Sabatucci Annalaura, Tortolani Daniel, Dainese Enrico, Maccarrone Mauro
Faculty of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, Teramo, Italy.
Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
Biotechnol Appl Biochem. 2018 Jan;65(1):21-28. doi: 10.1002/bab.1589. Epub 2018 Jan 3.
The recent resolution of the crystal structure of type-1 cannabinoid receptor (CB ) and the discovery of novel modulators for this target open the way to the possibility of elucidating the structural requirements for CB binding, and thereby facilitate a rational drug design. Compounds that target the orthosteric site of CB in some cases have shown side effects. Allosteric modulators could potentially avoid these side effects by influencing binding and/or efficacy of orthosteric ligands. Here, we summarize and compare previous data on different putative allosteric binding sites observed in CB homology models with an in silico docking study of the recently published crystal structure of the same receptor on endogenous and natural hydrophobic ligands that act as positive allosteric modulators and negative allosteric modulators of CB . In particular, a lipid-exposed pocket targeted by most of the tested molecules is reported and discussed.
1型大麻素受体（CB）晶体结构的最新解析以及针对该靶点的新型调节剂的发现，为阐明CB结合的结构要求开辟了道路，从而有助于进行合理的药物设计。在某些情况下，靶向CB正构位点的化合物已显示出副作用。变构调节剂可能通过影响正构配体的结合和/或效力来避免这些副作用。在此，我们通过对同一受体最近发表的晶体结构进行计算机对接研究，总结并比较了在CB同源模型中观察到的不同假定变构结合位点的先前数据，该研究针对作为CB正变构调节剂和负变构调节剂的内源性和天然疏水性配体。特别是，报告并讨论了大多数测试分子所靶向的一个脂质暴露口袋。
