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.
J Med Chem. 2022 Sep 22;65(18):12188-12199. doi: 10.1021/acs.jmedchem.2c00862. Epub 2022 Aug 31.
Blocking the interaction of MTDH/SND1 complex is an attractive strategy for cancer therapeutics. In this work, we designed and obtained a novel class of potent stabilized peptide inhibitors derived from MTDH sequence to disrupt MTDH/SND1 interaction. Through structure-based optimization and biological evaluation, stabilized peptides were obtained with tight binding affinity, improved cell penetration, and antitumor effects in the triple-negative breast cancer (TNBC) cells without nonspecific toxicity. To date, our study was the first report to demonstrate that stabilized peptides truncated from MTDH could serve as promising candidates to disrupt the MTDH/SND1 interaction for potential breast cancer treatment.
阻断 MTDH/SND1 复合物的相互作用是癌症治疗的一个有吸引力的策略。在这项工作中，我们设计并获得了一类新型有效的稳定化肽抑制剂，这些抑制剂来源于 MTDH 序列，可破坏 MTDH/SND1 相互作用。通过基于结构的优化和生物学评价，获得了具有紧密结合亲和力、改善细胞穿透性和在三阴性乳腺癌（TNBC）细胞中抗肿瘤作用的稳定化肽，而没有非特异性毒性。迄今为止，我们的研究首次表明，从 MTDH 截断的稳定化肽可以作为有前途的候选物，用于破坏 MTDH/SND1 相互作用，以用于潜在的乳腺癌治疗。
