Reagents for oligonucleotide cleavage and deprotection

C - Chemistry – Metallurgy – 07 – H

Patent

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C07H 21/00 (2006.01) C07H 19/00 (2006.01) C07H 21/02 (2006.01) C07H 21/04 (2006.01)

Patent

CA 2468425

The present invention provides a process for the removal of protecting groups, i.e. deprotection, from chemically synthesized oligonucleotides. In one embodiment, the invention provides reagents suitable for use in such a process, and kits incorporating such reagents in a convenient, ready-to-use format. By use of the process and reagents of the invention, side-reactions leading to certain impurities that contaminate the synthesized oligonucleotides can be minimized. Methods and reagents are provided for deprotection of an oligonucleotide by reacting a protected oligonucleotide with a deprotection reagent wherein the deprotection reagent comprises an active methylene compound and an amine reagent. The active methylene compound has the structure (a) where substituent EWG is an electron-withdrawing group and R is hydrogen, C1-C12 alkyl, C6-C20 aryl, heterocycle or an electron- withdrawing group.

L'invention porte sur un procédé de retrait de groupes protecteurs, par exemple de déprotection oligonucléotides de synthèse, sur des réactifs utilisables dans un tel procédé, et sur des kits comportant de tels réactifs sous une forme pratique et facile à utiliser. Le procédé et les réactifs de l'invention, permettent de réduire les réactions secondaires produisant certaines impuretés contaminant les oligonucléotides de synthèse. Les procédés et réactifs de déprotection d'oligonucléotides consistent à faire réagir un oligonucléotide protégé avec un agent de déprotection comprenant un composé actif de méthylène et un réactif d'amine. Le composé actif de méthylène présente la structure (a) dans laquelle le substituant d'EWG est un groupe d'extraction d'électrons, et R est H, C¿1?-C¿12? alkyle, C¿6?-C¿20? aryle, un hétérocycle ou un groupe d'extraction d'électrons.

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