A paper regarding a new unnatural amino acid on modified lysine and its synthesis and application was recently published in “Bioconjugate Chemistry”.

The paper reports a new lysine amino acid capable of efficient incorporation into antibodies and subsequent coupling with maleimide via a Diels-Alder reaction. This new lysine was stable throughout protein expression in mammalian cells and enabled covalent attachment of maleimide drug-linkers yielding Diels-Alder antibody-drug conjugates (DA-ADCs) with nearly quantitative conversion in a one-step process.

The Diels-Alder bioconjugation strategy represents a simple method to produce site-specific and stable ADCs with maleimide drug-inkers.

 SynChem chemists are actively involved in this project.
This paper can be found at DOI: 10.1021/acs.bioconjchem.9b00436.