PROGRAMME
Francesca Vianello (Yaliraki Lab): “Atomistic prediction of allosteric pathways across GPCR complexes”
Theo Flack (Barnard Lab): “Peptidomimetic inhibitors of a fully buried protein-helix interaction in the malaria motor complex”
Dr Jamie Baker (UCL): “Chemical reactions on antibodies; towards site-selective antibody conjugates as targeted therapeutics”
Abstract; Antibody drug conjugates (ADCs) represent one of the most exciting classes of new targeted therapies for cancer, and potentially other diseases. They combine the finely tuned targeting properties of antibodies with the potency of action of attached small molecule drugs. However, the chemistry used to construct such bioconjugates has been far from optimal in the first generation of ADCs which have made it to the clinic. In this seminar the limitations of these approaches will be discussed, and the requirements for optimal conjugation strategies laid out. Our investigations towards developing new reagents and protocols to allow the attachment of drugs to specific sites of the antibody, making use of disulfide bonds or inserted cysteine residues as reactive handles, will be described. Insights will also be given on the challenges of doing controlled chemistry on large biomolecules (and the associated analysis), the scope of attachments possible (e.g. attaching multiple proteins and drugs in a defined manner) and the future prospects in the field.
Bio; Dr Jamie Baker has been a Reader in Chemical Biology at UCL since Oct 2017. He previously held posts at UCL as a Senior Lecturer (2014-2017), Lecturer (2012-2014), and as an RCUK Research Fellow (2007-2012). His research interests are in the development and application of novel methodologies in bioconjugation, targeted therapeutics, and organic synthesis resulting in >35 peer reviewed articles, 2 granted patents and 3 further patent applications in these areas. He is also a co-founder of the spin-out company ThioLogics (www.thiologics.com), which commercialises site-specific conjugation methods for the assembly of next generation Biologics.