Tryptophan-Containing Non-Cationizable Opioid Peptides – a new chemotype with unusual structure and in vivo activity

摘要: Recently, a new family of opioid peptides containing tryptophan came to the spotlight for absence fundamental protonable tyramine 'message' pharmacophore. Structure-activity relationship investigations led diverse compounds, characterized by different selectivity profiles and agonist or antagonist effects. Substitution at indole Trp clearly impacted peripheral/central antinociceptivity. These peculiarities prompted gather all compounds in class, coin definition 'Tryptophan-Containing Non-Cationizable Opioid Peptides', short 'TryCoNCOPs'. Molecular docking analysis suggested that TryCoNCOPs can still interact with receptors an agonist-like fashion. However, most showed significant differences between vitro vivo activities, suggesting activity may be elicited also via alternative mechanisms.