Novel bio-conjugation agents for the modification of protein based therapeutics Seminar

Novel bio-conjugation agents for the modification of protein based therapeutics

Dr Andrew G. Watts, Department of Pharmacy and Pharmacology, University of Bath

The therapeutic use of peptide and protein based drugs, for instance insulin and growth hormone, has a history of several decades. However, the potentially huge impact of this class of drugs in therapy has become apparent only relatively recently as a result of advances in genomics and proteomics. These have led to the discovery of numerous protein and peptide drugs of therapeutic potential, with the protein engineering market being worth about $118 billion in 2011, or 12% of total pharma sales.
Effective use of peptide and protein drugs in the patient can, however, be compromised by their instability in the body, rapid rates of clearance, premature uptake by tissues, loss through the kidneys and immunogenicity. Concerted efforts have been made over the years to circumvent such problems, with one particular solution being to chemically modify the protein with molecules such as polyethylene glycol (PEG). However, the chemistries currently used for such protein modifications (pegylation) are not ideal and issues can include a lack of specificity and lack of stability of the conjugate at certain pH.
This talk will discuss our work towards developing alternative reagents for the chemical modification of protein based therapeutics, firstly looking to address issues such as specificity and stability, but also looking to identify methods that can expand the repertoire of protein conjugates – such as bi-specifics. We will also look at alternative ‘payloads’ to the traditional polyethylene glycol, and introduce the development of degradation resistant glycoproteins.