Design, preparation and biological evaluation of libraries of marocyclic delta opioid receptor agonists for the treatment of pain

点击翻译按钮获取中文摘要

The overall goal of this research proposal is to provide novel peptide-based DOPr (delta opioid receptor) agonists for the treatment of chronic pain. Although numerous peptide and non-peptide DOPr agonists have been developed over the past 30 years, very few compounds have reached clinical trials and, most importantly, nowadays none of them have been approved for clinical use. Originality and novelty of this research proposal relies on the fact that we will synthesize libraries of novel cyclic enkephalin analogs which will ultimately afford drug-like molecules with better stability, enhanced delivery and greater selectivity toward DOPr. As a matter of fact, we already have synthesized such macrolactams with improved affinity for DOPr and our industrial collaborator, Cyclenium Pharma, will help us preparing biased libraries of cyclic peptides structurally related to our already potent molecules. Furthermore, our computational analysis of structure-activity and structure-selectivity relationships and PET imaging approaches will assist us during the design of the libraries.