Structure-activity relationships of bifunctional cyclic disulfide peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors
| Autor: | Richard S. Agnes, Yeon Sun Lee, Josephine Lai, Victor J. Hruby, Katalin E. Kövér, Hamid Badghisi, Peg Davis, Shou Wu Ma, Jinfa Ying, Frank Porreca |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Agonist medicine.medical_specialty Physiology medicine.drug_class Narcotic Antagonists Molecular Sequence Data Peptides Cyclic digestive system Biochemistry Cholecystokinin receptor Article Structure-Activity Relationship Cellular and Molecular Neuroscience chemistry.chemical_compound Endocrinology Természettudományok Internal medicine medicine Amino Acid Sequence Disulfides Opioid peptide Kémiai tudományok G protein-coupled receptor Cholecystokinin digestive oral and skin physiology DAMGO chemistry Opioid Drug Design Receptors Opioid Receptors Cholecystokinin μ-opioid receptor hormones hormone substitutes and hormone antagonists medicine.drug |
| Popis: | Prolonged opioid exposure increases the expression of cholecystokinin (CCK) and its receptors in the central nervous system, where CCK may attenuate the antinociceptive effects of opioids. The complex interactions between opioid and CCK may play a role in the development of opioid tolerance. We designed and synthesized cyclic disulfide peptides and determined their agonist properties at opioid receptors and antagonist properties at CCK receptors. Compound 1 (Tyr-c[D-Cys-Gly-Trp-Cys]-Asp-Phe-NH2) showed potent binding and agonist activities at δ and µ opioid receptors while displaying some binding to CCK receptors. The NMR structure of the lead compound displayed similar conformational features of opioid and CCK ligands. |
| Databáze: | OpenAIRE |
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