An amino acid-based heterofunctional cross-linking reagent

We describe the synthesis and characterization of a new lysine-based heterofunctional cross-linking reagent. It carries two readily available aminooxy functionalities and an activated and protected thiol group that is capable of generating reducible disulfides, the former enable bioorthogonal modification of ketones and aldehydes by the formation of an oxime bond. The efficacy of the linker was proven by coupling two doxorubicin molecules to the functionalized amino acid core and the subsequent bioconjugation of this drug conjugate with a thiolated antibody.