Sandmeyer reaction repurposed for the site-selective, non-oxidizing radioiodination of fully-deprotected peptides: Studies on the endogenous opioid peptide α-neoendorphin Journal Article

   

Authors:	Pickett, J. E.; Nagakura, K.; Pasternak, A. R.; Grinnell, S. G.; Majumdar, S.; Lewis, J. S.; Pasternak, G. W.
Article Title:	Sandmeyer reaction repurposed for the site-selective, non-oxidizing radioiodination of fully-deprotected peptides: Studies on the endogenous opioid peptide α-neoendorphin
Abstract:	Standard radioiodination methods lack site-selectivity and either mask charges (Bolton-Hunter) or involve oxidative reaction conditions (chloramine-T). Opioid peptides are very sensitive to certain structural modifications, making these labeling methods untenable. In our model opioid peptide, α-neoendorphin, we replaced a tyrosyl hydroxyl with an iodine, and in cell lines stably expressing mu, delta, or kappa opioid receptors, we saw no negative effects on binding. We then optimized a repurposed Sandmeyer reaction using copper(I) catalysts with non-redoxing/non-nucleophilic ligands, bringing the radiochemical yield up to around 30%, and site-selectively incorporated radioactive iodine into this position under non-oxidizing reaction conditions, which should be broadly compatible with most peptides. The 125I- and 131I-labeled versions of the compound bound with high affinity to opioid receptors in mouse brain homogenates, thus demonstrating the general utility of the labeling strategy and of the peptide for exploring opioid binding sites. © 2013 Elsevier Ltd. All rights reserved.
Keywords:	unclassified drug; nonhuman; binding affinity; mouse; animal tissue; tyrosine; iodine 125; iodine 131; isotope labeling; binding site; protein structure; mu opiate receptor; catalyst; copper; receptor binding; radiochemistry; iodine; cho cell; i-131; delta opiate receptor; kappa opiate receptor; opiate peptide; i-125; radioiodination; endogenous opioid peptide; opioid receptor binding; peptide radioiodination; alpha neoendorphin; tyrosyl hydroxyl; brain homogenate; sandmeyer reaction
Journal Title:	Bioorganic & Medicinal Chemistry Letters
Volume:	23
Issue:	15
ISSN:	0960-894X
Publisher:	Pergamon-Elsevier Science Ltd
Date Published:	2013-08-01
Start Page:	4347
End Page:	4350
Language:	English
DOI:	10.1016/j.bmcl.2013.05.090
PROVIDER:	scopus
PMCID:	PMC3725135
PUBMED:	23796454
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84879685926&partnerID=40&md5=21252e168846a75aa56b686bc71e7d59
Notes:	"Export Date: 1 August 2013" - "CODEN: BMCLE" - "Source: Scopus"

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