Metal ion effects on the cis/trans isomerization equilibrium of proline in short-chain peptides: a solution NMR study

The effect of copper(II) ions on the probabilities of existence of the four detectable conformers of the tetrapeptide Tyr-Pro-Phe-Pro (beta-casomorphin 4) in [2H6]DMSO was investigated by 1H NMR spectroscopy. Integration of the Phe-NH signals provided the relative populations in the free state as tt/tc/ct/cc=28:34:29:9 at 293 K (c=cis, t=trans). Copper(II) was shown to bind to all four isomers, yielding complexes with two different structures, depending on the conformation of Pro(2). The interpretation of paramagnetic relaxation rates of Pro(2)-Halpha signals provided the corresponding isomeric probabilities in the metal-bound state as 13:36:20:31. The observed stabilization of the conformation with the lowest probability of existence (cc) may be relevant for the biological role of copper and other metal ions.