De Marco Rossella, Gentilucci Luca
Department of Chemistry "G Ciamician", University of Bologna, via Selmi 2, 40126-Bologna, Italy.
Future Med Chem. 2017 Nov;9(17):2099-2115. doi: 10.4155/fmc-2017-0104. Epub 2017 Nov 13.
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.
最近，一类新的含色氨酸的阿片肽因缺乏基本的可质子化酪胺“信息”药效团而备受关注。构效关系研究产生了多种化合物，其特点是具有不同的选择性特征以及激动剂或拮抗剂作用。色氨酸吲哚环上的取代明显影响外周/中枢抗伤害感受性。这些特性促使人们将所有这些化合物归为一个新类别，并创造了“含色氨酸的不可阳离子化阿片肽”这一定义，简称为“TryCoNCOPs”。分子对接分析表明，TryCoNCOPs仍能以类似激动剂的方式与受体相互作用。然而，大多数TryCoNCOPs在体外和体内活性之间存在显著差异，这表明阿片类活性也可能通过其他机制引发。
