Han Zhenbin, Feng Dongmei, Wang Wenxuan, Wang Yue, Cheng Maosheng, Yang Huali, Liu Yang
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
ACS Omega. 2023 Oct 27;8(44):41876-41884. doi: 10.1021/acsomega.3c06806. eCollection 2023 Nov 7.
Antimicrobial peptides derived from the skin secretions of amphibians have made important progress in tumor therapy due to their unique mechanism of destroying cell membranes. Figainin 1 (F1) is an 18-amino acid antimicrobial peptide from the skin secretions of frogs. In a previous study, F1 was shown to inhibit cancer cell proliferation. F1 is composed entirely of natural amino acids; therefore, it is easily degraded by a variety of proteases, resulting in poor stability and a short half-life. In the present study, we used a fatty acid modification strategy to improve the stability of Figainin 1. Among the 8 peptides synthesized, A-10 showed the strongest antiproliferative activity against K562 cells and the other four tumor cell lines, and its stability against serum and proteinase K was improved compared with F1. We found that A-10 works through two mechanisms, cell membrane destruction and apoptosis, and can arrest the cell cycle in the G0/G1 phase. Moreover, A-10 exhibited self-assembly behavior. Overall, it is necessary to select a fatty acid with a suitable length for modification to improve the stability and antiproliferative activity of antimicrobial peptides. This study provides a good reference for the development of antimicrobial peptides as effective anticancer compounds.
源自两栖动物皮肤分泌物的抗菌肽因其独特的细胞膜破坏机制，在肿瘤治疗方面取得了重要进展。Figainin 1（F1）是一种来自青蛙皮肤分泌物的由18个氨基酸组成的抗菌肽。在先前的一项研究中，F1被证明可抑制癌细胞增殖。F1完全由天然氨基酸组成；因此，它很容易被多种蛋白酶降解，导致稳定性差和半衰期短。在本研究中，我们采用脂肪酸修饰策略来提高Figainin 1的稳定性。在合成的8种肽中，A - 10对K562细胞和其他四种肿瘤细胞系表现出最强的抗增殖活性，并且与F1相比，其对血清和蛋白酶K的稳定性有所提高。我们发现A - 10通过细胞膜破坏和细胞凋亡两种机制发挥作用，并可使细胞周期停滞在G0/G1期。此外，A - 10表现出自组装行为。总体而言，有必要选择合适长度的脂肪酸进行修饰，以提高抗菌肽的稳定性和抗增殖活性。本研究为开发有效的抗癌化合物抗菌肽提供了良好的参考。
