Zinc complexes of aminoacids and peptides, 11. Solution behaviour and zinc complexation of tripeptide with cysteine and/or histidine at both termini

Eight tripeptides and one tetrapeptide with cysteine and/or histidine at both termini were synthesized. They were fully protected (acetyl at the N terminus and ester or amide at the C terminus), making cysteine thiolate and histidine imidazole the only donor functions. The central amino acids (valine, proline, and the non-natural amino acid (S)-3-amino-2-oxo-1N-pyrrolidineacetic acid, Apa) were chosen such that they support or strongly favour a folding of the peptide chain in this position. Potentiometric measurements have shown that all these peptides form 1:1 zinc complexes in solution and that the bis-cysteinyl peptides also form 2:2 complexes. In these complexes the peptide is a chelating ligand forming 12- to 17-membered chelate rings. A comparative discussion of complex stabilities reveals that the peptides containing valine in the central position do not provide additional stability to their zinc complexes by means of protein folding, e.g. by a beta-turn. Proline, and more pronouncedly the non-natural amino acid Apa, however, exert this type of complex stability enhancement by preoganization. (C) 1998 Elsevier Science S.A. All rights reserved.