Abstract

Natural polyphenols are promising compounds for the pharmacological control of oxidative stress in various diseases. However, low bioavailability and rapid metabolism of polyphenols in a form of glycosides or aglycones have stimulated the search for the vehicles that would provide their efficient delivery to the systemic circulation. Conjugation of polyphenols with cationic amphiphilic peptides yields compounds with a strong antioxidant activity and ability to pass through biological barriers. Due to a broad range of biological activities characteristic of polyphenols and peptides, their conjugates can be used in the antioxidant therapy, including the treatment of viral, oncological, and neurodegenerative diseases. In this work, we synthesized linear and dendrimeric cationic amphiphilic peptides that were then conjugated with gallic acid (GA). GA is a non-toxic natural phenolic acid and an important functional element of many flavonoids with a high antioxidant activity. The obtained GA-peptide conjugates showed the antioxidant (antiradical) activity that exceeded 2-3 times the antioxidant activity of ascorbic acid. GA attachment had no effect on the toxicity and hemolytic activity of the peptides. GA-modified peptides stimulated the transmembrane transfer of the pGL3 plasmid encoding luciferase reporter gene, although GA attachment at the N-terminus of peptides reduced their transfection activity. Several synthesized conjugates demonstrated the antibacterial activity in the model of Escherichia coli Dh5α growth inhibition.

中文翻译：

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含多酚的线性和树枝状阳离子肽的合成和生物学性质

摘要

天然多酚是用于药理学控制各种疾病中氧化应激的有前途的化合物。然而，糖苷或苷元形式的多酚生物利用度低且代谢快速，刺激了对能够将其有效递送至体循环的载体的研究。多酚与阳离子两亲性肽的结合产生具有强抗氧化活性和穿过生物屏障能力的化合物。由于多酚和肽具有广泛的生物活性特征，它们的缀合物可用于抗氧化治疗，包括治疗病毒、肿瘤和神经退行性疾病。在这项工作中，我们合成了线性和树枝状阳离子两亲肽，然后与没食子酸（GA）缀合。 GA是一种无毒的天然酚酸，是多种黄酮类化合物的重要功能元素，具有较高的抗氧化活性。获得的GA-肽缀合物显示出超过抗坏血酸抗氧化活性2-3倍的抗氧化（抗自由基）活性。 GA 连接对肽的毒性和溶血活性没有影响。 GA 修饰的肽刺激编码荧光素酶报告基因的 pGL3 质粒的跨膜转移，尽管肽 N 末端的 GA 连接降低了其转染活性。几种合成的缀合物在大肠杆菌Dh5α 生长抑制模型中表现出抗菌活性。