Abstract
In this paper, we describe the synthesis of novel endomorphin-2 analogs, containing N-methylated amino acids, consecutively in each position. The receptor-binding profile of the new analogs and their stability against enzymatic cleavage by commercially available peptidases, carboxypeptidase Y and aminopeptidase M, and a rat brain homogenate are reported. The best analog of this series, [Sar2]endomorphin-2, was almost equipotent with the parent peptide in the mu-receptor-binding assay and was also highly resistant to enzymatic degradation. This analog may be a suitable candidate for the in vivo antinociceptive studies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkylation
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Amino Acids / metabolism*
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Aminopeptidases / metabolism
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Animals
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Brain / enzymology
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CD13 Antigens
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Cathepsin A / metabolism
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Enzyme Stability / physiology
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Kinetics
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Ligands
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Methionyl Aminopeptidases
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Methylation
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Oligopeptides / chemistry
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Oligopeptides / metabolism*
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Protein Binding
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Protein Conformation
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Rats
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Receptors, Opioid, mu / agonists
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Receptors, Opioid, mu / metabolism
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Structure-Activity Relationship
Substances
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Amino Acids
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Ligands
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Oligopeptides
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Receptors, Opioid, mu
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endomorphin 2
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Aminopeptidases
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Methionyl Aminopeptidases
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CD13 Antigens
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Cathepsin A