20.500.12556/RUL-169372 Razvoj sinteznih metod za vgradnjo nenaravnih fragmentov v polipeptidne verige Development of synthetic methods for the incorporation of non-natural fragments into polypeptide chains V okviru magistrskega dela smo se ukvarjali z razvojem metod za vgradnjo nenaravnih fragmentov, natančneje spojin razreda dikarba-closo-dodekaboranov (karboranov), v polipeptidne verige in s sintezo peptidov. Izbira karboranov temelji na njihovi potencialni uporabi v medicini, kjer lahko posnemajo karbociklična ogrodja in so zaradi visoke vsebnosti bora zanimivi za BNCT (angl. Boron Neutron Capture Therapy). Vgradnja karboranov v polipeptide je potekala na različne načine, poglaviten med njimi je temeljil na pripravi N-hidroksisukcinimid (NHS) estrov in reakcije teh z ε-aminsko skupino stranske verige aminokisline lizina (Lys). Pripravili smo dva različna NHS reagenta, ki vsebujeta karboransko zvrst in ju testirali v reakcijah biokonjugacij na modelnih peptidih, ki smo jih pripravili sami. Vgradnjo karboranov smo izvedli tudi preko aktivirane 1,7-dikarba-closo-dodekaboran-1-karboksilne kisline s sledečim spajanjem s peptidno verigo, in tudi preko priprave nenaravne aminokisline, ki je vsebovala karboransko skupino in smo jo v polipeptidno verigo uvedli z uporabo avtomatizirane SPPS (angl. Solid-phase peptide synthesis). Sočasno smo se ukvarjali z razvojem komplementarne sinteze metode za pripravo peptidov in sicer preko optimizacije priprave krajših polipeptidov z uporabo zelenih topil, nezaščitenih aminokislin in cenejših aktivatorjev. Within this thesis, we were developing methods for incorporation of unnatural fragments, specifically compounds of the dicarba-closo-dodecaborane class (carboranes), into polypeptide chains and synthesizing peptides. The selection of carboranes was based on their potential use in medicine, where they can mimic carbocyclic frameworks and are of interest for BNCT (Boron Neutron Capture Therapy) due to their high boron content. The incorporation of carboranes into peptides was carried out in various ways. The most important among them was based on the preparation of N-hydroxysuccinimide (NHS) esters and their reaction with the ε-amino group of the lysine side chain. We prepared two different NHS reagents containing the carborane group and tested bioconjugation reactions on model peptides, which we prepared in advance. The incorporation of carboranes into peptides was also achieved via activated dicarba-closo-dodecaborane carboxylic acid with subsequent coupling, and by the preparation of a carborane-functionalized amino acid, which was introduced into the peptide using automated SPPS. In paralel, we worked on development of method for peptide synthesis through preparation of shorter polypeptides using green solvents, unprotected amino acids, and more cost-effective activators. dikarba-closo-dodekaboran BNCT polipeptidi N-hidroksisukcinimid ester biokonjugacija. dicarba-closo-dodecaboran BNCT polypeptide N-hydroxysuccinimide ester bioconjugation. true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2025-05-26 10:30:02 2025-05-26 10:30:11 2025-05-29 12:44:28 0000-00-00 00:00:00 2025 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 2026-05-26 24253 237658371 Barbic_Urban_-_Razvoj_sinteznih_metod_za_vgradnjo_nenaravnih_fragmentov_v_polipeptidne_verige.pdf Barbic_Urban_-_Razvoj_sinteznih_metod_za_vgradnjo_nenaravnih_fragmentov_v_polipeptidne_verige.pdf 1 079E9ACBB29FEAC3B968BFAEED3B6336 8eadad3c71ae2c80c8844d7d758f08b00415067a8be4f9fbd08fd39e12009493 5a12b096-3a0a-11f0-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=210677 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0