Lipopolythioureas:  A New Non-Cationic System for Gene Transfer

Leblond, Jeanne; Mignet, Nathalie; Largeau, Céline; Spanedda, Maria Vittoria; Séguin, Johanne; Scherman, Daniel; Herscovici, Jean

doi:10.1021/bc060141b

Cited by 33 publications

(40 citation statements)

References 32 publications

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“…As previously reported [18], the lipid 1a is able to compact DNA at a TU/P ratio of 10. A gel retardation experiment showed that the lipid 1b is also able to compact DNA but requires a TU/P ratio of 40 ( Figure 6).…”

Section: -Physico-chemical Properties and Interaction With Dnasupporting

confidence: 83%

“…However, this does not reflect all the mechanisms of interaction between thiourea lipids and DNA as compound 1b which only bears thiourea functions is able to interact with DNA although less efficiently. The compounds from the "lysine" lipopolythiourea family [16][17][18] which are also able to compact DNA do not undergo acidic conditions during their synthesis which implies that DNA compaction does not necessarily need electrostatic interactions. The lysine structure of this family of compounds might induce rigidity in the lipid structure which surely affects the DNA compaction.…”

Section: Discussionmentioning

confidence: 99%

“…Two families showed the best results, one that derives from a serinol compound [18], the other from a lysine moiety [19]. Among these lipids, some showed a blood circulation time twice that of the cationic lipid RPR209120/DOPE [19] and in vitro transfection in the same magnitude.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

“…HCl for the last step of the synthesis) synthesized as previously described [18] was found to be unstable upon storage of the lyophilisate at 4°C. This seemed to be a consequence of the acidity of the last step of the synthesis.…”

Section: -Lipids Synthesismentioning

confidence: 99%

“…Owing to the amphiphilic nature of the compounds the 1 H-NMR spectra were poorly resolved, the major differences being observable in the zone 3 to 4. publication [18] however the signal corresponding to thiourea barely rose above the noise baseline in the case of compound 1a in routine NMR conditions. These preliminary observations confirmed that the differences between the two lipids are due to the thiourea group.…”

mentioning

confidence: 93%

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Iminothiol/thiourea tautomeric equilibrium in thiourea lipids impacts DNA compaction by inducing a cationic nucleation for complex assembly

Breton¹,

Bessodes²,

Bouaziz³

et al. 2009

Biophysical Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 Abstract: Our research on lipidic vectors for transfection led us to develop thiourea lipids able to interact with DNA. Hence, we developed a series of lipopolythioureas based on the strong hydrogen bond donor ability of thiourea. More recently we have reported a branched hydroxylated bis-thiourea derivative with interesting transfecting properties. The last step of the syntheses involved a strong acidic condition, leading to an unstable product upon storage.Therefore we designed a new synthesis in mild acidic conditions. Though they exhibit the same mass, the lipids obtained in the two different conditions differ by their interaction with DNA. We therefore explored the physicochemical properties of these two lipids by different means that we describe in this article. In order to insure easier and reliable 13 C-NMR studies of the thiourea group we have designed the synthesis of the corresponding 13 C-labelled thiourea lipids. We have thus shown that when the lipid was submitted to mildly acidic medium; only the thiourea group was observed; while a thiourea/charged and/or uncharged iminothiol tautomeric equilibrium formed when the last step of the synthesis was submitted to low pH. NMR experiments showed that this tautomeric equilibrium could not form in polar solvents. However, UV experiments on the liposomal form of the lipopolythiourea showed the presence of the tautomers. Lipid/DNA interaction consequently differed according to the acidic treatment applied. Eventually, these results revealed that on this particular thiourea lipid, electrostatic interactions due to cationic thioureas are likely to be responsible for DNA compaction and that this tautomeric form of the thiourea could be stabilised by hydrogen bonds in a supramolecular assembly. Nevertheless, this does not reflect a general thiourea lipid/DNA interaction as other thiourea lipids that are able to compact DNA do not undergo an acidic treatment during the final stage of their synthesis.

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Section: -Physico-chemical Properties and Interaction With Dnasupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Accepted M Manuscriptmentioning

confidence: 99%

Section: -Lipids Synthesismentioning

confidence: 99%

mentioning

confidence: 93%

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Iminothiol/thiourea tautomeric equilibrium in thiourea lipids impacts DNA compaction by inducing a cationic nucleation for complex assembly

Breton¹,

Bessodes²,

Bouaziz³

et al. 2009

Biophysical Chemistry

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How Regenerative Medicine Can Benefit from Nucleic Acids Delivery Nanocarriers?

Borrajo

Vidal

Alonso

et al. 2014

Polymers in Regenerative Medicine

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Polycationic Amphiphilic Cyclodextrins for Gene Delivery: Synthesis and Effect of Structural Modifications on Plasmid DNA Complex Stability, Cytotoxicity, and Gene Expression

Díaz‐Moscoso

Gourriérec

Gómez-Garcı́a

et al. 2009

Chemistry A European J

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A molecular-diversity-oriented approach for the preparation of well-defined polycationic amphiphilic cyclodextrins (paCDs) as gene-delivery systems is reported. The synthetic strategy takes advantage of the differential reactivity of primary versus secondary hydroxyl groups on the CD torus to regioselectively decorate each rim with cationic elements and lipophilic tails, respectively. Both the charge density and the hydrophobic-hydrophilic balance can be finely tuned in a highly symmetrical architecture that is reminiscent of both cationic lipids and cationic polymers, the two most prominent types of nonviral gene vectors. The monodisperse nature of paCDs and the modularity of the synthetic scheme are particularly well suited for structure-activity relationship studies. Gel electrophoresis revealed that paCDs self-assemble in the presence of plasmid DNA (pDNA) to provide homogeneous, stable nanoparticles (CDplexes) of 70-150 nm that fully protect pDNA from the environment. The transfection efficiency of the resulting CDplexes has been investigated in vitro on BNL-CL2 and COS-7 cell lines in the absence and presence of serum and found to be intimately dependent on architectural features. Facial amphiphilicity and the presence of a cluster of cationic and hydrogen-bonding centers for cooperative and reversible complexation of the polyanionic DNA chain is crucial to attain high transgene expression levels with very low toxicity profiles. Further enhancement of gene expression, eventually overcoming that of polyplexes from commercial polyethyleneimine (PEI) polymers (22 kDa), is achieved by building up space-oriented dendritic polycationic constructs.

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Lipopolythioureas: A New Non-Cationic System for Gene Transfer

Cited by 33 publications

References 32 publications

Iminothiol/thiourea tautomeric equilibrium in thiourea lipids impacts DNA compaction by inducing a cationic nucleation for complex assembly

Iminothiol/thiourea tautomeric equilibrium in thiourea lipids impacts DNA compaction by inducing a cationic nucleation for complex assembly

How Regenerative Medicine Can Benefit from Nucleic Acids Delivery Nanocarriers?

Polycationic Amphiphilic Cyclodextrins for Gene Delivery: Synthesis and Effect of Structural Modifications on Plasmid DNA Complex Stability, Cytotoxicity, and Gene Expression

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