Research Article
RodrÃÂÂguez-Fragoso Lourdes,
Abstract
Non-covalent metal-peptide interactions are critical in peptide assembly, folding, stability, and function. Zinc has chemical, structural and regulatory functions in biological systems. The present study investigated the changes caused by the addition of Zn2+ on the biological activity of a thymic peptide on immune cells. For this purpose, we exposed different cells to 10-10 M peptide and different concentrations of Zn2+, Mg2+ and Cu2+ for 24 and 48 h, and monitored the proliferative and phagocytic activities of the treated cells. We also performed NMR and chromatography analysis of the peptide in the presence of Zn2+ and other ions. Peptide activity increased in the presence of Zn2+, Mg2+ or Cu2+, and this increase was over 100-fold in the presence of Zn2+. NMR studies indicated that the peptide exhibited field displacements: Glutamic acid (D) to low-field NMR (Δδ+0.027 ppm), and both aspartic acid (E) and the leucine with a terminal carboxylic acid (L8) to high-field NMR (Δδ-0.016 and -0.051 ppm, respectively). In addition, the retention time in HPLC decreased in the presence of ions. Our findings show that the peptide loses its biological activity in the presence of a zinc-chelating agent. That is, the presence of zinc and other metals to a lesser extent is essential for the activity of the peptide. This unexpected dependence on zinc appears to be due to the active form of the peptide-zinc complex, for which we propose the name of “immuno-modulator metallo-peptide” (IMMP).