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

Autor:	Hailing Chen, Meimiao Zhan, Jianbo Liu, Zhihong Liu, Minhong Shen, Fenfang Yang, Yibin Kang, Feng Yin, Zigang Li
Rok vydání:	2022
Předmět:	Cell Line Tumor Drug Discovery Humans Membrane Proteins Nuclear Proteins RNA-Binding Proteins Molecular Medicine Breast Neoplasms Female Triple Negative Breast Neoplasms Endonucleases Peptides Cell Adhesion Molecules
Zdroj:	Journal of Medicinal Chemistry. 65:12188-12199
ISSN:	1520-4804 0022-2623
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::345a5a4094f16c8106416037333039b3 https://doi.org/10.1021/acs.jmedchem.2c00862 Zobrazit plný text záznamu