Permeation of a β-heptapeptide derivative across phospholipid bilayers

Toshinori Shimanouchi, Peter Walde, James Gardiner, Yogesh R. Mahajan, Dieter Seebach, Anita Thomae, Stefanie D. Krämer, Matthias Voser, Ryoichi Kuboi

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


Based on a number of experiments it is concluded that the fluorescein labeled β-heptapeptide fluoresceinyl-NH-CS-(S)-β3hAla-(S)-β3hArg-(R)-β3hLeu-(S)-β3hPhe-(S)-β3hAla-(S)-β3hAla-(S)-β3hLys-OH translocates across lipid vesicle bilayers formed from DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine). The conclusion is based on the following observations: (i) addition of the peptide to the vicinity of micrometer-sized giant vesicles leads to an accumulation of the peptide inside the vesicles; (ii) if the peptide is injected inside individual giant vesicles, it is released from the vesicles in a time dependent manner; (iii) if the peptide is encapsulated within sub-micrometer-sized large unilamellar vesicles, it is released from the vesicles as a function of time; (iv) if the peptide is submitted to immobilized liposome chromatography, the peptide is retained by the immobilized DOPC vesicles. Furthermore, the addition of the peptide to calcein-containing DOPC vesicles does not lead to significant calcein leakage and vesicle fusion is not observed. The finding that derivatives of the β-heptapeptide (S)-β3hAla-(S)-β3hArg-(R)-β3hLeu-(S)-β3hPhe-(S)-β3hAla-(S)-β3hAla-(S)-β3hLys-OH can translocate across phospholipid bilayers is supported by independent measurements using Tb3+-containing large unilamellar vesicles prepared from egg phosphatidylcholine and wheat germ phosphatidylinositol (molar ratio of 9:1) and a corresponding peptide that is labeled with dipicolinic acid instead of fluorescein. The experiments show that this dipicolinic acid labeled β-heptapeptide derivative also permeates across phospholipid bilayers. The possible mechanism of the translocation of the particular β-heptapeptide derivatives across the membrane of phospholipid vesicles is discussed within the frame of the current understanding of the permeation of certain oligopeptides across simple phospholipid bilayers.

Original languageEnglish
Pages (from-to)2726-2736
Number of pages11
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number11
Publication statusPublished - Nov 2007
Externally publishedYes


  • Cell penetrating peptide
  • Liposome
  • Permeability
  • Vesicle

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology


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