Radioiodinated azide and isothiocyanate derivatives of cocaine for irreversible labeling of dopamine transporters: Synthesis and covalent binding studies

John R. Lever, Mu Fa Zou, M. Laura Parnas, Romain A. Duval, Sara E. Wirtz, Joseph B. Justice, Roxanne A. Vaughan, Amy Hauck Newman

Research output: Contribution to journalArticle

Abstract

Two novel N-substituted-3β-phenyltropane alkaloids have been labeled with iodine-125 for use as irreversible probes of dopamine transporter (DAT) binding sites. One contains an iodoaryl azide moiety for photolabeling, while the other bears an iodoaryl isothiocyanate for direct conjugation. Both radioligands were prepared in a one-flask procedure by electrophilic radioiodination of the corresponding aniline under no-carrier-added conditions, followed either by diazotization and treatment with sodium azide, or by addition of thiophosgene under basic conditions. Specifically, (-)-N-[4-(3-[ 125I]iodo-4-azidophenyl)butyl]-2β-carbomethoxy-3β-(4- chlorophenyl)tropane ([125I]MFZ-2-24) and (-)-N-[4-(3-[ 125I]iodo-4-isothiocyanophenyl)butyl]-2β-carbomethoxy-3β- (4-chlorophenyl)tropane ([125I]MFZ 3-37) were synthesized. Isolation by reversed-phase HPLC and solid-phase extraction gave good average yields of [125I]MFZ-2-24 (67%, n = 5) and [125I]MFZ-3-37 (45%, n = 3) with high radiochemical purities (96-99%) and specific radioactivities (>2000 mCi/μmol). The utility of the radioligands was demonstrated by their covalent linkage to rat striatal membranes, and immunoprecipitation of a single radiolabeled band at 80 kDa corresponding to the full-length DAT.

Original languageEnglish (US)
Pages (from-to)644-649
Number of pages6
JournalBioconjugate Chemistry
Volume16
Issue number3
DOIs
StatePublished - May 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

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