Structure-Based Design, Optimization, and Evaluation of Potent Stabilized Peptide Inhibitors Disrupting MTDH and SND1
Hailing Chen1, Meimiao Zhan1, Jianbo Liu2
1State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Abstract:
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.
