Scaffolding along Nucleic Acid Duplexes Using 2′-Amino-Locked Nucleic Acids

• Published in: Accounts of chemical research 2014-06, Vol.47 (6), p.1768-1777
• Main Authors: Astakhova, I. Kira, Wengel, Jesper
• Format: Article
• Language: English
• Subjects: Biocompatibility; Biomedical materials; Biosensing Techniques; Chemistry Techniques, Synthetic; Deoxyribonucleic acid; DNA - chemistry; DNA Probes - chemistry; DNA Probes - metabolism; Drug Discovery - methods; Fluorescence; Fluorescent Dyes - chemistry; Imaging; Materials science; Molecular Probe Techniques; Nanostructures - chemistry; Nanotechnology - methods; Nucleic Acid Conformation; Nucleic Acid Heteroduplexes - chemistry; Nucleic acids; Oligonucleotides - chemical synthesis; Oligonucleotides - chemistry; Polycyclic Aromatic Hydrocarbons - chemistry; Scaffolds
• ISSN: 0001-4842; 1520-4898
• DOI: 10.1021/ar500014g

Conspectus Incorporation of chemically modified nucleotide scaffolds into nucleic acids to form assemblies rich in function is an innovative area with great promise for nanotechnology and biomedical and material science applications. The intrinsic biorecognition potential of nucleic acids combined with advanced properties of the locked nucleic acids (LNAs) provide opportunities to develop new nanomaterials and devices like sensors, aptamers, and machines. In this Account, we describe recent research on preparation and investigation of the properties of LNA/DNA hybrids containing functionalized 2′-amino-LNA nucleotides. By application of different chemical reactions, modification of 2′-amino-LNA scaffolds can be efficiently performed in high yields and with various tags, postsynthetically or during the automated oligonucleotide synthesis. The choice of a synthetic method for scaffolding along 2′-amino-LNA mainly depends on the chemical nature of the modification, its price, its availability, and applications of the product. One of the most useful applications of the product LNA/DNA scaffolds containing 2′-amino-LNA is to detect complementary DNA and RNA targets. Examples of these applications include sensing of clinically important single-nucleotide polymorphisms (SNPs) and imaging of nucleic acids in vitro, in cell culture, and in vivo. According to our studies, 2′-amino-LNA scaffolds are efficient within diagnostic probes for DNA and RNA targets and as therapeutics, whereas both 2′-amino- and isomeric 2′-α-l-amino-LNA scaffolds have promising properties for stabilization and detection of DNA nanostructures. Attachment of fluorescent groups to the 2′-amino group results in very high fluorescent quantum yields of the duplexes and remarkable sensitivity of the fluorescence signal to target binding. Notably, fluorescent LNA/DNA probes bind nucleic acid targets with advantages of high affinity and specificity. Thus, molecular motion of nanodevices and programmable self-assembly of chemically modified LNA/DNA nanomaterials can be followed by bright fluorescence signaling from the functionalized LNA units. Another appealing aspect of the amino-LNA scaffolds is specific targeting of nucleic acids and proteins for therapeutic applications. 2′-Amino-LNA/DNA conjugates containing peptide and polyaromatic hydrocarbon (PAH) groups are promising in this context as well as for advanced imaging and diagnostic purposes in vivo. For imaging applications, photostability of