Generation of novel radiolabeled opiates through site-selective iodination Journal Article


Authors: Majumdar, S.; Burgman, M.; Haselton, N.; Grinnell, S.; Ocampo, J.; Pasternak, A.; Pasternak, G. W.
Article Title: Generation of novel radiolabeled opiates through site-selective iodination
Abstract: Tritiated opioid radioligands have proven valuable in exploring opioid binding sites. However, tritium has many limitations. Its low specific activity and limited counting efficiency makes it difficult to examine low abundant, high affinity sites and its disposal is problematic due to the need to use organic scintillants and its relatively long half-life. To overcome these issues, we have synthesized both unlabeled and carrier-free radioiodinated iodobenzoyl derivatives of 6β-naltrexamine (125I-BNtxA, 18), 6β-naloxamine (125I-BNalA, 19) and 6β-oxymorphamine ( 125I-BOxyA, 20) with specific activities of 2100 Ci/mmol. To optimize the utility of the radioligand, we designed a synthesis in which the radiolabel is incorporated in the last synthetic step, which required the selective iodination of the benzoyl moiety without incorporation into the phenolic A ring. Competition studies demonstrated high affinity of the unlabelled compounds for opioid receptors in transfected cell lines, as did the direct binding of the 125I-ligands to the opioid receptors. The radioligand displayed very high sensitivity, enabling a marked reduction in tissue, as well as excellent signal/noise characteristics. These new 125I-radioligands should prove valuable in future studies of opioid binding sites. © 2011 Elsevier Ltd. All rights reserved.
Keywords: unclassified drug; drug activity; nonhuman; animal cell; animals; opiate; signal noise ratio; cell line; drug receptor binding; iodine 125; isotope labeling; iodine radioisotopes; binding sites; molecular structure; morphine; drug binding site; ligand binding; naloxone; opiate receptor; enkephalin[2,5 dextro penicillamine]; naltrindole; naltrexone; opioid receptor; cho cells; cricetinae; cricetulus; neurotransmitter agents; oxymorphone; binding, competitive; opiate antagonist; radioligand; iodination; 6beta naloxamine; 6beta naltrexamine; 6beta oxymorphamine; dextro phenylalanylcysteinyltyrosyl dextro tryptophylarginylthreonylpenicillaminylthreoninamide 2,7 disulfide; enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine]; levallorphan; radioligand assay; receptors, opioid
Journal Title: Bioorganic & Medicinal Chemistry Letters
Volume: 21
Issue: 13
ISSN: 0960-894X
Publisher: Pergamon-Elsevier Science Ltd  
Date Published: 2011-07-01
Start Page: 4001
End Page: 4004
Language: English
DOI: 10.1016/j.bmcl.2011.05.008
PROVIDER: scopus
PMCID: PMC3115495
PUBMED: 21621410
DOI/URL:
Notes: --- - "Export Date: 9 December 2011" - "CODEN: BMCLE" - "Source: Scopus"
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MSK Authors
  1. Gavril W Pasternak
    306 Pasternak