Abstract

Nucleic acids are able to adopt a plethora of structures, many of which are of interest in therapeutics, bio- or nanotechnology. However, structural and biochemical stability is a major concern which has been addressed by incorporating a range of modifications and nucleoside derivatives. This review summarizes the use of locked nucleic acid (LNA) and un-locked nucleic acid (UNA) monomers in functional nucleic acids such as aptamers, ribozymes, and DNAzymes.

Highlights

  • Ribozymes, DNAzymes, and aptamers, collectively referred to as ‘functional nucleic acids’, are RNA or DNA structures with sequence-specific folds

  • Aptamers are nucleic acid oligonucleotides, whose sequence allows them to fold into defined tertiary structures that act as ligands and bind their corresponding target molecule with specificity and affinity rivalling that of antibodies

  • The same goes for other locked nucleic acid (LNA) derivatives such as amino-LNA [124], which has not been covered by this review

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Summary

Introduction

DNAzymes, and aptamers, collectively referred to as ‘functional nucleic acids’, are RNA or DNA structures with sequence-specific folds. These functional nucleic acids achieve their tertiary folds and activity through a combination of different molecular interactions and motifs: Hydrogen bonds, hydrophobic interactions, van der Waals forces, canonical and non-canonical base pairs, base stacking, coaxial stacking, tetraloops, G-quadruplexes, and metal ion coordination [1,2]. Non-natural nucleosides may offer improved half-life in vivo, better structural stability, or novel interacting groups. 2’-modified ribonucleoside analogues have attracted interest, as modification to this position on the ribose often confers improved nuclease resistance and allows fine-tuning of the helical structure. Molecules 2011, 16 ribonucleoside analogues [3,4,5] in particular have gained interest over the last decade, and the recent advent of the conceptually opposite ‘unlocked’ nucleoside analogues [6,7] have expanded the biochemists’ tool set even further

Locked Nucleic Acids
LNA in Aptamers
LNA in Catalytic Nucleic Acids
Properties
UNA in Aptamers
De Novo Selection of Modified Nucleic Acid Structures
Conclusions

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