Chen Hailing, Zhan Meimiao, Zhang Yaping, Liu Jianbo, Wang Rui, An Yuhao, Gao Zhanxia, Jiang Leying, Xing Yun, Kang Yibin, Li Zigang, Yin Feng
State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518118, China.
JACS Au. 2023 Dec 8;4(1):139-149. doi: 10.1021/jacsau.3c00573. eCollection 2024 Jan 22.
Triple-negative breast cancer is one of the most prevalent malignant cancers worldwide. Disrupting the MTDH-SND1 protein-protein interaction has recently been shown to be a promising strategy for breast cancer therapy. In this work, a novel potent stabilized peptide with a stronger binding affinity was obtained through rational structure-based optimization. Furthermore, a sulfonium-based peptide delivery system was established to improve the cell penetration and antitumor effects of stabilized peptides in metastatic breast cancer. Our study further broadens the in vivo applications of the stabilized peptides for blocking MTDH-SND1 interaction and provides promising opportunities for breast cancer therapy.
三阴性乳腺癌是全球最常见的恶性肿瘤之一。最近研究表明，破坏MTDH-SND1蛋白-蛋白相互作用是一种很有前景的乳腺癌治疗策略。在这项研究中，通过基于结构的合理优化，获得了一种具有更强结合亲和力的新型强效稳定肽。此外，还建立了一种基于锍的肽递送系统，以提高稳定肽在转移性乳腺癌中的细胞穿透能力和抗肿瘤效果。我们的研究进一步拓宽了稳定肽在体内阻断MTDH-SND1相互作用的应用，并为乳腺癌治疗提供了有希望的机会。
