Modification of amphipathic non-opioid dynorphin A analogues for rat brain bradykinin receptors
| Autor: | Ann Nguyen, Michael Remesic, Frank Porreca, Victor J. Hruby, David Rankin, Cyf Ramos-Colon, Lindsay LeBaron, Yeon Sun Lee, Sara M. Hall, Josephine Lai |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Clinical Biochemistry Central nervous system Pharmaceutical Science Bradykinin Dynorphin Pharmacology Dynorphins Biochemistry Article Structure-Activity Relationship chemistry.chemical_compound Internal medicine Drug Discovery medicine Animals Molecular Biology Chemistry Receptors Bradykinin fungi Organic Chemistry Antagonist Brain Dynorphin A respiratory system Rats Endocrinology medicine.anatomical_structure Opioid Hyperalgesia Molecular Medicine medicine.symptom Pharmacophore circulatory and respiratory physiology medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 25:30-33 |
| ISSN: | 0960-894X |
| Popis: | It has been shown that under chronic pain or nerve injury conditions, up-regulated dynorphin A (Dyn A) interacts with bradykinin receptors (BRs) to cause hyperalgesia in the spinal cord. Thus BRs antagonist can modulate hyperalgesia by blocking Dyn A’s interaction with the BRs in the central nervous system. In our earlier structure–activity relationship (SAR) study, [des-Arg 7 ]-Dyn A-(4–11) 13 was discovered as a minimum pharmacophore for rat brain BRs with its antagonist activity (anti-hyperalgesic effect) in in vivo tests using naive or injured animals. We have pursued further modification on the [des-Arg 7 ]-Dyn A analogues and identified a key insight into the pharmacophore of the rat brain BRs: amphipathicity. |
| Databáze: | OpenAIRE |
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