A potentiometric and spectroscopic study of the interaction of the N terminal tetrapeptide fragment of fibrinopeptide A with CuII and NiII

Abstract

The syntheses are reported of the amino-terminal tetrapeptide fragment of human fibrinopeptide A (Ala-Asp-Ser-Gly) and derivative tetrapeptides with the β-carboxylate of the aspartate residue and the hydroxy group of the serine residue blocked to prevent co-ordination to metal ions. Complexes with hydrogen ion and copper(II), and in the case of Ala-Asp-Ser-Gly with nickel(II) also, have been studied by a combined approach of potentiometric and spectroscopic [absorption, circular dichroism, e.s.r. and, with nickel(II), ¹H n.m.r.] techniques. Stability constants of copper(II) and nickel(II) complexes of ‘tetra-alanine’(Ala-Ala-Ala-Ala) have also been measured. The β-carboxylate group has been shown to co-ordinate strongly to Cu^II over the pH range 4–9 to give an unusually stable [CuH_–1L] species (overall charge omitted). Fibrinopeptide A, which is present in locally high concentrations near the sites of bodily injury, would similarly be expected to co-ordinate strongly to Cu^II.