Synthesis and characterization of 1,1,4,4-butanetetracarboxylic acid : a di-γ-carboxyglutamic acid (GlaGla) analogue

1,1,4,4-Butanetetracarboxylic acid (BTCA) is evaluated as an analogue for the metal binding site in dipeptides of gamma-carboxyglutamic acid (Gla). Molecular modeling suggests that the four carboxylic acid groups in BTCA can assume a similar conformation to the four gamma-carboxylic acid groups in GlaGla and thus provides the impetus for the synthesis and metal binding determinations. BTCA is synthesized via the tert.-butyl ester and characterized via NMR, mass spectroscopy, and elemental composition. Equilibrium binding constants with protons, Ca(II) and Mg(II) are determined via pH and Ca(II) ion-selective electrode titrations and are found to be similar to those for GlaGla peptides with blocked termini.