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

Hailing Chen, Meimiao Zhan, Jianbo Liu, Zhihong Liu, Minhong Shen, Fenfang Yang, Yibin Kang, Feng Yin, Zigang Li

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)12188-12199
Number of pages12
JournalJournal of Medicinal Chemistry
Volume65
Issue number18
DOIs
StatePublished - Sep 22 2022

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Molecular Medicine

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