Abstract
Partially modified retro-inverso, retro, and inverso isomers of hydrazide linked bifunctional peptides were designed, synthesized, and evaluated for bioactivities at delta/mu opioid receptors and CCK-1/CCK-2 receptors. All modifications of the CCK pharmacophore moiety affected bioactivities for the CCK-1 and CCK-2 receptors (up to 180-fold increase in the binding affinity with higher selectivity) and for the delta and mu opioid receptors. The results indicate that the opioid and CCK pharmacophores in one molecule interact with each other to induce topographical changes for both pharmacophores.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Cell Line
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Cricetinae
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Cricetulus
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Humans
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Isomerism
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Molecular Structure
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / pharmacology
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Radioligand Assay
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Receptor, Cholecystokinin A / antagonists & inhibitors
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Receptor, Cholecystokinin B / antagonists & inhibitors
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Receptors, Cholecystokinin / antagonists & inhibitors*
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Receptors, Opioid / agonists*
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, mu / agonists
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Structure-Activity Relationship
Substances
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Oligopeptides
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Receptor, Cholecystokinin A
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Receptor, Cholecystokinin B
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Receptors, Cholecystokinin
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Receptors, Opioid
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Receptors, Opioid, delta
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Receptors, Opioid, mu