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 method s reveal novel interactions of endothelin A selective receptor antagonists, cyclo(D-Trp-D-Asp-Pro-D-Val-Leu), cyclo(D-Trp-D-Glu-Ala-D-allo-Ile-Leu) an d 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 adduct s and sandwich structures: [M + Na](+), [M + 2Na - H](+), [M + 3Na - 2H](+) , [M + 4Na - 3H](+), [M + 5Na - 4H](+), [2M + Na](+), [2M + 2Na - H](+), [2 M + 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 obse rved sodium binding properties may have implications in understanding their protective effects against ischemia-induced acute renal failure. Those cyc lic peptides that offer protection may be those that have high affinities f or multiple sodium ions. (C) 1999 Academic Press.