Antibody drug conjugates (ADCs) are one of the most promising technologies to treat
cancer as they combine the specificity of an antibody with the high potency of a cytotoxic molecule such as
tomaymycin derivatives, which are
DNA-interactive antitumor
antibiotics previously isolated from bacterial broth. The multistep chemical synthesis of some
tomaymycin derivatives is complicated because their structures contain a reactive
imine bond. Therefore, we turned to biosynthesis to obtain 14 C radiolabelled
tomaymycin derivative to support ADME studies. Following Hurley's work (J.
Antibiotics 1977, 30, 349-370; Antimicrob. Agents Chemother. 1979, 15, 42-45; Acc. Chem. Res. 1980, 13, 263-269), the 14 C radiolabel was incorporated efficiently in one step from radiolabelled
tyrosine using the strain Streptomyces sp. FH6421. This process has been further optimized by using
anthranilic acid as radiolabelled precursor, leading to one of the highest incorporation levels of radiochemical precursors published to date. This biosynthetic strategy is the fastest way to access such radiolabelled precursors.