Triazole-Modified Nucleic Acids for the Application in Bioorganic and Medicinal Chemistry

Abstract

This review covers studies which exploit triazole-modified nucleic acids in the range of chemistry and biology to medicine. The 1,2,3-triazole unit, which is obtained via click chemistry approach, shows valuable and unique properties. For example, it does not occur in nature, constitutes an additional pharmacophore with attractive properties being resistant to hydrolysis and other reactions at physiological pH, exhibits biological activity (i.e., antibacterial, antitumor, and antiviral), and can be considered as a rigid mimetic of amide linkage. Herein, it is presented a whole area of useful artificial compounds, from the clickable monomers and dimers to modified oligonucleotides, in the field of nucleic acids sciences. Such modifications of internucleotide linkages are designed to increase the hybridization binding affinity toward native DNA or RNA, to enhance resistance to nucleases, and to improve ability to penetrate cell membranes. The insertion of an artificial backbone is used for understanding effects of chemically modified oligonucleotides, and their potential usefulness in therapeutic applications. We describe the state-of-the-art knowledge on their implications for synthetic genes and other large modified DNA and RNA constructs including non-coding RNAs.

Chemical Modifications for a Next Generation of Nucleic Acid Aptamers

“…Due to its bioorthogonal nature, CuAAC can be applied to synthesise nucleic acids with extra functional moieties [78] . Firstly synthesised by either phosphoramidite chemistry or primer extension reaction, using 5‐ethynyl‐dU (EdU) as building blocks, nucleic acids are then conjugated to their azido‐moieties with CuAAC [79] . The synthesis of EdU is well defined and thus it is a readily accessible reagent [80] .…”

“…[78] Firstly synthesised by either phosphoramidite chemistry or primer extension reaction, using 5-ethynyl-dU (EdU) as building blocks, nucleic acids are then conjugated to their azido-moieties with CuAAC. [79] The synthesis of EdU is well defined and thus it is a readily accessible reagent. [80] This post-synthetic ligation, however, has low efficiency.…”

New 1,2,3-Triazole-genipin Analogues and Their Anti-Alzheimer’s Activity

“…1,2,3-Triazole is found in abundance in medicinal compounds. 20 , 21 The triazole ring displays bond acceptor properties capable of forming significant interactions with biomolecular targets through H-bonding, π–π stacking, and dipole interactions. These scaffolds are commonly synthesized through Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition between alkynes and azides (CuAAC) by the concept of click.…”

“…1,2,3-Triazole is a five-membered heterocyclic compound containing two carbon and three nitrogen atoms. 1,2,3-Triazole is found in abundance in medicinal compounds. , The triazole ring displays bond acceptor properties capable of forming significant interactions with biomolecular targets through H-bonding, π–π stacking, and dipole interactions. These scaffolds are commonly synthesized through Cu­(I)-catalyzed Huisgen 1,3-dipolar cycloaddition between alkynes and azides (CuAAC) by the concept of click. − Previously, some triazole derivatives were synthesized as potent and highly selective BuChE inhibitors and neuroprotective agents (Figure ).…”

Chemo-enzymatische Synthese lichtaktivierbarer RNA & Synthese lichtregulierbarer Oligonukleotide zur spektroskopischen Strukturaufklärung

“…[25,26] Wird die Phosphodiestereinheit durch eine Triazoleinheit ersetzt, ergibt sich ebenfalls ein neutrales Rückgrat. [27,28] Ein Ersatz durch eine Guanidiniumeinheit resultiert hingegen in einer positiven Ladung des Oligomers. [29,30] Neben der Modifikation der Phosphodiestereinheit ist es auch möglich das Rückgrat noch umfangreicher anzupassen.…”