Selenomethylene Locked Nucleic Acid Enables Reversible Hybridization in Response to Redox Changes

Abstract

Locking up selenium: A new conformationally restricted nucleic acid with a 2′,4′‐selenomethylene bridge (SeLNA) can be reversibly converted into its oxidized form (SeOLNA), and the hybridization of a modified oligonucleotide was shown to be dependent on the oxidation state. A SeLNA‐modified molecular‐beacon‐type probe (see scheme; F=fluorophore, Q=quencher) can be used as a sensor for changes in the redox environment.

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

“…Nitrogen can also be incorporated at the C3' position in the form of a 3'-amino-2',4'-LNA ( Figure 7D ) monomer which has been shown to stabilize oligonucleotides similarly to unmodified LNA with a nuclease resistance greater than PS-modified oligonucleotides [ 157 ]. Incorporation of selenium at C2' in a thymine-bearing LNA nucleoside ( Figure 7E ) has been demonstrated to have a hybridization ability and a nuclease resistance that are highly reversible in response to redox changes of the selenium atom [ 158 ]. Recent work has also looked at this modification in LNA nucleosides bearing an adenine base [ 159 ], but this nucleoside was found to be highly sensitive to heat, making its incorporation into oligonucleotides challenging.…”

Synthesis and Biophysical Properties of C5-Functionalized LNA (Locked Nucleic Acid)

“…The development of novel conformationally restricted nucleotides is a vibrant area of research. 1 , 2 Efforts are driven by the interesting properties of oligodeoxyribonucleotides (ONs) modified with classic examples of conformationally restricted nucleotides such as homo-DNA, 3 hexitol nucleic acid (HNA), 4 cyclohexane nucleic acid (CeNA), 5 bicyclo DNA, 6 tricyclo DNA, 7 or locked nucleic acid (LNA), 8 , 9 which is also known as bridged nucleic acid (BNA). 10 ONs comprising these building blocks display high affinity toward complementary DNA/RNA often due to reduced entropic binding penalties 11 and are accordingly in high demand for a wide range of nucleic acid targeting applications in molecular biology, biotechnology, and pharmaceutical science.…”

“…Many analogues of LNA have been synthesized with the aim of further improving the binding affinity/specificity, enzymatic stability and pharmokinetic characteristics of LNA. 1 , 2 , 16 The vast majority of these efforts have focused on modifying the oxymethylene bridge spanning the C2′/C4′-positions and/or introducing minor-groove-oriented substituents on the bridge. These structural perturbations have resulted in improved enzymatic stability and altered biodistribution and/or toxicity profiles but have generally not resulted in major improvements in binding affinity and specificity.…”

Synthesis of selenomethylene-locked nucleic acid (SeLNA)-modified oligonucleotides by polymerases

“…6a We have recently prepared a new LNA/BNA analogue with a 'Se' atom at the 2 0 -position called SeLNA (Scheme 1). 7 We envision the development of SeLNA-modified aptamers with the scope to resolve the structure of an aptamer-target complex by X-ray crystallography and also to improve the nuclease resistance. Along this line, the enzymatic recognition of 2 0 -SeMe NTPs by RNA polymerases was recently reported.…”