Přednáška: Rajesh Khanna
Discovery and characterization of bioinspired, peptidomimetic, and computationally-identified small molecule analgesics for chronic pain
The use of natural products has increased in the last three decades with no less than 80% of people worldwide relying on them for some part of primary healthcare but, despite their escalating use, many remain untested due to a lack of understanding of their targets and modes of action. The Khanna laboratory aims to validate the targets of action of analgesic natural products and characterize their mode of action. We also utilize pharmacophore modelling to generate small molecule peptidomimetics to improve upon the biological activity of analgesic peptides by mimicking the chemical features responsible for bioactivity with enhanced drug-like properties. In this vein, we have developed a molecular dynamics simulation-based pipeline to identify residues in peptides important for initial complex formation (anchor residues) for pharmacophore modeling. Dr. Khanna will illustrate how his laboratory used this motif for a pharmacophore screen to identify first-in-class small molecule peptidomimetics to disrupt the interaction of a clinically validated analgesic protein. The understanding gained from these studies has the potential to lead to fast-tracking development of novel, non-addictive drugs for treatment of chronic neuropathic pain and associated comorbid conditions in humans.