20.500.12556/RUL-169832 Sinteza naftalenskih derivatov in njihova vezava na vmesnika The synthesis of fluorescent naphthalene derivates and their binding to the selected linkers Alzheimerjeva bolezen je najpogostejša nevrodegenerativna bolezen in oblika demence, za katero je značilno kopičenje depozitov amiloida β in prekomerno fosforiliranih proteinov tau. Te biooznačevalce Alzheimerjeve bolezni je mogoče detektirati z uporabo majhnih molekulskih sond in primernih eksperimentalnih tehnik. Cilj magistrske naloge je bila preliminarna študija, kjer bi ugotovili, ali je vezavno afiniteto izbrane molekulske sonde na omenjene biooznačevalce možno izboljšati na način, da jih po dve (v nadaljevanju imenovani monomeri) s pomočjo ustreznega povezovalnega elementa združimo v t.i. dimere. Najprej smo sintetizirali prosto molekulsko sondo oz. monomerno enoto, 1-(6-((2-hidroksietil)(metil)amino)naftalen-2-il)ethan-1-on. 2-Hidroksietilno skupino v slednji smo nato uporabili za vezavo na dikarboksilni povezovalni element, pripravljen z monoestrenjem med N-Boc zaščitenim 7-azatetraetilenglikolom in dvema anhidridoma jantarne kisline. Tako smo dobili N-Boc zaščiten dimer, kateremu smo odstranili Boc zaščito in mu izmerili vezavno afiniteto do fibrilov Aβ$_{1–42}$. Ta je bila približno dvakrat večja od tiste za monomer (prosto molekulsko sondo). Alzheimer's disease is the most common neurodegenerative disease and the most prevalent form of dementia, characterized by the accumulation of amyloid β deposits and hyperphosphorylated tau proteins. These biomarkers of Alzheimer's disease can be detected using small molecule probes in combination with suitable experimental techniques. The aim of this work was a preliminary study to investigate whether the binding affinity of the selected molecular probe to the aforementioned biomarkers can be enhanced by linking the two probe units (referred to as monomers) through a suitable linker to form so-called dimers. Initially, we synthesized a free molecular probe, the monomer unit, 1-(6-((2-hydroxyethyl)(methyl)amino)naphthalen-2-yl)ethan-1-one. The 2-hydroxyethyl group in this compound was then used to couple it to a dicarboxylic linker, which was synthesized via monoesterification of N-Boc protected 7-azatetraethylene glycol with two molar equivalents of succinic anhydride. This yielded an N-Boc protected dimer, which was subsequently deprotected and its binding affinity to Aβ$_{1–42}$ fibrils was measured. The results demonstrated that the dimer exhibited approximately twice the binding affinity compared to the monomeric probe. sinteza molekulska sonda etilenglikol jantarna kislina estrenje synthesis molecular probe ethylene glycol succinic acid esterification true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2025-06-12 09:45:02 2025-06-12 09:45:13 2025-06-13 11:25:51 0000-00-00 00:00:00 2025 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 25375 239270659 Klander_Dasa_-_Sinteza_fluorescentnih_naftalenskih_derivatov_in_njihova_vezava_na_izbrana_vmesni.pdf Klander_Dasa_-_Sinteza_fluorescentnih_naftalenskih_derivatov_in_njihova_vezava_na_izbrana_vmesni.pdf 1 C9C7D997B1A025BF38E4D21AB8987623 cd8053582fed94c3f6b66928f678807f9b0caf165dbf7c97fb90bd4b4b6aba61 aeda415b-475f-11f0-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=211544 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0