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

Research output: Contribution to journalArticle

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

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.

    Research areas

  • 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

ID: 1481058