Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy.
Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland.
Dalton Trans. 2024 Jul 30;53(30):12676-12687. doi: 10.1039/d4dt01514b.
Antimicrobial peptides are promising alternatives to classical antibiotics. Their microbicidal activity can arise from different mechanisms, one of which is known as nutritional immunity and has metal micronutrients and metal-binding biomolecules as its main players. Calcitermin is an antimicrobial peptide and an effective metal chelator. Its properties as an antibacterial and anti- agent have been recently studied both as a free peptide and in the presence of zinc and copper ions, with which it forms stable complexes. Calcitermin derivatives have also gained attention thanks to the possibility of improving their properties, like metal-binding affinity and/or stability in biological fluids, through modifications of the native peptide sequence. In this work, the Ala-to-Ser substitutions close to the coordination site of calcitermin have been introduced to study the impact on the biological activity and metal-binding properties. Our results show that metal coordination has a clear impact on the bioactivity of the studied compounds, to the point that the truncated fragment of calcitermin, solely containing the main metal-binding residues, also shows antimicrobial activity.
抗菌肽是有前途的替代传统抗生素的方法。它们的杀菌活性可以来自不同的机制，其中一种被称为营养免疫，其主要参与者是微量金属营养元素和金属结合生物分子。降钙素是一种抗菌肽，也是一种有效的金属螯合剂。最近，人们研究了它作为一种游离肽以及在锌和铜离子存在下的作为一种抗菌剂和抗剂的特性，它与这些离子形成稳定的复合物。降钙素衍生物也受到了关注，因为通过对天然肽序列的修饰，可以提高它们的性质，如金属结合亲和力和/或在生物流体中的稳定性。在这项工作中，靠近降钙素配位位点的 Ala-to-Ser 取代被引入，以研究其对生物活性和金属结合性质的影响。我们的结果表明，金属配位对所研究化合物的生物活性有明显的影响，以至于仅含有主要金属结合残基的降钙素的截断片段也表现出抗菌活性。
