AUTHOR=Yang Jian , Liao Xiufei , Hu Damin , Mo Jinqiu , Gao Xiurong , Liao Hongli 

TITLE=Study on the design, synthesis, and activity of anti-tumor staple peptides targeting MDM2/MDMX

JOURNAL=Frontiers in Chemistry

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1403473

DOI=10.3389/fchem.2024.1403473

ISSN=2296-2646

ABSTRACT=<p>Staple peptides, which have a significantly enhanced pharmacological profile, are promising therapeutic molecules due to their remarkable resistance to proteolysis and cell-penetrating properties. In this study, we designed and synthesized a series of PMI-M3-based dual-targeting MDM2/MDMX staple peptides and compared them with straight-chain peptides. The staple peptide SM3-4 screened in the study induced apoptosis of tumor cells <italic>in vitro</italic> at low μM concentrations, and the helix was significantly increased. Studies have shown that the enhancement of staple activity is related to the increase in helicity, and SM3-4 provides an effective research basis for dual-targeted anti-tumor staple peptides.</p>