Hydrophobic and Polarized Aromatic Residues Promote Internalization of Arg-Rich Cell-Penetrating Peptides through Ionpair-π Interactions.

ABSTRACT: Cell penetrating peptides (CPPs) are small sequences that can cross cell membranes. Arg and Trp are highly prevalent amino acids in natural and synthetic efficient CPP sequences. In particular, Trp is essential and cannot be substituted by other hydrophobic or aromatic amino acids. The aim of the present study is to decipher the role of Trp in synthetic Arg/Trp CPP sequences. To do so, a small peptide library in which this residue was substituted by other natural or nonnatural amino acids was designed. Internalization of these peptides in cells was evaluated, and it appeared that combining aromaticity and hydrophobicity in the presence of Arg residues leads to enhanced internalization. The study of the interaction of these peptides with model lipid membranes revealed that the modulation of

SUBMITTER: Khemaissa S 

PROVIDER: S-EPMC12284625 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature