DNA or RNA Oligonucleotide 2′-Hydrazides for Chemoselective Click-Type Ligation with Carbonyl Compounds

Abstract

An efficient method for the synthesis of DNA or RNA oligonucleotide 2′-hydrazides is described. Fully deprotected oligonucleotides containing a hydrazide group at the 2′-position of a uridine residue were obtained by a novel two-step procedure: periodate cleavage of an oligonucleotide with 1,2-diol group followed by conversion of the aldehyde to hydrazide with an extended linker arm using a homobifunctional reagent succinic dihydrazide and NaBH₃CN. The resulting oligonucleotide 2′-hydrazides were efficiently conjugated by a click-type reaction at acidic pH to aliphatic or aromatic aldehydes with or without NaBH₃CN reduction to afford novel 2′-conjugates.

Keywords:

• Chemoselective ligation
• modified oligonucleotides
• conjugates

ACKNOWLEDGEMENTS

We would like to thank Dr. Vladimir A. Korshun and Dr. Igor A. Prokhorenko for their kind gift of pyrene-1-carbaldehyde and perylene-3-carbaldehyde, and Dr. Evgeniya V. Kazanova for her help with the preparation of this article. This work was supported by the German Research Foundation (DFG) and Russian Foundation for Basic Research (RFBR) Programme “International Research Training Groups” (grants GRK 1384, 11-04-91337), Russian Foundation for Basic Research (grants 09-04-01315, 11-04-12155-ofi-m-2011), and a grant for Leading Scientific Schools (3314.2010.4).