Tuning Electrostatic and Hydrophobic Surfaces of Aromatic Rings to Enhance Membrane Association and Cell Uptake of Peptides.
Angew Chem Int Ed Engl
; 61(29): e202203995, 2022 07 18.
Article
em En
| MEDLINE
| ID: mdl-35523729
ABSTRACT
Aromatic groups are key mediators of protein-membrane association at cell surfaces, contributing to hydrophobic effects and π-membrane interactions. Here we show electrostatic and hydrophobic influences of aromatic ring substituents on membrane affinity and cell uptake of helical, cyclic and cell penetrating peptides. Hydrophobicity is important, but subtle changes in electrostatic surface potential, dipoles and polarizability also enhance association with phospholipid membranes and cell uptake. A combination of fluorine and sulfur substituents on an aromatic ring induces microdipoles that enhance cell uptake of 12-residue peptide inhibitors of p53-HDM2 interaction and of cell-penetrating cyclic peptides. These aromatic motifs can be readily inserted into peptide sidechains to enhance their cell uptake.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Peptídeos Penetradores de Células
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article