Molecular umbrella-assisted transport of glutathione across a phospholipid membrane.
J Am Chem Soc
; 123(23): 5401-6, 2001 Jun 13.
Article
in En
| MEDLINE
| ID: mdl-11389618
ABSTRACT
A di-walled molecular umbrella (1a) has been synthesized by acylation of the terminal amino groups of spermidine with cholic acid, followed by condensation with bis(3-O-[N-1,2,3-benzotriazin-4(3H)-one]yl)-5,5'-dithiobis-2-nitrobenzoate (BDTNB), and displacement with glutathione (gamma-Glu-Cys-Gly, GSH). Replacement of the sterol hydroxyls with sulfate groups, prior to displacement with GSH, afforded a hexasulfate analogue 1b. Both conjugates have been found to enter large unilamellar vesicles (200 nm diameter, extrusion) of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and to react with entrapped GSH to form oxidized glutathione (GSSG). Evidence for vesicular entry has come from the formation of oxidized glutathione (GSSG) within the interior of the vesicle, the appearance of the thiol form of the umbrella (USH), and the absence of release of GSH into the external aqueous phase. Results that have been obtained from monolayer experiments, together with the fact that the heavily sulfated conjugate is able to cross the phospholipid bilayer, have yielded strong inferential evidence for an "umbrella-like" action of these molecules as they cross the lipid bilayer.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glutathione
/
Lipid Bilayers
Language:
En
Journal:
J Am Chem Soc
Year:
2001
Document type:
Article
Affiliation country:
United States