Toward a Universal μ-Agonist Template for Template-Based Alignment Modeling of Opioid Ligands
AffiliationUniv Arizona, Dept Chem & Biochem
MetadataShow full item record
PublisherAMER CHEMICAL SOC
CitationACS Omega 2019, 4, 17457−17476
RightsCopyright © 2019 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
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AbstractOpioid ligands are a large group of G-protein-coupled receptor ligands possessing high structural diversity, along with complicated structure–activity relationships (SARs). To better understand their structural correlations as well as the related SARs, we developed the innovative template-based alignment modeling in our recent studies on a variety of opioid ligands. As previously reported, this approach showed promise but also with limitations, which was mainly attributed to the small size of morphine as a template. With this study, we set out to construct an artificial μ-agonist template to overcome this limitation. The newly constructed template contained a largely extended scaffold, along with a few special μ-features relevant to the μ-selectivity of opioid ligands. As demonstrated in this paper, the new template showed significantly improved efficacy in facilitating the alignment modeling of a wide variety of opioid ligands. This report comprises of two main parts. Part 1 discusses the general construction process and the structural features as well as a few typical examples of the template applications and Part 2 focuses on the template refinement and validation.
NoteOpen access journal
VersionFinal published version
- A constitutively internalizing and recycling mutant of the mu-opioid receptor.
- Authors: Segredo V, Burford NT, Lameh J, Sadée W
- Issue date: 1997 Jun
- 3D modeling, ligand binding and activation studies of the cloned mouse delta, mu; and kappa opioid receptors.
- Authors: Filizola M, Laakkonen L, Loew GH
- Issue date: 1999 Nov
- Backbone alignment modeling of the structure-activity relationships of opioid ligands.
- Authors: Wu Z, Hruby VJ
- Issue date: 2011 May 23
- A chimeric analysis of the opioid receptor domains critical for the binding selectivity of mu opioid ligands.
- Authors: Watson B, Meng F, Akil H
- Issue date: 1996 Feb
- Synthesis, opioid receptor binding, and bioassay of naltrindole analogues substituted in the indolic benzene moiety.
- Authors: Ananthan S, Johnson CA, Carter RL, Clayton SD, Rice KC, Xu H, Davis P, Porreca F, Rothman RB
- Issue date: 1998 Jul 16