Chemical evidence for transbilayer movement of molecular umbrellas

Journal of the American Chemical Society

Volumn 121, Issue 25, 1999, Pages 5860-5864

  Shawaphun, Sarinya ^a   Janout, Vaclav ^a   Regen, Steven L ^a  

^a LEHIGH UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 OLEOYL 1 PALMITOYLPHOSPHATIDYLCHOLINE; 2 PYRIDINETHIOL DERIVATIVE;

ARTICLE; BILAYER MEMBRANE; DRUG SYNTHESIS; HYDROPHILICITY; HYDROPHOBICITY; LIPID BILAYER; MEMBRANE VESICLE; PARTITION COEFFICIENT; PASSIVE TRANSPORT; REACTION ANALYSIS;

EID: 0033618119     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9904641     Document Type: Article

References (24)

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20. Vesicles derived from POPG, which contained 1.3 mM GSH within their aqueous interior, showed negligible peptide release after 24 h. The half-life for permeation of GSH across the dialysis membrane is ca. 2 h, in the absence and in the presence of vesicles containing a thioether analogue of 2.
21. Very poor water solubility of 1 and 2 prevented their external addition to vesicles containing entrapped GSH.
22. Examination of 1 and 2 by CPK models indicates a maximum depth of penetration of the disulfide moiety in an exposed conformation (sterols lying flat at the water/membrane surface) of ca. 16 Å. For a fully exposed conformation (where the hydrophobic side of each sterol faces the alkyl chains of a neighboring phospholipid), the maximum depth of penetration is ca. 30 Å. Thus, incorporation of these umbrellas into a unilamellar vesicle having a bilayer thickness that exceeds 30 A should limit their accessibility toward an externally added, membrane-impermeable reagent to only those disulfide moieties that are located in the outer monolayer leaflet. Since POPG membranes have a bilayer thickness of ca. 37 Å (Lehtonen, J. Y. A.; Kinnunen, P. K. J. Biophys. J. 1997, 72, 1247), the observation of total release of 2-MP provides compelling evidence for transbilayer movement.
23. Vesicles that were formed in the presence of 1 mol % of a thioether analogue of 2 (prepared by condensing 4 with acryloyl chloride, followed by conjugate addition of 2-mercaptopyridine) plus 1.3 mM GSH, followed by gel filtration, resulted in entrapment of the peptide without signficant efflux after 24 h. These results indicate that such tetra-walled umbrellas do not disrupt the integrity of POPG bilayers.
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