Department of Chemistry, Ben-Gurion University of the Negev, P.O. Box 653, Be'er Sheva 84105, Israel.
Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Be'er-Sheva 84105, Israel.
Inorg Chem. 2021 Jan 4;60(1):484-493. doi: 10.1021/acs.inorgchem.0c03350. Epub 2020 Dec 15.
The concept of metal chelation is based on simple coordination chemistry. The development of an ideal metal chelator that completely and selectively removes toxic metals from a specific metal binding site in proteins is required to prevent and or inhibit a variety of diseases, among them neurodegenerative diseases. This work examines neuropeptide Y (NPY) as a Zn and Cu chelator agent. NPY is a natural peptide that is produced in the human body; therefore, it is not a toxic agent and the complex that it forms is not toxic as well. Our simulations reveal that NPY has an efficient Zn chelation activity but is less effective in chelating Cu. Moreover, while NPY demonstrates several conformations, the metal chelation occurs more efficiently in its native structure. Beyond the exploration of the activity of NPY as a Zn and Cu chelator agent, this work provides an insight into the molecular mechanisms of the chelation of these metals at the molecular level. The outcomes from this work may guide future experimental studies to examine NPY in metal chelation therapy for neurodegenerative diseases.
金属螯合的概念基于简单的配位化学。为了预防和/或抑制多种疾病，包括神经退行性疾病，需要开发一种理想的金属螯合剂，该螯合剂能完全且选择性地从蛋白质中特定的金属结合位点去除有毒金属。本研究考察了神经肽 Y（NPY）作为 Zn 和 Cu 的螯合剂。NPY 是一种天然存在于人体内的肽，因此它不是有毒物质，它所形成的配合物也没有毒性。我们的模拟表明，NPY 具有有效的 Zn 螯合活性，但对 Cu 的螯合效果较差。此外，虽然 NPY 表现出多种构象，但金属螯合在其天然结构中更有效。除了探索 NPY 作为 Zn 和 Cu 螯合剂的活性外，本研究还深入了解了这些金属在分子水平上螯合的分子机制。这项工作的结果可能为未来的实验研究提供指导，以研究 NPY 在神经退行性疾病的金属螯合治疗中的作用。
