Thiocarbon-protecting groups for RNA synthesis
AssigneesAgilent Technologies, Inc., The Regents of the University of Colorado Denver
InventorsDouglas J. Dellinger, Agnieszka B. Sierzchala, John Turner, Joel Myerson, Zoltan Kupihar, Fernando Ferreira, Marvin H. Caruthers, Geraldine F. Dellinger
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Abstract
Aspects of the invention include 2′ protected nucleoside monomers that are protected at the 2′ site with thiocarbon protecting groups. Thiocarbon protecting groups of interest include thiocarbonate, thionocarbonate, dithiocarbonate groups, as well as thionocarbamate protecting groups. Aspects of the invention further include nucleic acids that include the protecting groups of the invention, as well as methods of synthesizing nucleic acids using the protecting groups of the invention.
Claims20
A compound having the structure of formula (II):
- wherein:
- BP is a protected or unprotected heterocyclic group having a 3 to 20 membered ring system;
- one of R1 and R2 is a protecting group, and the other of R1 and R2 is a phosphoramidite group;
- W is —NH2, —NH—R4 or —NR4—R5, —NH—O—R4 or —NR4—O—R5, wherein R4 and R5 are independently selected from a hydrocarbyl, a substituted hydrocarbyl, an aryl or a substituted aryl, wherein R4 and R5 are optionally cyclically linked, provided that W is not imidazole.
A method comprising:
- (a) providing a nucleoside residue, wherein said nucleoside residue comprises an unprotected hydroxyl group and a 2′-protected nucleotide monomer, wherein said 2′-protected nucleotide monomer has the structure of formula (II):
- wherein:
- BP is a protected or unprotected heterocyclic group having a 3 to 20 membered ring system;
- one of R1 and R2 is a protecting group, and the other of R1 and R2 is a phosphoramidite group;
- W is —NH2, —NH—R4 or —NR4—R5, —NH—O—R4 or —NR4—O—R5, wherein R4 and R5 are independently selected from a hydrocarbyl, a substituted hydrocarbyl, an aryl or a substituted aryl, wherein R4 and R5 are optionally cyclically linked;
- and
- (b) contacting said nucleoside residue with said 2′-protected nucleotide monomer under conditions sufficient to covalently bond said phosphoramidite group of said 2′-protected nucleotide monomer to said unprotected hydroxyl group of said nucleoside residue and produce an internucleotide bond.
A 2′-O-protected nucleic acid comprising the structure:
- wherein:
- BP is a protected or unprotected heterocyclic group having a 3 to 20 membered ring system;
- Q is a thiocarbon protecting group having one of the following structures:
- —C(═S)—W,
- W is —NH2, —NH—R4 or —NR4—R5, —NH—O—R4 or —NR4—O—R5, wherein R4 and R5 are independently selected from a hydrocarbyl, a substituted hydrocarbyl, an aryl or a substituted aryl, wherein R4 and R5 are optionally cyclically linked;
- R12 is selected from the group consisting of hydrogen, a hydrocarbyl, a substituted hydrocarbyl, an aryl and a substituted aryl;
- and
- m is an integer of at least 1.
Dependencies are inferred from the claim text.