2. Academic Validation
  3. Structure-Based Design, Optimization, and Evaluation of Potent Stabilized Peptide Inhibitors Disrupting MTDH and SND1 Interaction

Structure-Based Design, Optimization, and Evaluation of Potent Stabilized Peptide Inhibitors Disrupting MTDH and SND1 Interaction

  • J Med Chem. 2022 Sep 22;65(18):12188-12199. doi: 10.1021/acs.jmedchem.2c00862.
Hailing Chen 1,  Meimiao Zhan 1,  Jianbo Liu 2,  Zhihong Liu 1,  Minhong Shen 3,  Fenfang Yang 1,  Yibin Kang 4,  Feng Yin 2,  Zigang Li 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
  • 2 Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518118, China.
  • 3 Ludwig Institute for Cancer Research Princeton Branch, Princeton, New Jersey 08544, United States.
  • 4 Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, United States.
PMID: 36044768 DOI: 10.1021/acs.jmedchem.2c00862
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.

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