Shoshan Michal S
University of Zurich, Department of Chemistry, Winterthurerstrasse 190, CH-8057 Zürich.
Chimia (Aarau). 2022 Sep 21;76(9):744-747. doi: 10.2533/chimia.2022.744.
It will soon be twenty years since the last chelating agent was clinically approved to be used against toxic metals. Even though metal poisoning has been known to humankind for centuries, only about a dozen compounds, all of which are small molecules, compose the pharmaceutical toolbox to expel intrinsically toxic or essential but misregulated metals. These compounds widely suffer from various drawbacks, most critically, poor metal selectivity. Can medicinal inorganic chemistry offer modern solutions to these old challenges? In this perspective, the opportunities and advantages of harnessing short peptides for chelation therapy are described. While broadly aiming to address various toxic metals, achievements in targeting lead (Pb) with peptides reveal the unexplored potential hidden in this chemical space and raise the possibility that peptides may reform chelation therapy.
自上一种螯合剂被临床批准用于对抗有毒金属以来,很快就将迎来二十周年。尽管金属中毒在人类中已为人所知数百年,但用于排出内在有毒或必需但调节不当的金属的药物工具箱中只有大约十二种化合物,而且都是小分子。这些化合物普遍存在各种缺点,最关键的是金属选择性差。药物无机化学能否为这些老问题提供现代解决方案?从这个角度出发,本文描述了利用短肽进行螯合治疗的机会和优势。在广泛致力于解决各种有毒金属问题的同时,用肽靶向铅(Pb)的研究成果揭示了这个化学空间中隐藏的未被探索的潜力,并增加了肽可能革新螯合治疗的可能性。