Targeting Receptor Complexes with Therapeutic Peptides
Kristian Stromgaard
Professor, University of Copenhagen
Protein-protein interactions (PPIs) are essential to vital cellular processes, and serve as potential targets for therapeutic intervention. We are particularly interested in the PPIs between integral membrane protein receptors and their intracellular protein partners, so-called ‘receptor complexes’ and examine how modulation of such receptor complexes PPIs can provide novel biological insight and new therapeutics. We have developed peptide-based inhibitors of the PSD-95/glutamate receptor interaction, as potential treatment for acute conditions such as acute ischemic stroke. Specifically, we have exploited that PSD-95 contains a tandem PDZ1-2 domain and have designed and synthesized dimeric peptides with low nanomolar affinities, and have demonstrated that these ligands are potential treatment for ischemic stroke. The lead compound AVLX-144 was recently successfully examined in a Phase I clinical trials. Similarly, we have developed potential therapeutic peptides for a number of PPIs in other therapeutically relevant receptor complexes.
Kristian Strømgaard is professor at University of Copenhagen and co-founder and CEO of Avilex Pharma. He obtained an MSc degree in Chemical Research from University College London, and continued as a PhD student in medicinal chemistry, part-time at the Danish pharmaceutical company H. Lundbeck. He did a postdoc at Columbia University (New York), and was then appointed H. Lundbeck Professor at the age of 36 to establish research in Chemical Biology. He won the ‘Teacher of the Year’ award from the Faculty of Pharmaceutical Science (UCPH) in 2009. In 2012, he co-founded Avilex Pharma and has taken the lead compound into clinical development. In 2014, he was appointed Director of Center for Biopharmaceuticals. Recently, he was visiting professor at Harvard Medical School.