Abstract
There is considerable attention directed at chemically modifying nucleic acids with robust functional groups in order to alter their properties. Since the breakthrough of copper-assisted azide-alkyne cycloadditions (CuAAC), there have been several reports describing the synthesis and properties of novel triazole-modified nucleic acid derivatives for potential downstream DNA- and RNA-based applications. This review will focus on highlighting representative novel nucleic acid molecular structures that have been synthesized via the “click” azide-alkyne cycloaddition. Many of these derivatives show compatibility for various applications that involve enzymatic transformation, nucleic acid hybridization, molecular tagging and purification, and gene silencing. The details of these applications are discussed. In conclusion, the future of nucleic acid analogues functionalized with triazoles is promising.
Highlights
Since its discovery by Meldal and Sharpless in 2001 [1], the Cu(I)-catalyzed adaptation of Huisgen’s 1,3-dipolar [3 + 2] azide-alkyne (CuAAC) cycloaddition has earned the title of “click” reaction, but has nearly become synonomous with the term due its speed, versatility, simplicityMolecules 2012, 17 and its broad applications [2,3,4,5]
Current examples of antiviral nucleic acid-based derivatives which inspire the continued implementation of the CuAAC in developing prospective therapies include the discovery of ribavirin [25,56], a successful 1,2,4-triazole-based antiviral nucleoside analogue, and the potent anti-HIV agent known as azide unit (AZT) (3′-azido-3′-deoxythymidine) [57]
The Winssinger group reported the substitution of an amide linkage in peptide nucleic acid (PNA), a successful oligonucleoside mimic made of repeating aminoethyl-glycine units [135], with a triazole linker [136]
Summary
Since its discovery by Meldal and Sharpless in 2001 [1], the Cu(I)-catalyzed adaptation of Huisgen’s 1,3-dipolar [3 + 2] azide-alkyne (CuAAC) cycloaddition has earned the title of “click” reaction, but has nearly become synonomous with the term due its speed, versatility, simplicity. Chemical modification can be used to append novel functionalities on the nucleic acid molecule for other downstream biological applications Such applications include, but are not limited to the field of molecular diagnostics which encompasses the synthesis of DNA microarrays [10,11,12], molecular probes [13,14], antisense oligonucleotides (ASOs) [15,16], and short-interfering RNAs (siRNAs) [17,18,19]. Some other examples of emerging biologically active nucleic acid derivatives include synthetic ribozymes [26], unique aptamers [27,28], and triplex forming oligonucleotides (TFOs) [29] Due to their structure, there are three main areas within nucleic acids which are commonly altered through chemical modification: the ribose sugar, the nitrogenous base, and the phosphodiester internucleotide linkage. The literature chosen for this review succeeds what was extensively covered by Amblard and colleagues in 2009 [2] and serves to compliment the review by El-Sagheer and Brown in 2010 [8] with current and novel triazole-modified ribo- and 2′-deoxyribonucleic acid compounds
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