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Bioinorganic Chemistry Meets Microbiology: Copper(II) and Zinc(II) Complexes Doing the Cha-Cha with the C-t-CCL-28 Peptide, Dancing till the End of Microbes
Inorganic Chemistry ( IF 4.3 ) Pub Date : 2024-10-01 , DOI: 10.1021/acs.inorgchem.4c02500
Klaudia Szarszoń, Natalia Baran, Paulina Śliwka, Magdalena Wiloch, Tomasz Janek, Joanna Wątły

The necessity to move away from conventional antibiotic therapy has sparked interest in antimicrobial peptides (AMPs). One fascinating example is human CCL-28 chemokine produced by acinar epithelial cells in the salivary glands. It can also be released into the oral cavity with saliva, playing a crucial role in oral protection. The C-terminal domain of CCL-28 possesses antifungal and antibacterial properties, which are likely linked to membrane disruption and enzyme leakage. Studies suggest that AMPs can become more potent after they have bound Cu(II) or Zn(II). In many cases, these ions are essential for maximizing effectiveness by altering the peptides’ physicochemical properties, such as their local charge or structure. The examined peptide binds Cu(II) and Zn(II) ions very effectively, forming equimolar complexes. Metal ion binding affinity, coordination mode, and antimicrobial activity strongly depend on the pH of the environment. Coordination modes have been proposed based on the results of potentiometric titrations, spectroscopic studies (UV–visible, electron paramagnetic resonance and circular dichroism at different path lengths), and mass spectrometry. The antimicrobial properties of the Cu(II) and Zn(II) complexes with the C-terminal fragment of CCL-28 chemokine have been assessed against fungal and bacterial strains, demonstrating exceptional activity against Candida albicans at pH 5.4. Moreover, the complex with Zn(II) ions shows the same activity against theStreptococcus mutans bacterium as chloramphenicol, a commonly used antibiotic. Cyclic voltammetry proposed a probable antimicrobial mechanism of the studied Cu(II) complex through the formation of reactive oxygen species, which was also confirmed by tests with ascorbic acid in UV–vis and fluorescence spectroscopic studies.

中文翻译:


生物无机化学与微生物学相遇:铜 (II) 和锌 (II) 络合物与 C-t-CCL-28 肽进行恰恰,跳舞直到微生物的终结



摆脱传统抗生素治疗的必要性引发了人们对抗菌肽 (AMP) 的兴趣。一个有趣的例子是唾液腺中腺泡上皮细胞产生的人类 CCL-28 趋化因子。它也可以随唾液释放到口腔中,在口腔保护中起着至关重要的作用。CCL-28 的 C 端结构域具有抗真菌和抗菌特性,这可能与膜破坏和酶泄漏有关。研究表明,AMP 在结合 Cu(II) 或 Zn(II) 后会变得更有效。在许多情况下,这些离子对于通过改变肽的物理化学性质(例如它们的局部电荷或结构)来最大化有效性至关重要。检查的肽非常有效地结合 Cu(II) 和 Zn(II) 离子,形成等摩尔复合物。金属离子结合亲和力、配位模式和抗菌活性在很大程度上取决于环境的 pH 值。根据电位滴定、光谱研究(紫外-可见光、不同光程的电子顺磁共振和圆二色性)和质谱分析的结果,提出了配位模式。已经评估了 Cu(II) 和 Zn(II) 复合物与 CCL-28 趋化因子的 C 端片段的抗菌特性,对真菌和细菌菌株进行了评估,在 pH 值为 5.4 时对白色念珠菌表现出特殊的活性。此外,与 Zn(II) 离子的复合物对变形链球菌表现出与常用抗生素氯霉素相同的活性。 循环伏安法提出了所研究的 Cu(II) 络合物通过形成活性氧的可能抗菌机制,这也通过紫外-可见光和荧光光谱研究中抗坏血酸的测试得到证实。
更新日期:2024-10-01
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