title: Permeation of a beta-heptapeptide derivative across phospholipid bilayers.
abstract: Based on a number of experiments it is concluded that the fluorescein labeled beta-heptapeptide fluoresceinyl-NH-CS-(S)-beta(3)hAla-(S)-beta(3)hArg-(R)-beta(3)hLeu-(S)-beta(3)hPhe-(S)-beta(3)hAla-(S)-beta(3)hAla-(S)-beta(3)hLys-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 beta-heptapeptide (S)-beta(3)hAla-(S)-beta(3)hArg-(R)-beta(3)hLeu-(S)-beta(3)hPhe-(S)-beta(3)hAla-(S)-beta(3)hAla-(S)-beta(3)hLys-OH can translocate across phospholipid bilayers is supported by independent measurements using Tb(3+)-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 beta-heptapeptide derivative also permeates across phospholipid bilayers. The possible mechanism of the translocation of the particular beta-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.
authors: Department of Chemical Science and Engineering, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka, Japan.
authors: Toshinori
authors: T
authors: Shimanouchi
authors: Peter
authors: P
authors: Walde
authors: James
authors: J
authors: Gardiner
authors: Yogesh R
authors: YR
authors: Mahajan
authors: Dieter
authors: D
authors: Seebach
authors: Anita
authors: A
authors: Thomae
authors: Stefanie D
authors: SD
authors: Krämer
authors: Matthias
authors: M
authors: Voser
authors: Ryoichi
authors: R
authors: Kuboi
mesh_terms: D001692:Biological Transport; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D009842:Oligopeptides / Q000493:pharmacokinetics*; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D009842:Oligopeptides; D010743:Phospholipids