我们已经证明，从鲎源性 LALF32-51 区域通过丙氨酸扫描设计出的肽L-2 是一种潜在的抗癌治疗候选药物，其细胞穿透能力是一项相关的有用特性。通过对 L-2 一级结构的修饰，开发出了第二代肽（CIGB-552）。然而，其细胞毒性作用的分子机制仍部分未知。在本研究中，我们发现 CIGB-552 可提高 COMMD1 的水平，COMMD1 是一种参与铜稳态、钠转运和 NF-κB 信号通路的蛋白质。我们还发现 CIGB-552 可诱导 RelA 的泛素化，并抑制由 NF-κB 调节的抗凋亡活性，而 COMMD1 的敲低则会阻断这种效应。此外，我们发现 CIGB-552 可降低肿瘤细胞的抗氧化能力，并诱导蛋白质和脂质的过氧化。总之，本研究为肽 CIGB-552 的作用机制提供了新的见解，这可能对未来的抗癌治疗设计具有重要意义。

We have demonstrated that the peptide L-2 designed from an alanine scanning of the Limulus-derived LALF32-51 region is a potential candidate for the anticancer therapy and its cell-penetrating capacity is an associated useful property. By the modification in the primary structure of L-2, a second-generation peptide (CIGB-552) was developed. However, the molecular mechanism underlying its cytotoxic activity remains partially unknown. In this study, it was shown that CIGB-552 increases the levels of COMMD1, a protein involved in copper homeostasis, sodium transport, and the NF-κB signaling pathway. We found that CIGB-552 induces ubiquitination of RelA and inhibits the antiapoptotic activity regulated by NF-κB, whereas the knockdown of COMMD1 blocks this effect. We also found that CIGB-552 decreases the antioxidant capacity and induces the peroxidation of proteins and lipids in the tumor cells. Altogether, this study provides new insights into the mechanism of action of the peptide CIGB-552, which could be relevant in the design of future anticancer therapies.

单字母 Ac-HARIKpTFRRlKWKYKGKFW-OH
多字母 Ac-His-Ala-Arg-Ile-Lys-DPro-Thr-Phe-Arg-Arg-DLeu-Lys-Trp-Lys-Tyr-Lys-Gly-Lys-Phe-Trp-OH
氨基酸个数 20
分子式 C131H198O24N38
平均分子量(MW) 2689.21
精确分子量(Exact Mass)(MW) 2687.54
等电点(PI) -
pH=7.0时的净电荷数 9.23
GRAVY -1.3
亲水残基比例 -
消光系数 12490
溶解建议 亲水

参考文献：
Lugo JM, Tafalla C, Oliva A, et al. Evidence for antimicrobial and anticancer activity of pituitary adenylate cyclase-activating polypeptide (PACAP) from North African catfish (Clarias gariepinus): Its potential use as novel therapeutic agent in fish and humans. Fish Shellfish Immunol. 2019;86:559-570. doi:10.1016/j.fsi.2018.11.056
Fernu00e1ndez Massu00f3 JR, Oliva Argu00fcelles B, Tejeda Y, et al. The Antitumor Peptide CIGB-552 Increases COMMD1 and Inhibits Growth of Human Lung Cancer Cells. J Amino Acids. 2013;2013:251398. doi:10.1155/2013/251398