expression can positively or negatively correlate with tumor progression or recurrence, measuring its level in the future could serve to detect cancer, as well as predict the prognosis of the disease and therapeutic efficacy.
Due to the involvement of galectins in many cellular processes and their role in the pathology of many diseases, the need for the discovery of their antagonists has developed. Despite the efforts of many researchers this area remains, in particular regarding galectin-8, rather unexplored, and the number of known antagonists is consequently rather limited.
Within this Master\u27s thesis, we synthesized novel galectin-8 ligands by regioselective alkylation of methyl-β-D-galactopyranoside using organotin compounds. Their design was based on the structure of a recently reported ligand and the crystal structure of galectin-8. All synthesized compounds carry the methyl β-D-galactopyranoside fragment, but differ in the substituent at position 3. Synthetic procedures using dibutyltin dichloride were largely unsuccessful despite some modifications to the method, therefore another catalyst, dibutyltin oxide, was used instead. Although we encountered many problems during the synthesis, we successfully synthesized 7 end compounds. During the Master\u27s thesis, we established and optimized the synthetic procedure, which can be used for further syntheses of 3-O-substituted methyl-β-galactopyranoside derivatives. Surprisingly, our compounds did not exhibit any binding to the protein, nevertheless they provided a better understanding of the structure-activity relationship of galectin-8 ligands
Magnetic nanoparticles in 3D-printed scaffolds for biomedical applications
Magnetic nanoparticles (MNPs) have recently attracted considerable attention, mainly due to their unique magnetic properties and biocompatibility. Although MNPs have been extensively studied for biomedical applications, there are still very few studies on them as part of three-dimensional (3D)-printed scaffolds. Thus, this review aims to show the potential of MNPs to modulate various properties of 3D-printed scaffolds. 3D Printing is for itself a contemporary method in biomedicine, owing to its ability to produce versatile scaffolds with complex shapes enabling a homogeneous distribution of cells or other entrapped compounds, as well as possible precise control of pore size and shape, porosity, and interconnectivity of pores that contribute to structural stability. All mentioned properties can be upgraded or complemented with the specific properties of MNPs (e.g., biocompatibility and positive effect on cell proliferation). Considering the latest related literature and a steadily increasing number of related publications, the fabrication of magnetically responsive scaffolds is among the most interesting strategies in tissue engineering. According to the literature, incorporating MNPs into scaffolds can improve their mechanical properties and significantly affect biological properties, such as cellular responses. Moreover, under the influence of an external magnetic field, MNPs significantly promoted cell adhesion, proliferation, and differentiation