χ-Space Screening of Dermorphin-Based Tetrapeptides through Use of Constrained Arylazepinone and Quinolinone Scaffolds
| العنوان: | χ-Space Screening of Dermorphin-Based Tetrapeptides through Use of Constrained Arylazepinone and Quinolinone Scaffolds |
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| المؤلفون: | Louis Gendron, Dirk Tourwé, Frédéric Bihel, Nga N. Chung, Peter W. Schiller, Olivier Van der Poorten, Cecilia Betti, Robin Van Den Hauwe, Karel Guillemyn, Emilie Eiselt, Steven Ballet, François Hallé, Philippe Sarret |
| المساهمون: | Laboratoire d'Innovation Thérapeutique (LIT), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Department of Organic Chemistry, Vrije Universiteit Brussel (VUB), Department of Physiology and Biophysics, Université de Sherbrooke (UdeS), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC) |
| المصدر: | ACS Medicinal Chemistry Letters ACS Medicinal Chemistry Letters, American Chemical Society, 2017, 8 (11), pp.1177-1182. ⟨10.1021/acsmedchemlett.7b00347⟩ |
| بيانات النشر: | HAL CCSD, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, chemistry.chemical_classification, Tetrapeptide, 010405 organic chemistry, Stereochemistry, Organic Chemistry, Peptide, Dermorphin, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 01 natural sciences, Biochemistry, Combinatorial chemistry, ANT, 0104 chemical sciences, Amino acid, 03 medical and health sciences, chemistry.chemical_compound, Residue (chemistry), 030104 developmental biology, chemistry, Drug Discovery, Receptor, Selectivity, ComputingMilieux_MISCELLANEOUS |
| الوصف: | Herein, the synthesis of novel conformationally constrained amino acids, 4-amino-8-bromo-2-benzazepin-3-one (8-Br-Aba), 3-amino-3,4-dihydroquinolin-2-one, and regioisomeric 4-amino-naphthoazepinones (1- and 2-Ana), is described. Introduction of these constricted scaffolds into the N-terminal tetrapeptide of dermorphin (i.e., H-Tyr-d-Ala-Phe-Gly-NH2) induced significant shifts in binding affinity, selectivity, and in vitro activity at the μ- and δ-opioid receptors (MOP and DOP, respectively). A reported constrained μ-/δ-opioid lead tetrapeptide H-Dmt-d-Arg-Aba-Gly-NH2 was modified through application of various constrained building blocks to identify optimal spatial orientations in view of activity at the opioid receptors. Interestingly, when the aromatic moieties were turned toward the C-terminus of the peptide sequences, (partial) (ant)agonism at MOP and weak (ant)agonism at DOP were noticed, whereas the incorporation of the 1-Ana residue led toward balanced low nanomolar MOP/DOP binding and in vitro ago... |
| اللغة: | English |
| تدمد: | 1948-5875 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0eb26d3a07e8388d155d1e134bca1b18 https://hal.archives-ouvertes.fr/hal-02368778 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0eb26d3a07e8388d155d1e134bca1b18 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 19485875 |
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