PMID: 11906273Mar 22, 2002Paper

Molecular umbrella-assisted transport of thiolated AMP and ATP across phospholipid bilayers

Bioconjugate Chemistry
V JanoutSteven L Regen

Abstract

Two molecular umbrella-nucleoside conjugates (1a and 1b) have been synthesized via thiolate-disulfide displacement by adenosine 5'-O-(3-thiomonophosphate) and adenosine 5'-O-(3-thiotriphosphate) on an activated dimer derived from cholic acid, spermidine, and 5,5'-dithiobis-(2-nitrobenzoic acid). Both conjugates readily enter the aqueous compartment of liposomes made from 1-palmitoyl-2-oleyol-sn-glycero-3-phosphocholine (POPC) and release the free nucleoside upon reaction with entrapped glutathione. Approximately 50% of the thiolated form of AMP is released within 20 min at 23 degrees C; 120 min is required for a similar release of the thiolated form of ATP. The facile cleavage of these conjugates by glutathione, together with the fact that mammalian cells contain millimolar concentrations of this tripeptide in their cytoplasm, suggest that such chemistry may be extended to the practical development of prodrugs, e.g., antisense oligonucleotides that can be delivered into cells.

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Citations

Dec 10, 2002·Current Opinion in Chemical Biology·J Middleton Boon, Bradley D Smith
Dec 5, 2008·Bioconjugate Chemistry·Vaclav Janout, Steven L Regen
Aug 2, 2013·Organic & Biomolecular Chemistry·Christine ChhunAndreea R Schmitzer
May 23, 2015·Chemical Reviews·Nathalie BusschaertPhilip A Gale
Jun 25, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Andrzej S SkwareckiMaria J Milewska
Nov 22, 2011·Bioorganicheskaia khimiia·M A MaslovG A Serebrennikova
Sep 14, 2014·Eukaryotic Cell·Karin Komsic-BuchmannBurkhard Becker
Dec 18, 2020·Frontiers in Molecular Biosciences·Alex Bunker, Tomasz Róg
Sep 9, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Juntao LuoX X Zhu
Nov 19, 2009·Bioconjugate Chemistry·Dongtao GeLei Ren
Apr 10, 2003·Journal of the American Chemical Society·Vaclav JanoutSteven L Regen
Sep 24, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Jiawei ZhangDariush Hinderberger
Jun 27, 2021·Angewandte Chemie·Quentin LaurentStefan Matile
Dec 29, 2012·Organic Letters·Vida CastroFernando Albericio
Nov 10, 2005·Journal of the American Chemical Society·Vaclav JanoutSteven L Regen

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