Unnatural Peptide Assemblies Rapidly Deplete Cholesterol and Potently Inhibit Cancer Cells.
J Am Chem Soc
; 146(19): 12901-12906, 2024 May 15.
Article
em En
| MEDLINE
| ID: mdl-38701349
ABSTRACT
Cholesterol-rich membranes play a pivotal role in cancer initiation and progression, necessitating innovative approaches to target these membranes for cancer inhibition. Here we report the first case of unnatural peptide (1) assemblies capable of depleting cholesterol and inhibiting cancer cells. Peptide 1 self-assembles into micelles and is rapidly taken up by cancer cells, especially when combined with an acute cholesterol-depleting agent (MßCD). Click chemistry has confirmed that 1 depletes cell membrane cholesterol. It localizes in membrane-rich organelles, including the endoplasmic reticulum, Golgi apparatus, and lysosomes. Furthermore, 1 potently inhibits malignant cancer cells, working synergistically with cholesterol-lowering agents. Control experiments have confirmed that C-terminal capping and unnatural amino acid residues (i.e., BiP) are essential for both cholesterol depletion and potent cancer cell inhibition. This work highlights unnatural peptide assemblies as a promising platform for targeting the cell membrane in controlling cell fates.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Colesterol
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article