Copper(II) complexation by pituitary adenylate cyclase activating polypeptide fragments

Results are reported from potentiometric and spectroscopic (UV-Vis, CD, and ESR) studies of the protonation constants and Cu2+ complex stability const ants of pituitary adenylate cyclase activating polypeptide fragments (HSDGI -NH2, TDSYS-NH2, RKQMAVKKYLAAVLNH(2)). With HSDGI-NH2, the formation of a d imeric complex Cu2H-2L2 was found in the pH range 5-8, in which the coordin ation of copper(II) is glycylglycine-like, while the fourth coordination si te is occupied by the imidazole N-3 nitrogen atom, forming a bridge between two copper(II) ions. The formation of dimeric species does not prevent the deprotonation and coordination of the amide nitrogen, and in pH above 8 th e CuH-2L complex is formed. Aspartic acid in the third position of peptide sequence stabilizes the CuH-2L species and prevents the coordination of a f ourth nitrogen donor. Aspartic acid residue in the second position of TDSYS -NH2 stabilizes the Cut (2N) complex but does nor prevent deprotonation and binding of the second and third peptide nitrogens to give 3N and 3N comple xes at higher pH. The tetradecapeptide amide forms with copper(II) ions unu sually stable 3N and 4N complexes compared to pentaalanine amide. (C) 1999 Elsevier Science Inc. All rights reserved.