Abstract
The dopamine transporter plays an important role in the molecular mechanism of cocaine dependence. It is suggested that inhibitors of the dopamine transporter would have strong therapeutic potential. Here we report that aromatic modification can constrain a linear peptide into the beta-turn conformation, which is preferred by the dopamine transporter. On the basis of this finding, a novel selective and competitive peptidic inhibitor of the dopamine transporter was developed. The peptide binds to the dopamine- and cocaine-binding site of the dopamine transporter and has behavioral effects different from those of cocaine in mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzoates / chemical synthesis*
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Benzoates / chemistry
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Benzoates / pharmacology
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Binding Sites
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Biphenyl Compounds / chemical synthesis*
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Biphenyl Compounds / chemistry
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Biphenyl Compounds / pharmacology
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CHO Cells
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Central Nervous System Stimulants / chemical synthesis*
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Central Nervous System Stimulants / chemistry
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Central Nervous System Stimulants / pharmacology
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Cocaine / metabolism
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Conditioning, Psychological / drug effects
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Cricetinae
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Cricetulus
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Dopamine / metabolism
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Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors*
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Dopamine Plasma Membrane Transport Proteins / chemistry
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Dopamine Plasma Membrane Transport Proteins / metabolism
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Mice
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Motor Activity / drug effects
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Naphthalenes / chemical synthesis*
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Naphthalenes / chemistry
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Naphthalenes / pharmacology
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / pharmacology
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Protein Structure, Secondary
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Radioligand Assay
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Rats
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Reward
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Structure-Activity Relationship
Substances
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Benzoates
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Biphenyl Compounds
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Central Nervous System Stimulants
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Dopamine Plasma Membrane Transport Proteins
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Naphthalenes
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Oligopeptides
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Cocaine
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Dopamine