Miller Adriana, Matera-Witkiewicz Agnieszka, Mikołajczyk-Tarnawa Aleksandra, Kola Arian, Wiloch Magdalena, Jonsson-Niedziolka Martin, Wieczorek Robert, Wątły Joanna, Valensin Daniela, Rowińska-Żyrek Magdalena
Faculty of Chemistry, University of Wrocław ul. F. Joliot-Curie 14 50-383 Wrocław Poland
Screening of Biological Activity Assays and Collection of Biological Material Laboratory, Wrocław Medical University Biobank, Faculty of Pharmacy, Wrocław Medical University ul. Borowska 211A 50-556 Wrocław Poland.
Chem Sci. 2025 Jan 23;16(8):3447-3458. doi: 10.1039/d4sc05222f. eCollection 2025 Feb 19.
PvHCt, a 23-amino acid long, histidine-rich peptide derived from shrimp, becomes strongly antimicrobial upon Cu(ii) ion binding. We describe Zn(ii) and Cu(ii) complexes of this peptide, aiming to understand how metal binding and structure correlates to biological activity. Using NMR, UV-vis, CD and FTIR spectroscopies, along with cyclic voltammetry, potentiometry, and DFT calculations, we demonstrate that Cu(ii) binds to the central and C-terminal regions of the peptide, inducing significant structural changes. These include a pronounced bend in the peptide backbone, increased α-helical content, and the production of reactive oxygen species, all of which contribute to the remarkable antimicrobial potency of PvHCt. In contrast, Zn(ii) binds to the C-terminal region with minimal impact on the peptide's overall structure, failing to enhance its antimicrobial activity.
PvHCt是一种源自虾的富含组氨酸的23个氨基酸长的肽，在与铜（II）离子结合后具有很强的抗菌活性。我们描述了这种肽的锌（II）和铜（II）配合物，旨在了解金属结合和结构与生物活性之间的关系。通过核磁共振（NMR）、紫外可见光谱（UV-vis）、圆二色光谱（CD）和傅里叶变换红外光谱（FTIR），以及循环伏安法、电位滴定法和密度泛函理论（DFT）计算，我们证明铜（II）与肽的中央和C端区域结合，诱导了显著的结构变化。这些变化包括肽主链明显弯曲、α-螺旋含量增加以及活性氧的产生，所有这些都有助于PvHCt显著的抗菌效力。相比之下，锌（II）与C端区域结合，对肽的整体结构影响最小，未能增强其抗菌活性。
