Method for loading solid supports for nucleic acid synthesis

Details Method for loading solid supports for nucleic acid synthesis Method for loading solid supports for nucleic acid synthesis

C - Chemistry, Metallurgy

07

H

C07H 21/00 (2006.01)

Patent

CA 2200552

New methods of loading solid supports for oligonucleotide synthesis are presented. The new methods comprise coupling a succinylated nucleoside to a solid support using diisopropylcarbodiimide (DIC) as an activator and N- hydroxybenzotriazole (HOBT) as an acid catalyst. DIC is substantially cheaper than the currently used activating agent, 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide (DEC). Furthermore, in the preferred embodiment, when it is used in combination with HOBT, coupling is more efficient, requiring less nucleoside to achieve the same loading densities as in the prior art. The loading process is faster than prior art methods and the overall cost savings of about 43 % are realized.

Des nouveaux procédés permettent de charger des supports solides destinés à la synthèse d'oligonucléotides. Ils consistent à coupler un nucléoside succinylaté sur un support solide en utilisant comme activateur du diisopropylcarbodiimide (DIC) et comme catalyseur acide du N-hydroxybenzotriazole (HOBT). Le DIC est nettement moins cher que l'activateur utilisé à l'heure actuelle, le 1-(3-diméthylaminopropyl)-3-éthylcarbodiimide (DEC). De plus, quand on l'utilise dans le mode de réalisation préféré avec HOBT, le couplage est plus efficace et exige une moindre quantité de nucléoside pour atteindre les mêmes densités de charge qu'avec les solutions actuelles. Le processus de charge se révèle plus rapide qu'avec ces solutions et on obtient une économie globale d'environ 43 %.

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