High Affinity Binding of Indium and Ruthenium Ions by Gastrins

Journal Article · 11 October 2015 · PLoS ONE

DOI: https://doi.org/10.1371/journal.pone.0140126 · OSTI ID:1903985

Baldwin, Graham S. ^[1]; George, Graham N. ^[2]; Pushie, M. Jake ^[2]

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1. Univ. of Melbourne, VIC (Australia); OSTI
2. Univ. of Saskatchewan, Saskatoon, SK (Canada)

The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated forms of the hormone. Since gastrins act as growth factors in gastrointestinal cancers, and as peptides labelled with Ga and In isotopes are increasingly used for cancer diagnosis, the ability of gastrins to bind other metal ions was investigated systematically by absorption spectroscopy. The coordination structures of the complexes were characterized by extended X-ray absorption fine structure (EXAFS) spectroscopy. Changes in the absorption of gastrin in the presence of increasing concentrations of Ga³⁺ were fitted by a 2 site model with dissociation constants (K_d) of 3.3 x 10^-7 and 1.1 x 10^-6 M. Although the absorption of gastrin did not change upon the addition of In³⁺ ions, the changes in absorbance on Fe³⁺ ion binding in the presence of indium ions were fitted by a 2 site model with Kd values for In³⁺ of 6.5 x 10^-15 and 1.7 x 10^-7 M. Similar results were obtained with Ru³⁺ ions, although the K_d values for Ru³⁺ of 2.6 x 10^-13 and 1.2 x 10^-5 M were slightly larger than observed for In³⁺. The structures determined by EXAFS all had metal:gastrin stoichiometries of 2:1 but, while the metal ions in the Fe, Ga and In complexes were bridged by a carboxylate and an oxygen with a metal-metal separation of 3.0–3.3 Å, the Ru complex clearly demonstrated a short range Ru—Ru separation, which was significantly shorter, at 2.4 Å, indicative of a metal-metal bond. We conclude that gastrin selectively binds two In³⁺ or Ru³⁺ ions, and that the affinity of the first site for In³⁺ or Ru³⁺ ions is higher than for ferric ions. Some of the metal ion-gastrin complexes may be useful for cancer diagnosis and therapy.

• Research Organization: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
• Sponsoring Organization: National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)
• Grant/Contract Number: AC02-76SF00515
• OSTI ID: 1903985
• Journal Information: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 10 Vol. 10; ISSN 1932-6203
• Publisher: Public Library of ScienceCopyright Statement
• Country of Publication: United States
• Language: English