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

TitleStructure-Based Design, Optimization, and Evaluation of Potent Stabilized Peptide Inhibitors Disrupting MTDH and SND1 Interaction.
Publication TypeJournal Article
Year of Publication2022
AuthorsChen, H, Zhan, M, Liu, J, Liu, Z, Shen, M, Yang, F, Kang, Y, Yin, F, Li, Z
JournalJ Med Chem
Volume65
Issue18
Pagination12188-12199
Date Published2022 Sep 22
ISSN1520-4804
KeywordsBreast Neoplasms, Cell Adhesion Molecules, Cell Line, Tumor, Endonucleases, Female, Humans, Membrane Proteins, Nuclear Proteins, Peptides, RNA-Binding Proteins, Triple Negative Breast Neoplasms
Abstract

<p>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.</p>

DOI10.1021/acs.jmedchem.2c00862
Alternate JournalJ Med Chem
PubMed ID36044768