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Journal Article
Research Support, Non-U.S. Gov't
Review
Tryptophan-Containing Non-Cationizable Opioid Peptides - a new chemotype with unusual structure and in vivo activity.
Future Medicinal Chemistry 2017 November
Recently, a new family of opioid peptides containing tryptophan came to the spotlight for the absence of the fundamental protonable tyramine 'message' pharmacophore. Structure-activity relationship investigations led to diverse compounds, characterized by different selectivity profiles and agonist or antagonist effects. Substitution at the indole of Trp clearly impacted peripheral/central antinociceptivity. These peculiarities prompted to gather all the compounds in a new class, and to coin the definition 'Tryptophan-Containing Non-Cationizable Opioid Peptides', in short 'TryCoNCOPs'. Molecular docking analysis suggested that the TryCoNCOPs can still interact with the receptors in an agonist-like fashion. However, most TryCoNCOPs showed significant differences between the in vitro and in vivo activities, suggesting that opioid activity may be elicited also via alternative mechanisms.
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