Highly-controlled and site-selective chemoenzymatic reactions
Most antibody-based PET imaging agents and antibody-drug conjugates (ADCs) are synthesised using non-selective bioconjugation methods. This involves attachment of the chelating agent or drug to amine- or carboxylic acid-containing amino acids which make up the antibody. As a result, the ‘product’ is actually a mixture of antibody-conjugates with different numbers of attachments to different sites on the antibody in a huge number of possible combinations. While most antibody-conjugates used in the clinic are made in this way, it is well-recognised that this is far from ideal because each compound in the mixture will have different pharmacological properties.
To address this, we are researching superior chemoenzymatic bioconjugation strategies which allow the highly controlled attachment of a fixed number of chemical groups (including: radiometal chelates, near-infrared fluorophores, drugs, click chemistry reagents, and so on) to well-defined sites on the antibody structure.
You can find out more about site-selective modifcation of antibodies here.
A chemoenzymatic method for the controlled and site-selective modification of antibodies