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.
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