Novel sodium binding properties of some cyclopentapeptide endothelin a selective receptor antagonists: Electrospray and fast-atom-bombardment mass spectrometric studies

Electrospray ionization and fast atom bombardment mass spectrometric methods reveal novel interactions of endothelin A selective receptor antagonists, cycle (D-Trp-D-Asp-Pro-D-Val-Leu), cyclo(D-Trp-D-Glu-Ala-D-allo-Ile-Leu) and cyclo(D-Trp-D-Asp-Pro-D-Ile-Leu) with sodium ions. The peptides have very high intrinsic affinities for sodium ions, and form multiple sodium adducts and sandwich structures: [M + Na]⁺, [M + 2Na - H]⁺, [M + 3Na - 2H]⁺, [M + 4Na - 3H]⁺, [M + 5Na - 4H]⁺, [2M + Na]⁺, [2M + 2Na - H]⁺, [2M + 3Na - 2H]⁺, [2M + 4Na - 3H]⁺, [2M + 5Na - 4H]⁺, [2M + 6Na - 5H]⁺, and [2M + 7Na - 6H]⁺. The three cyclic peptides exhibit similar sodium binding stoichiometries despite differences in their amino acids. The observed sodium binding properties may have implications in understanding their protective effects against ischemia-induced acute renal failure. Those cyclic peptides that offer protection may be those that have high affinities for multiple sodium ions.