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首页> 外文会议>International Peptide Symposium;European Peptide Symposium >Identification of opioid receptor ligand interactions using structurally related delta-opioid receptor agonists and antagonists and molecular modeling.
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Identification of opioid receptor ligand interactions using structurally related delta-opioid receptor agonists and antagonists and molecular modeling.

机译：使用结构相关的δ-阿片类受体激动剂和拮抗剂和分子建模鉴定阿片受体配体的相互作用。

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Opioid receptors(delta,mu,kappa)and their endogenous ligands(enkephalins,endorphins,dynorphins,endomorphins)are located in the CNS and known for their efficacy in nociception.Plant derived and synthetic opioid compounds have served as effective therapeutics not only for treating pain,but also for immunosuppression,cocaine addiction,autism and Tourette's syndrome.These findings led to the development of compounds specifically targeted for opioid receptors as potential treatments for a number of human illnesses that span beyond pain control.Major challenges facing opioid ligand design include limited information regarding the mechanism of ligand-receptor association and the absence of bioactive conformations.Previously,we developed a hypothesis that describes the binding of agonist and antagonist opioid peptides containing the pharmacophores 2,6-dimethyltyrosine(Dmt),1,2,3,4-tetrahydroisoquinoline carboxylic acid(Tic)and lH-benzimidazole-2-yl(Bid)to the 8-opioid receptor.Conformers with agonist bioactivities displayed binding in two regions of the receptor:(a).Receptor residues R192,H301,H274,Y129 with Dmt and Bid in the aromatic pocket defined by F222,W274,Y308,F218,F270 and(b).Receptor residues D128,D95,N131,Y56,and Q105 with Dmt,Tic near W274,F270,F133 and Bid in the aromatic region.Low energy conformers of the antagonist derivatives displayed interactions in only one region of the receptor,similar to the first mechanism described for agonist analogues.
机译：阿片受体（Delta，Mu，Kappa）及其内源性配体（Enkephalins，内啡肽，羟基啉，胚乳）位于CNS中，并以其在伤害的效果中已知。衍生的和合成的阿片类化合物已经用作有效的治疗剂不仅用于治疗疼痛，但也用于免疫抑制，可卡因成瘾，自闭症和Tourette的综合征。这些结果导致了特异性靶向阿片受体的化合物作为许多人类疾病的潜在治疗，这些疾病超越了止痛调控。面临阿片类配体设计的Major挑战包括关于配体 - 受体结合机制和生物活性构象的情况有限的信息。因此，我们开发了一个假设，描述了含有药镜2,6-二甲基卵苷（DMT），1,2,3的激动剂和拮抗剂阿片类药物肽的结合。 ，4-四羟基喹啉羧酸（TIC）和LH-苯并咪唑-2-基（BID）至8-阿片受体。结合器激动剂生物活像在受体的两个区域中显示的结合：（a）。重复残留物R192，H301，H274，Y129，具有DMT和芳香袋中的ZID，由F222，W274，Y308，F218，F270和（B）定义。重点残留物D128，D95，N131，Y56和Q105与DMT，TIC近W274，F270，F133和芳族区域中的出价。拮抗剂衍生物的能量簇在受体的一个区域中显示相互作用，类似于所描述的第一机制对于激动剂类似物。

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