Synthesis of novel 1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA) derivatives for chemoselective attachment to unprotected polyfunctionalized compounds

Sebastian Knör, Armin Modlinger, Thorsten Poethko, Margret Schottelius, Hans Jürgen Wester, Horst Kessler

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

A convenient synthesis of novel bifunctional poly(amino carboxylate) chelating agents allowing chemoselective attachment to highly functionalized biomolecules is described. Based on the well known chelator 1,4,7,10- tetraazacyclodecane-l,4,7,10-tetraacetic acid (DOTA), we synthesized novel bifunctional chelating agents bearing additional functional groups by alkylating 1,4,7,10-tetraazacyclododecane (cyclen) with one equivalent of para-functionalized alkyl 2-bromophenyl-acetate and three equivalents of tert-butyl 2-bromoacetate. The resulting compounds, which contain an additional carbonyl or alkyne functionality, allow site specific labeling of appropriately functionalized unprotected biomolecules in a rapid manner via click reactions. This was demonstrated by the attachment of our new DOTA derivatives to the somatostatin analogue Tyr3-octreotate by chemoselective oxime ligation and CuI-catalyzed azide-alkyne cycloaddition. Initial biodistribution studies in mice with the radiometalated compound demonstrated the applicability of the described DOTA conjugation.

Original languageEnglish
Pages (from-to)6082-6090
Number of pages9
JournalChemistry - A European Journal
Volume13
Issue number21
DOIs
StatePublished - 2007

Keywords

  • Antitumor agents
  • Click reactions
  • Isotopic labeling
  • Oxime ligation

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