Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Tiantanxili, Dongcheng District, Beijing, China.
Shen Yang Tonglian Group Co., Ltd., Dadong District, Shen Yang, China.
ChemMedChem. 2021 Nov 19;16(22):3477-3483. doi: 10.1002/cmdc.202100323. Epub 2021 Sep 6.
The peroxiredoxin 5 (PRDX5) is a member of peroxiredoxins with antitumor activity. However, as a recombinant protein, PRDX5 is restricted in clinic due to high cost and keeping high dose in medication. The alternative way is to explore the antitumor active fragments of PRDX5 for potential of peptide drugs. According to the sequence, crystal structure and enzyme function of PRDX5, seven peptides were designed and named as IMB-P1∼7. The peptide IMB-P1 (AFTPGCSKTHLPGFVEQAEAL) containing critical residue C47 exhibited antitumor activity similar to PRDX5 in vivo. Transcriptome analysis showed peptide IMB-P1 could make influence on expression of multiple genes involved in tumorigenesis and deterioration. Besides, an important discovery is the down-regulation of oxidation-related genes. In CT26 cells, IMB-P1 carried similar antitumor activity with increasing ROS level to intact PRDX5. The results demonstrated that peptide IMB-P1 with easier synthesis from PRDX5 may serve as a promising antitumor candidate.
过氧化物酶 5(PRDX5)是具有抗肿瘤活性的过氧化物酶家族的一员。然而,作为一种重组蛋白,由于成本高和药物剂量高,PRDX5 在临床上受到限制。另一种方法是探索 PRDX5 的抗肿瘤活性片段,以开发潜在的肽类药物。根据 PRDX5 的序列、晶体结构和酶功能,设计了 7 条肽段并命名为 IMB-P1∼7。含有关键残基 C47 的肽段 IMB-P1(AFTPGCSKTHLPGFVEQAEAL)在体内表现出与 PRDX5 相似的抗肿瘤活性。转录组分析表明,肽段 IMB-P1 可能会影响多个与肿瘤发生和恶化相关的基因的表达。此外,一个重要的发现是氧化相关基因的下调。在 CT26 细胞中,IMB-P1 表现出与完整 PRDX5 相似的抗肿瘤活性,同时增加了 ROS 水平。结果表明,肽段 IMB-P1 可能作为一种有前途的抗肿瘤候选药物,其合成比 PRDX5 更容易。