Synthesis, penetrability and intracellular targeting of fluorescein-tagged peptoids and peptide-peptoid hybrids

Asier Unciti-Broceta, Franziska Diezmann, Chiung Ying Ou-Yang, Mario Antonio Fara, Mark Bradley

Research output: Contribution to journalArticlepeer-review

Abstract

The search for novel, generally applicable and highly efficient delivery tools is a major activity in the biotechnology arena. Using highly optimized microwave based solid-phase chemistry a series of fluorescein-labelled cationic peptoid conjugates were synthesized within 24 h and cellular uptake into HeLa, L929 and K562 cells examined via flow cytometry. As expected, analysis revealed that longer oligomers achieved greater cellular penetration (7e (9 mer) > 7d (7 mer) > 7c (5 mer) > 7b (3 mer) > 7a (1 mer)) with the nonamer 7e proving to be a remarkable vehicle for all the cell lines, showing excellent penetrability into K562 and L929 cells and extraordinary cell delivery into HeLa cells. Confocal microscopy showed that the hybrid peptoid-nuclear localizing sequence (PKKKRKV from the simian virus 40 large T antigen) resulted in very high levels of nuclei delivery after 3 h, opening up a range of applications such as nuclei staining of living cells with non-DNA-intercalating fluorescent probes. (C) 2008 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)959-966
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number3
DOIs
Publication statusPublished - 1 Feb 2009

Keywords

  • Peptidomimetics
  • Cell-penetrating peptoids
  • Lysine-like peptoids
  • Solid-phase synthesis
  • Peptide-peptoid hybrids
  • Cellular trafficking
  • Endocytosis
  • Nuclear targeting
  • MOLECULAR TRANSPORTERS
  • CELLULAR UPTAKE
  • DRUG DISCOVERY
  • TAT PROTEIN
  • DELIVERY
  • CELLS
  • TRANSLOCATION
  • DESIGN
  • RECOGNITION
  • CONJUGATION

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