Department of Inorganic Chemistry, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Laboratory of Elemental Analysts and Structural Research, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Int J Mol Sci. 2021 Dec 30;23(1):418. doi: 10.3390/ijms23010418.
Mucin 7 (encoded byMUC7) is a human salivary protein that has a role in the natural immune system. Fragments of mucin 7 exhibit antimicrobial activity against bacteria and yeast. Although the antimicrobial properties of peptides have been known and studied for decades, the exact mechanism of action of antimicrobial peptides (AMPs) is still unclear. It is known that some AMPs require divalent metal ions to activate their activity. Herein, we investigated three 15-mer MUC7 peptides, one of which (mother peptide, sequence, L3) is a synthetic analog of a fragment naturally excised from MUC7 (with His3, His8, and His 14) and its two structural analogs, containing only two histidine residues, His3, His13 and His8, His13 (L2 and L1, respectively). Since there is a correlation between lipophilicity, the presence of metal ions (such as Cu(II) and Zn(II)) and antimicrobial activity of AMP, antimicrobial properties of the studied peptides, as well as their complexes with Cu(II) and Zn(II) ions, were tested for activity against Gram-positive (, ) and Gram-negative (, ) bacteria and fungi (). The results were correlated with their lipophilicity. Coordination and thermodynamic studies (potentiometry, UV-Vis, CD) revealed the formation of mainly mononuclear complexes in solution for all studied systems with different stability in the physiological pH range.
黏蛋白 7(由 MUC7 编码)是一种人类唾液蛋白,在天然免疫系统中发挥作用。黏蛋白 7 的片段对细菌和酵母表现出抗菌活性。尽管肽的抗菌特性已经为人所知并研究了几十年,但抗菌肽(AMPs)的确切作用机制仍不清楚。已知一些 AMP 需要二价金属离子来激活其活性。在此,我们研究了三种 15 肽 MUC7 肽,其中一种(母肽,序列为 L3)是从 MUC7 天然切除的片段(带有 His3、His8 和 His14)及其两个结构类似物的合成类似物,仅包含两个组氨酸残基,His3、His13 和 His8、His13(分别为 L2 和 L1)。由于亲脂性、金属离子(如 Cu(II) 和 Zn(II))的存在与 AMP 的抗菌活性之间存在相关性,因此研究了这些肽及其与 Cu(II) 和 Zn(II) 离子的复合物对革兰氏阳性( 、 )和革兰氏阴性( 、 )细菌和真菌( )的抗菌活性。结果与它们的亲脂性相关。配位和热力学研究(电位法、UV-Vis、CD)表明,在所研究的所有系统中,在生理 pH 范围内形成了主要为单核配合物的溶液,其稳定性不同。