20.500.12556/RUL-186230 Priprava hidrofilnih karboranskih reagentov za modifikacije malih molekul, peptidov in proteinov Preparation of hydrophilic carborane reagents for the modification of small molecules, peptides, and proteins V diplomskem delu smo sintetizirali nov tip hidrofilnih karboranskih NHS-estrskih reagentov, ki omogočajo modifikacije malih molekul, peptidov in proteinov za aplikacije pri terapiji z zajetjem nevtronov v boru (BNCT). Iz m-karboran-1,7-dikarboksilne kisline smo pripravili mono-NHS in bis-NHS ester ter reaktivnost obeh potrdili z reakcijo z modelnim aminom. Bis-NHS ester smo uspešno uporabili za intramolekularno ciklizacijo treh peptidov, pri enem smo z SPPS pristopom in ortogonalno zaščitenimi lizinskimi ostanki dosegli visoko stopnjo nadzora ciklizacije. Klinično uveljavljeno protitelo trastuzumab smo konjugirali z mono-NHS estrom, ki je v primerjavi z literaturnimi analogi funkcionaliziran z dodatno karboksilno skupino za izboljšano topnost v vodnih medijih. Pri uporabi 200 ekvivalentov reagenta smo dosegli razmerje učinkovina-protitelo (DAR) 5,8, kar nakazuje ugoden vpliv karboksilne kisline na kapaciteto konjugacije. Rezultati predstavljajo dobro izhodišče za nadaljnji razvoj hidrofilnih karboranskih konjugatov za uporabo v BNCT. Within this diploma thesis we synthesized new type of hydrophilic carborane NHS ester reagents that enable the modification of small molecules, peptides, and proteins for their potential use in boron neutron capture therapy (BNCT). Starting from m-carborane-1,7-dicarboxylic acid, we prepared both mono-NHS and bis-NHS ester and confirmed the reactivity of each through reaction with a model amine. The bis-NHS ester was successfully employed for the intramolecular cyclization of three peptides. For one peptide, solid phase peptide synthesis (SPPS) approach combined with orthogonally protected lysine residues enabled a high degree of control for cyclization process. Clinically established antibody trastuzumab was conjugated using novel mono-NHS ester, which was functionalized with a carboxylic group to improve aqueous solubility. Using 200 equivalents of the reagent, an antibody-to-drug ratio (DAR) of 5,8 was achieved, indicating a favourable effect of carboxylic acid group on conjugation capacity. The obtained results provide a solid foundation for further development of carborane conjugates for potential BNCT applications. karborani BNCT NHS ester biokonjugacija ciklični peptidi carboranes BNCT NHS ester bioconjugation cyclic peptides true false false Slovenski jezik Angleški jezik Diplomsko delo/naloga 2026-08-28 13:26:02 2026-08-28 13:26:02 2026-08-29 04:41:00 0000-00-00 00:00:00 2026 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 2027-08-27 25727 Jemc_Dane_-_Priprava_hidrofilnih_karboranskih_reagentov_za_modifikacije_malih_molekul,_peptidov_.pdf Jemc_Dane_-_Priprava_hidrofilnih_karboranskih_reagentov_za_modifikacije_malih_molekul,_peptidov_.pdf 1 ADE6C94D89CEA1690CFC18B707F14073 ca928bf253b8885eaf60194ed8fff96e08616b155dc0786fa452643bdd8e493e d451d5f5-a2d2-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=245356 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0