Abstract
The optimization and truncation of our lead peptide-derived ligand TY005 possessing eight amino-acid residues was performed. Among the synthesized derivatives, NP30 (Tyr(1)-DAla(2)-Gly(3)-Phe(4)-Gly(5)-Trp(6)-O-[3',5'-Bzl(CF3)2]) showed balanced and potent opioid agonist as well as substance P antagonist activities in isolated tissue-based assays, together with significant antinociceptive and antiallodynic activities in vivo.
Keywords:
Bifunctional compounds; NMR structure; Neutokinin-1 receptor antagonists; Opioid receptor agonists; Truncation of peptide sequence.
Published by Elsevier Ltd.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Sequence
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Analgesics / chemistry
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Analgesics / pharmacology
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Analgesics / therapeutic use
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Animals
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Humans
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Ligands
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Neurokinin-1 Receptor Antagonists / chemistry*
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Neurokinin-1 Receptor Antagonists / pharmacology*
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Neurokinin-1 Receptor Antagonists / therapeutic use
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Peptides / chemistry*
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Peptides / pharmacology*
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Peptides / therapeutic use
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Rats
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Receptors, Neurokinin-1 / metabolism
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Receptors, Opioid, delta / agonists*
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, mu / agonists*
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Receptors, Opioid, mu / metabolism
Substances
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Analgesics
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Ligands
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Neurokinin-1 Receptor Antagonists
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Peptides
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Receptors, Neurokinin-1
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Receptors, Opioid, delta
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Receptors, Opioid, mu