Rational design, synthesis and characterization of vitamin B12 bioconjugates as diagnostic and therapeutic drugs

The tumour cells take up proportionally more vitamin B12 than non-proliferating cells due to an increased number of surface receptors required for the endocytosis of the vitamin. Therefore, vitamin B12 derivatives have the potential application as diagnostic or therapeutic antitumour agents. The rational design of bioconjugates based on cyanocobalamin (vitamin B12) has been performed by exploiting the structural knowlegde about the complex of cobalamin with its human transport proteins that became recently available. The structures point to the 5’-hydroxyl group of the ribose moiety as the most promising site for the covalent attachment of active ligands to cobalamin to preserve the affinity of the resulting analogue for the transport proteins. The esterification of the ribosyl 5'-OH group of vitamin B12 with diethylenetriaminepentaacetic acid (DTPA) produces a chimeric molecule (B12-DTPA) able to chelate different metals. The gadolinium complex of this bioconjugate (B12-DTPA-Gd) has been characterized both in solution and in solid state.