Synthesis, characterization and biological evaluation of a 67Ga-labeled (η6-Tyr)Ru(η5-Cp) peptide complex with the HAV motif

Zsolt Bihari, Filipe Vultos, Célia Fernandes, Lurdes Gano, Isabel Santos, João D G Correia, P. Buglyó

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Heterobimetallic complexes with the evolutionary, well-preserved, histidyl-alanyl-valinyl (HAV) sequence for cadherin targeting, an organometallic Ru core with anticancer activity and a radioactive moiety for imaging may hold potential as theranostic agents for cancer. Visible-light irradiation of the HAVAY-NH2 pentapeptide in the presence of [(η5-Cp)Ru(η6-naphthalene)]+ resulted in the formation of a full sandwich type complex, (η6-Tyr-RuCp)-HAVAY-NH2 in aqueous solution, where the metal ion is connected to the Tyr (Y) unit of the peptide. Conjugation of this complex to 2,2'-(7-(1-carboxy-4-((4-isothiocyanatobenzyl)amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODA-GA) and subsequent metalation of the resulting product with stable (natGa) and radioactive (67Ga) isotope yielded natGa/67Ga-NODA-GA-[(η6-Tyr-RuCp)-HAVAY-NH2]. The non-radioactive compounds were characterized by NMR spectroscopy and Mass Spectrometry. The cellular uptake and cytotoxicity of the radioactive and non-radioactive complexes, respectively, were evaluated in various human cancer cell lines characterized by different levels of N- or E-cadherins expression. Results from these studies indicate moderate cellular uptake of the radioactive complexes. However, the inhibition of the cell proliferation was not relevant.

Original languageEnglish
JournalJournal of Inorganic Biochemistry
DOIs
Publication statusAccepted/In press - Oct 19 2015

Keywords

  • Cadherin
  • Full sandwich ruthenium complex
  • Gallium complex
  • HAV sequence
  • Oligopeptide conjugate
  • Radiolabeling

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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