Co-reporter:Asier Unciti-Broceta, Loredana Moggio, Kevin Dhaliwal, Laura Pidgeon, Keith Finlayson, Chris Haslett and Mark Bradley
Journal of Materials Chemistry A 2011 vol. 21(Issue 7) pp:2154-2158
Publication Date(Web):20 Dec 2010
DOI:10.1039/C0JM03241G
The therapeutic use of nucleic acids has long been heralded as a panacea of medicinal opportunity, a vision enhanced by the introduction of RNA interference technology. The Achilles heel of such an approach is the in vivo delivery of the desired nucleic acid into cells, a practice that lacks selectivity, safety and/or efficiency. Herein we report the safe and efficacious in vitro and in vivo delivery of nucleic acids using tripodal biodegradable cationic lipids. Toxicity reduction and transfection potency of these novel amphiphiles were addressed by designing the compounds to undergo complete intracellular degradation thereby enhancing cargo release while minimising toxicity and potential tissue accumulation. Compounds demonstrated high-efficiency in transfecting DNA into cells both in vitro and in vivo with no signs of toxicity, thus potentially offering a safer alternative to viral transfection for gene therapy application.
Co-reporter:Aleksandra Liberska, Annamaria Lilienkampf, Asier Unciti-Broceta and Mark Bradley
Chemical Communications 2011 vol. 47(Issue 48) pp:12774-12776
Publication Date(Web):01 Nov 2011
DOI:10.1039/C1CC15805H
Herein we report a highly-efficient solid-phase strategy for the modular synthesis of 63 double-tailed lipid-peptide conjugates and their application in DNA delivery.
Co-reporter:Asier Unciti-Broceta, María José Pineda-de-las-Infantas, Miguel Ángel Gallo, Antonio Espinosa
Tetrahedron Letters 2010 Volume 51(Issue 17) pp:2262-2264
Publication Date(Web):28 April 2010
DOI:10.1016/j.tetlet.2010.02.109
The synthesis and characterization of five different 9-alkyl-6-amino[1,2,3]triazolo[3,4-c]-5-azaquinoxalines is described. Due to the notable electrophilic character of the C-6 position of the [1,2,4]triazolo[3,4-c]-5-azaquinoxaline tricyclic system, SNAr amination was achieved simply by reacting the corresponding 6-chloro derivative with ammonia-saturated acetonitrile (a non-nucleophilic polar solvent) in a sealed reaction vessel, using microwave-mediated or conventional heating.Due to the notable electrophilic character of the C-6 position of the [1,2,4]triazolo[3,4-c]-5-azaquinoxaline tricyclic system, direct SNAr amination was performed by reacting the corresponding 6-chloro derivative with ammonia-saturated acetonitrile in a sealed reaction vessel, using microwave-mediated or conventional heating.
Co-reporter:Asier Unciti-Broceta Dr.;María J. Pineda de las Infantas ;Miguel A. Gallo ;Antonio Espinosa
Chemistry - A European Journal 2007 Volume 13(Issue 6) pp:
Publication Date(Web):5 DEC 2006
DOI:10.1002/chem.200600282
The first application of the Wolff–Kishner reduction methodology to electron-poor heteroaromatic compounds is reported. Hydrazino-containing heterocycles with hydrazone-type tautomery have been reduced under basic conditions. This novel chemistry was successfully applied to mono-dehalogenate a number of electron-poor heterocycles in a regioselective manner. According to the experimental results, this reductive process is a base-catalyzed reaction that takes only place in the presence of air, probably through an oxygen-assisted mechanism. As consequence of the specific features of this kind of hydrazone/enehydrazine tautomers, the overall outcome of the process is the synthesis of a Shapiro-type reduction product by simply using a milder version of the Huang–Minlon methodology.
Se presenta la primera aplicación de la metodología usada en la reducción de Wolff-Kishner para compuestos heteroaromáticos π-deficientes. Mediante el empleo de medio básico fuerte se ha conseguido la reducción del grupo hidrazino de distintos compuestos heterocíclicos con una característica común: la presencia de un tautómero hidrazona. Este comportamiento nunca antes descrito se ha aplicado satisfactoriamente en la deshalogenación independiente y regioselectiva de distintas posiciones halogenadas de compuestos heterocíclicos π-deficientes. De acuerdo con los datos experimentales presentados, este proceso reductivo se cataliza por medio de bases fuertes y únicamente tiene lugar en sistemas abiertos, a través de un mecanismo en el que probablemente interviene el oxígeno del aire. Debido a las especiales características de esta clase de tautómeros enehidracino/hidrazónicos, el resultado global del proceso es la síntesis del producto que se obtendría a través de la reducción de Shapiro usando, simplemente, una versión más suave de la modificación de Huang-Minlon.
Co-reporter:Asier Unciti-Broceta, Loredana Moggio, Kevin Dhaliwal, Laura Pidgeon, ... Mark Bradley
Drug Discovery Today (December 2010) Volume 15(Issues 23–24) pp:
Publication Date(Web):1 December 2010
DOI:10.1016/j.drudis.2010.09.432
Co-reporter:Asier Unciti-Broceta, Loredana Moggio, Kevin Dhaliwal, Laura Pidgeon, Keith Finlayson, Chris Haslett and Mark Bradley
Journal of Materials Chemistry A 2011 - vol. 21(Issue 7) pp:NaN2158-2158
Publication Date(Web):2010/12/20
DOI:10.1039/C0JM03241G
The therapeutic use of nucleic acids has long been heralded as a panacea of medicinal opportunity, a vision enhanced by the introduction of RNA interference technology. The Achilles heel of such an approach is the in vivo delivery of the desired nucleic acid into cells, a practice that lacks selectivity, safety and/or efficiency. Herein we report the safe and efficacious in vitro and in vivo delivery of nucleic acids using tripodal biodegradable cationic lipids. Toxicity reduction and transfection potency of these novel amphiphiles were addressed by designing the compounds to undergo complete intracellular degradation thereby enhancing cargo release while minimising toxicity and potential tissue accumulation. Compounds demonstrated high-efficiency in transfecting DNA into cells both in vitro and in vivo with no signs of toxicity, thus potentially offering a safer alternative to viral transfection for gene therapy application.
Co-reporter:Aleksandra Liberska, Annamaria Lilienkampf, Asier Unciti-Broceta and Mark Bradley
Chemical Communications 2011 - vol. 47(Issue 48) pp:NaN12776-12776
Publication Date(Web):2011/11/01
DOI:10.1039/C1CC15805H
Herein we report a highly-efficient solid-phase strategy for the modular synthesis of 63 double-tailed lipid-peptide conjugates and their application in DNA delivery.
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