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Multiple Ligands in Opioid Research

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The observation in 1979 that opioid receptors interact, led to the design of bivalent ligands in an attempt to improve selectivity and affinity towards the different subtypes (i.e. μ, δ and κ). Dimers of monovalent “parent” opioid structures have been evaluated and include: (a) endogenous (e.g. enkephalins) or exogenous (e.g. dermorphin) peptide dimer analogues (b) mixed peptidic-non-peptidic bivalent ligands and (c) dual non-peptidic dimers. Chimeric structures, using an opioid pharmacophore in combination with a non-opioid pharmacophore, have also been prepared. The common aim in all these studies is to improve the pharmacological profile of potential analgesics to minimize common opioid-induced side-effects, such as physical dependence and tolerance. Here we present a brief overview of efforts to develop bivalent opioid ligands for use in pain-related research.

Keywords: Opioid system; bivalent ligands; receptor dimer complexes

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986608785133672

Publication date: July 1, 2008

More about this publication?
  • Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.
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