异源二聚体诱导：一种独特药理学的方法？
Heteromer Induction: An Approach to Unique Pharmacology?
机构信息
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota 55455, United States.
出版信息
ACS Chem Neurosci. 2017 Mar 15;8(3):426-428. doi: 10.1021/acschemneuro.7b00002. Epub 2017 Jan 31.
It is proposed that two types of opioid receptor heteromers exist: a) those that are constitutive and b) those that are induced by bivalent ligands. Mu opioid agonists interact with constitutive MOR-DOR heteromer to mediate tolerance and dependence. Bivalent ligand, MDAN21, is devoid of these adverse effects by virtue of its DOR antagonist pharmacophore. We propose that bivalent ligands MMG22 and MCC22 induce colocalized receptors to form heteromers (MOR-mGluR5 and MOR-CCR5, respectively) that do not occur naturally, thereby promoting unique pharmacology. Heteromer induction with bivalent ligands offers a general approach to unique pharmacology that complements traditional SAR.
据提议，存在两种类型的阿片受体异源二聚体：a）组成型的，和 b）由二价配体诱导的。μ 阿片受体激动剂与组成型 MOR-DOR 异源二聚体相互作用，介导耐受和依赖。二价配体 MDAN21 由于其 DOR 拮抗剂药效团而没有这些不良反应。我们提出，二价配体 MMG22 和 MCC22 诱导共定位受体形成异源二聚体（分别为 MOR-mGluR5 和 MOR-CCR5），这些异源二聚体不会自然发生，从而促进独特的药理学。用二价配体诱导异源二聚体为独特的药理学提供了一种通用方法，补充了传统的 SAR。
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