Abstract
To examine the effect of replacing the N-terminal amino group in opioid peptides with a methyl group on biological activity, a stereospecific synthesis of the tyrosine analogue (2S)-2-methyl-3-(2',6'-dimethyl-4'-hydroxyphenyl)-propionic acid (Mdp) was performed. The enkephalin analogue (2S)-Mdp-D-Ala-Gly-Phe-Leu-NH2 turned out to be a quite potent delta opioid antagonist and a somewhat less potent mu antagonist, indicating that a positively charged N-terminal amino group is not a conditio sine qua non for the binding of opioid peptides to delta and mu receptors but may be required for signal transduction.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brain
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Enkephalins / chemical synthesis
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Enkephalins / pharmacology
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Guinea Pigs
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Ileum / drug effects
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Inhibitory Concentration 50
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Male
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Membranes / chemistry
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Mice
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Muscle Contraction / drug effects
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Opioid Peptides / chemical synthesis*
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Opioid Peptides / metabolism
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Opioid Peptides / pharmacology
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Phenols
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Propionates / chemical synthesis
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Propionates / pharmacology*
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Protein Binding
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Rats
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Receptors, Opioid, delta / antagonists & inhibitors*
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, mu / antagonists & inhibitors
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Receptors, Opioid, mu / metabolism
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Stereoisomerism
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Structure-Activity Relationship
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Vas Deferens / drug effects
Substances
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2-methyl-3-(2',6'-dimethyl-4'-hydroxyphenyl)-propionic acid
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Enkephalins
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Opioid Peptides
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Phenols
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Propionates
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Receptors, Opioid, delta
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Receptors, Opioid, mu