Method for polynucleotide synthesis

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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C536S025300, C536S025310, C536S025330

Reexamination Certificate

active

07417139

ABSTRACT:
Methods of forming an internucleotide bond are disclosed. Such methods find use in synthesis of polynucleotides. The method involves contacting a functionalized support with a precursor having an exocyclic amine triaryl methyl protecting group under conditions and for a time sufficient to result in internucleotide bond formation. The functionalized support includes a solid support, a triaryl methyl linker group, and a nucleoside moiety having a reactive site hydroxyl, the nucleoside moiety attached to the solid support via the triaryl methyl linker group. In particular embodiments, the precursor has the structure:wherein:O and H represent oxygen and hydrogen, respectivelyR1 is hydrido, hydroxyl, protected hydroxyl, lower alkyl, modified lower alkyl, or alkoxy,one of R2 or R3 is a hydroxyl protecting group; and the other of R2 or R3 is a reactive group capable of reacting with the reactive site hydroxyl,Base is a heterocyclic base having an exocyclic amine group, andTram is the exocyclic amine triaryl methyl protecting group.

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Smith et al., “Studies on Polynucleotides. XIV. Specific Synthesis of the C3′-C′ Internucleotide Linkage. Synthesis of Uridylyl-(3′-5′)-Uridine and Uridylyl-3′-5′)-Adenosine,”J. Amer. Chem. Soc., 84, 430-440 (Feb. 5, 1962).
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