Synthesis of Gly-ψ[(Z)CF═CH]-Phe, a Fluoroalkene Dipeptide Isostere, and Its Incorporation into a Leu-enkephalin Peptidomimetic
| Autor: | Guillaume Langlois, Louis Gendron, Sébastien Grastilleur, Thi Thanh Hà Dao, Brigitte Guérin, Véronique Blais, Kristina Rochon, Yves L. Dory, Jean-François Nadon |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Hydrocarbons Fluorinated Physiology Isostere Stereochemistry Peptidomimetic Cognitive Neuroscience Green Fluorescent Proteins Transfection 010402 general chemistry Binding Competitive 01 natural sciences Biochemistry Mice chemistry.chemical_compound Vas Deferens Cell Line Tumor Receptors Opioid delta Amide Animals Humans Peptide bond Phosphorylation Cell Line Transformed chemistry.chemical_classification Dipeptide 010405 organic chemistry Chemistry Hydrogen bond Dipeptides Cell Biology General Medicine Leu-enkephalin Rats 0104 chemical sciences Sulfonamide Peptidomimetics Enkephalin Leucine |
| Zdroj: | ACS Chemical Neuroscience. 8:40-49 |
| ISSN: | 1948-7193 |
| Popis: | A new Leu-enkephalin peptidomimetic designed to explore the hydrogen bond acceptor ability of the third peptide bond has been prepared and studied. This new analog is produced by replacing the third amide of Leu-enkephalin with a fluoroalkene. An efficient and innovative synthesis of the corresponding dipeptide surrogate Fmoc-Gly-ψ[(Z)CF═CH]-Phe-OH is described. The key step involves the alkylation of a tin dienolate from the less hindered face of its chiral sulfonamide auxiliary derived from camphor. Once its synthesis was complete, its incorporation into the peptidomimetic sequence was achieved on a solid support with chlorotrityl resin following the Fmoc strategy. The peptidomimetic was characterized using competition binding with [125I]-deltorphin I on membrane extracts of HEK293 cells expressing the mouse delta opioid receptor (DOPr) and based on its abilities to inhibit the electrically induced contractions of the mouse vas deferens and to activate the ERK1/2 signaling pathway in DRGF11/DOPr-GFP cel... |
| Databáze: | OpenAIRE |
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