Interaction of calcium ions with peptide hormones of the gastrin family

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Abstract
The interactions of Des‐Trp1‐Nle12‐minigastrin I (Nle11‐HG‐13) and Nle15‐little gastrin I (Nle15‐HG‐17) with calcium ions have been investigated in water and in trifluoroethanol solution using uv and CD absorption techniques. Both hormones strongly interact with Ca2+ in the organic medium. In the case of Nle11‐HG‐13, the near‐uv chiroptical properties (dominated by the transitions of the Trp residue in the C‐terminal tetrapeptide sequence) indicate that three metal ions per mole of hormone are involved in the binding process. From the different response of near‐uv and far‐uv CD properties to the addition of calcium and from the change of the CD spectra in the aromatic absorption region, it is concluded that the biologically important C‐terminal sequence is directly involved in the interaction with calcium. Elongation of the peptide chain from Nle11‐HG‐13 to Nle15‐HG‐17 (Nle15‐little gastrin I) does not provide any additional binding site for calcium ions. The change of the CD properties in the near‐ and far‐uv indicates that three metal ions per mole of hormone are involved in the binding process. The dichroic absorption in the aromatic region indicates that only one of the two Trp residues of the little gastrin analog is sensitive to the presence of calcium. On the assumption that the variation of the CD properties is proportional to the extent of calcium binding, the binding constants K1, K2, and K3 have been estimated roughly. Two similar sets of binding constants have been found, with K1 ≥ 106M−1 and K3 of the order of 105M−1, indicating similar binding sites in the two hormones with high affinity for calcium ions.