Backbone metal-cyclization: A novel approach for simultaneous peptide cyclization and radiolabeling. Application to the combinatorial synthesis of rhenium-cyclic somatostatin analogs

Gil Fridkin, Thomas A. Bonasera, Pninit Litman, Chaim Gilon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

A novel approach for the combinatorial synthesis of backbone-derived metal-cyclic peptide libraries is presented. In this approach the metalo-cyclic peptides are prepared from their linear precursors through complexation of a metal atom via two hemi-chelating arms located on the peptide backbone. Thus, cyclization and metal labeling of the peptides are achieved simultaneously. A library, composed of 48 rhenium-cyclic somatostatin analogs, was prepared. All rhenium somatostatin complexes exhibited high to moderate in vitro binding affinities toward cloned human somatostatin receptor subtype 2 (hsstr2). Five rhenium-cyclic peptides were found to be most potent with IC50 values between 1 and 3 nM making them promising leads for further development of tumor diagnostic and therapeutic radiolabeled agents. A 99mTc somatostatin cyclic analog was successfully prepared by the same method.

Original languageEnglish
Pages (from-to)39-50
Number of pages12
JournalNuclear Medicine and Biology
Volume32
Issue number1
DOIs
StatePublished - Jan 2005

Keywords

  • Backbone metal-cyclization
  • Radiolabeled somatostatin analogs

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