IRCM Researchers

1. Study of structure – activity relationships of biologically active peptides, using an interdisciplinary research approach based on chemical, pharmacological and biophysical techniques.

2. Medicinal chemistry and molecular pharmacology  of peptide hormones and  neuro-transmitters:

• Synthesis of novel amino acids
• Chemical synthesis (classical and solid-phase) of peptide  hormones and  neuro-
• transmitters and of  analogs containing natural  or artificial amino acids
• Study  of  conformational  aspects  of  peptide – receptor  interactions  by  NMR spectroscopy, fluorescence spectroscopy and computational molecular modeling
• Development of conformationally restricted peptide analogs and of peptidomimetics
• Receptor binding assays
• Bioassays in vitro and in vivo
• Development of peptide-based pharmacolgical tools and potential drugs

3. Major projects on opioid peptides:

• Design of agonists, antagonists and inverse agonists with high specificity for  the three opioid receptor types (μ, δ and κ)
• Development of mixed μ agonist/δ antagonists as analgesics with low propensity to produce tolerance and dependence
• Development of novel opioid-peptide derived compounds as centrally or peripherally acting analgesic drugs with reduced side effects
• Development of the first bifunctional compounds with mixed µ opioid agonist/antioxidant activity that are superior to morphine as analgesics for treatment of neuropathic pain
• These efforts resulted in compounds that are widely used as pharmacological tools (many of them distributed to the research community by the U.S. National Institutes of Health (NIH) Drug Supply System) or are being pursued as analgesic drug candidates

4. Development of mitochondria-protecting peptides

The so-called Szeto-Schiller (SS)-peptides,  co-designed  by P.W.  Schiller  and H.H. Szeto(Cornell Medical College) and  first  synthesized in our laboratory, are cell-penetrating and act at the inner mitochondrial membrane to protect mitochondrial function. They promote efficiency of electron transfer, enhance ATP synthesis, reduce electron leak and free radical production, and some of them also quench excessively generated reactive oxygen species (ROS). They hold great therapeutic potential for the treatment of various diseases associated with mitochondrial dysfunction, including primary mitochondrial diseases, diseases associated with aging and neurodegenerative diseases. The IRCM and the Cornell Research Foundation hold several joint patents on SS-peptides and their clinical development is pursued by the start-up  company  Stealth BioTherapeutics, Inc. Stealth went public in March 2018 and their shares are now traded on the Nasdaq Global Market. Phase 2 and 3 clinical trials with the lead compound “elamipretide” (SS-31)  for various indications of both common and  rare  mitochondrial  diseases (age-related macular degeneration, Barth syndrome, Leber’s hereditary optic neuropathy) are ongoing.