Size‐Dependent Cellular Uptake of RGD Peptides

• Published in: Chembiochem : a European journal of chemical biology 2020-02, Vol.21 (4), p.496-499
• Main Authors: Kemker, Isabell, Feiner, Rebecca C., Müller, Kristian M., Sewald, Norbert
• Format: Article
• Language: English
• Subjects: Biological Transport; Cell Line, Tumor; Communication; Communications; Coupling (molecular); Cross coupling; Endocytosis; Flow Cytometry; Fluorescent Dyes; Fluorescent indicators; halogenated tryptophan; Humans; Integrin alphaVbeta3 - metabolism; Internalization; Lysine; Oligopeptides - metabolism; Peptides; poly(ethylene glycol); Polyethylene glycol; Polyethylene Glycols; RGD peptides; selective uptake
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201900512

Monomeric RGD peptides show unspecific fluid‐phase uptake in cells, whereas multimeric RGD peptides are thought to be internalized by integrin‐mediated endocytosis. However, a potential correlation between uptake mechanism and molecular mass has been neglected so far. A dual derivatization of peptide c(RGDw(7Br)K) was performed to investigate this. A fluorescent probe was installed by chemoselective Suzuki–Miyaura cross‐coupling of the 7‐bromotryptophan and a poly(ethylene glycol) (PEG) linker was attached to the lysine residue. Flow cytometry and live cell imaging confirmed unspecific uptake of the small, non‐PEGylated peptide, whereas the PEG5000 peptide conjugate unveiled a selective internalization by M21 cells overexpressing αvβ3 and no uptake in αv‐deficient M21L cells. Mass matters: Uptake of RGD peptides depends on the molecular size as investigated with a large PEGylated and a small non‐PEGylated peptide. Only the PEGylated peptide is found in αvβ3‐overexpressing cells, while the small peptide also enters αv‐negative cells.