Zinc-induced conformational transitions of acidic peptides: Characterization by circular dichroism and electrospray mass spectrometry

A series of amphiphilic peptides have been synthesized which have a defined chain length and are based either on the dipeptide periodicity Asp-Leu or the tetrapeptide periodicity Leu-Asp-Asp-Leu. Their behavior in the presenc e of low concentrations of metal ions was studied by circular dichroism spe ctroscopy, In pure water, the peptides adopt a random coil conformation. Th e addition of Zn2+ specifically induces a beta-sheet structure for (Asp-Leu )(n) and an alpha-helix structure for (Leu-Asp-Asp-Leu)(n)-Asp. The conform ational transitions are dependent on the chain length: the critical main ch ain length for beta-sheets and alpha-helix formation is between 10 and 24 r esidues, and between 13 and 25 residues, respectively. The addition of NH4 and Mg2+ have no effect, whereas Ca2+ has only a slight effect on the conf ormation. The peptide (Leu-Asp-Asp-Leu)(8)-Asp complexed to Zn2+ was used i n circular dichroism (CD) spectroscopic studies to investigate the self-ass ociation of alpha-helices as a function of the temperature. The Zn2+ comple xes were analyzed by electrospray mass spectrometry, As expected from the C B studies, the binding of Zn2+ is dependent on the chain length. At 0.4 equ iv Zn2+/lAsp, (Leu-Asp-Asp-Leu)(8)-Asp binds a maximum of five zinc ions, w hich is loss than the theoretical value of eight expected from the peptide sequence. (Leu-Asp-Bsp-Leu)(6)-Asp and (Leu-Asp-Asp-Leu)(3)-Asp bind two an d one zinc ions. respectively, without the formation of an alpha-helix.