抗菌肽是存在于易于感染的生物表面上的短阳离子肽。它们在先天免疫中起着重要作用。这些肽,像其他具有抗菌活性的化合物一样,通常具有显着的超氧化物歧化酶(SOD)活性。我们研究的一个方向是模拟CuZnSOD酶的肽的表征及其生物活性的测定,这些结果可能有助于新型抗菌肽的开发。在本研究的框架下,我们合成了10、15和16元模型肽,其中包含与CuZnSOD酶的Cu(II)和Zn(II)结合位点相对应的氨基酸序列,即Zn(II)结合HVGD序列(80-83.碎片),Cu(II)结合序列HVH(片段46-48),和组氨酸(His63),连接两个金属离子作为咪唑酯桥:Ac-FHVHEGPHFN-NH2(L1(10)),Ac-FHVHAGPHFNGGHVG-NH2(L2(15)),和Ac-FHVHEGPHFNGGHVGD-NH2(L3(16))。pH-电位计,UV-Viss-,和Cu(II)的CD光谱学研究,Zn(II),并进行了这些肽的Cu(II)-Zn(II)混合复合物,并测定了配合物的SOD活性。通过CD光谱法鉴定了Cu(II)和Zn(II)优选的结合位点。从这些系统获得的结果来看,可以得出结论,在等摩尔溶液中,肽的-(NGG)HVGD-序列是铜(II)离子的优选结合位点。然而,在两种金属离子的存在下,根据天然酶,-HVGD-序列提供了Zn(II)的主要结合位点,而大部分Cu(II)与-FHVH-序列结合。根据SOD活性测定,15元和16元肽的复合物具有显着的SOD活性。尽管该活性小于天然CuZnSOD酶的活性,与其他SOD模拟物相比,该复合物在降解超氧阴离子方面表现出更好的性能。因此,模拟CuZnSOD酶的特定氨基酸序列的掺入增加了超氧阴离子催化分解的模型系统的效率。
Antimicrobial peptides are short cationic peptides that are present on biological surfaces susceptible to infection, and they play an important role in innate immunity. These peptides, like other compounds with antimicrobial activity, often have significant superoxide dismutase (SOD) activity. One direction of our research is the characterization of peptides modeling the
CuZnSOD enzyme and the determination of their biological activity, and these results may contribute to the development of novel antimicrobial peptides. In the framework of this research, we have synthesized 10, 15, and 16-membered model peptides containing the amino acid sequence corresponding to the Cu(II) and Zn(II) binding sites of the
CuZnSOD enzyme, namely the Zn(II)-binding HVGD sequence (80-83. fragments), the Cu(II)-binding sequence HVH (fragments 46-48), and the histidine (His63), which links the two metal ions as an imidazolate bridge: Ac-FHVHEGPHFN-NH2 (L1(10)), Ac-FHVHAGPHFNGGHVG-NH2 (L2(15)), and Ac-FHVHEGPHFNGGHVGD-NH2 (L3(16)). pH-potentiometric, UV-Vis-, and CD-spectroscopy studies of the Cu(II), Zn(II), and Cu(II)-Zn(II) mixed complexes of these peptides were performed, and the SOD activity of the complexes was determined. The binding sites preferred by Cu(II) and Zn(II) were identified by means of CD-spectroscopy. From the results obtained for these systems, it can be concluded that in equimolar solution, the -(NGG)HVGD- sequence of the peptides is the preferred binding site for copper(II) ion. However, in the presence of both metal ions, according to the native enzyme, the -HVGD- sequence offers the main binding site for Zn(II), while the majority of Cu(II) binds to the -FHVH- sequence. Based on the SOD activity assays, complexes of the 15- and 16-membered peptide have a significant SOD activity. Although this activity is smaller than that of the native
CuZnSOD enzyme, the complexes showed better performance in the degradation of superoxide anion than other SOD mimics. Thus, the incorporation of specific amino acid sequences mimicking the
CuZnSOD enzyme increases the efficiency of model systems in the catalytic decomposition of superoxide anion.