The fine tuning of high affinity and selective non-peptide agonists of the δ-opioid receptor via solution and solid-phase

Peptide Science: Exploring the Use of Chemical Principles and Interdisciplinary Collaboration for Understanding Life Processes

“…Thus, we are continuing to develop synthetic strategies that will lead to nontoxic peptidomimetics in related structural classes. 75,76 As discussed above, we have hypothesized that "simple" changes in topography of key pharmacophore elements in peptide hormones and neurotransmitters can profoundly affect their bioactivities without any significant changes in backbone conformation. To examine further this hypothesis, we designed a highly constrained bicyclic oxytocin antagonist analogue in χ space 77 based on our previously designed bicyclic oxytocin analogue D-Pen-Tyr-Ile-Glu-Asn-Cys-Pro-Lys-Gly-NH 2 , which was a potent, prolonged acting oxytocin antagonist at the uterine oxytocin receptor.…”

“…However, these de novo designed non-peptide mimetics show significant toxicity, much like other non-peptide opioids. Thus, we are continuing to develop synthetic strategies that will lead to nontoxic peptidomimetics in related structural classes. , …”