Use of carbonyl group addition-elimination reactions for synthesis of nucleic acid conjugates

Timofei S. Zatsepin, Dmitry A. Stetsenko, Michael J. Gait, Tatiana S. Oretskaya

Research output: Contribution to journalReview articlepeer-review

80 Citations (Scopus)

Abstract

This review outlines the synthesis of covalent conjugates of oligonucleotides and their analogues that are obtained by reactions of carbonyl compounds with various nucleophiles such as primary amines, N-alkoxyamines, hydrazines, and hydrazides. The products linked by imino, oxime, hydrazone, or thiazolidine groups are shown to be useful intermediates for a wide range of chemical biology applications. Methods for their preparation, isolation, purification, and analysis are highlighted, and the comparative stabilities of the respective linkages are evaluated. The relative merits of incorporation of a carbonyl group, particularly an aldehyde group, into either the oligonucleotide or the ligand parts are considered. Examples of harnessing of aldehyde-nucleophile coupling for the labeling of nucleic acids are given, as well as their conjugation to various biomolecules (e.g. peptides and small molecule ligands), site-specific cross-linking of oligonucleotides to nucleic acid-binding proteins, assembly of multibranched supramolecular structures, and immobilization on functionalized surfaces. Future perspectives of bioconjugation and complex molecular engineering via carbonyl group addition-elimination reactions in nucleic acids chemistry are discussed.

Original languageEnglish
Pages (from-to)471-489
Number of pages19
JournalBioconjugate Chemistry
Volume16
Issue number3
DOIs
Publication statusPublished - May 2005
Externally publishedYes

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