Antibody-Drug Conjugates
We develop methods for the site-selective modification of antibodies. To do this efficiently, we convert the proteinogenic amino acid tyrosine into its corresponding ortho-quinone using tyrosinase. This product rapidly reacts with the strained alkene cpTCO (3000 1/M•s) or alkyne BCN (1000 1/M•s). We can perform this modification on the C- or N-terminus of both the LC and HC of antibodies, but also in exposed internally positioned Tyr residues. Even though the workhorse-antibody for this project is trastuzumab, we have not yet seen modification of Tyr57 that is positioned in the CDR of the antibody. Therefore, we have a highly selective method to prepare ADCs that does not interfere with antigen binding. One of our latest published work describes the rapid and efficient dual labeling of the antibody trastuzumab with MMAE and lissamine, leading to a site-selectively modified antibody-drug-dye conjugate (paper #44). Even more recent is the application of knob-in-hole antibodies to generate mono-functionalized antibody-protein conjugates (paper #52). Yet unpublished work will reveal how we can do this on non-engineered antibodies, so stay tuned!
Peptide Chemistry
We recently started an ambitious project where we will prepare peptide-based plant hormones that are able to boost the regeneration of plants. In this project, we also want to develop robust methods for green peptide synthesis by rethinking amide-bond formation. Using our expertise on classical solid-phase peptide synthesis methods, we prepared peptides that contained fluorescent rotors to monitor the microviscosity of living plant cells (paper #55). Lastly, we are also involved in a Citizen Science project where we immobilize peptides on surfaces for the targeted interaction with spores.
New Click and Un-Click Chemistry
Clicking large biomolecules to each other is an important strategy in the preparation of biomolecules that displayed tailored biological activities. The revers approach is also valuable, as un-clicking of a conjugated potent entity can result in the local delivery of this, potentially more potent, entity. We're developing two novel methods to do this, one based on organic molecules, the other based on a metal complex.
