<i>P</i>-Sulfonatocalix[4]arene turns peptide aggregates into an efficient cell-penetrating peptide.

ABSTRACT: A novel cell-penetrating peptide (CPP) called FAM-Y₄R₄, with FAM as a fluorescent probe, was developed. Initially, we aimed to use Y₄ as a supramolecular host for water-insoluble drugs, with R₄ driving the complex into cells. However, an unexpected hurdle was discovered; the peptide self-assembled into amorphous aggregates, rendering it ineffective for our intended purpose. Molecular dynamics simulations revealed that intermolecular cation-π interactions between arginine and tyrosine caused this aggregation. By decorating the R₄ sidechains with p-sulfonatocalix[4]arene (CX4), we successfully dissolved most of the aggregates, significantly improved the peptide's solubility and enhanced the cell uptake with MCF7 and

SUBMITTER: Heydari M 

PROVIDER: S-EPMC11474258 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature