The expanding world of DNA and RNA

Abstract

DNA and RNA are remarkable because they can both encode information and possess desired properties, including the ability to bind specific targets or catalyze specific reactions. Nucleotide modifications that do not interfere with enzymatic synthesis are now being used to bestow DNA or RNA with properties that further increase their utility, including phosphate and sugar modifications that increase nuclease resistance, nucleobase modifications that increase the range of activities possible, and even whole nucleobase replacement that results in selective pairing and the creation of unnatural base pairs that increase the information content. These modifications are increasingly being applied both in vitro and in vivo, including in efforts to create semi-synthetic organisms with altered or expanded genetic alphabets.

Photochemical and Photodynamical Properties of Sulfur‐Substituted Nucleic Acid Bases,

“…Thionated nucleoside derivatives analogous to the thiobases have recently been used to expand the genetic alphabet to six bases (147)(148)(149)(150)(151). The base pair consisting of dNaM [2-methoxy-3-(2 0 -deoxy-b-d-erythro-pentofuranosyl)-naphthalene] and d5SICS [2-(2 0 -deoxy-b-d-erythro-pentofuranosyl)-5-methylisoquinolinethione] (Fig.…”

Enzymatic Synthesis, Amplification, and Application of DNA with a Functionalized Backbone

“…Theu tility of DNAf or these applications stems from its precisely controllable sequence composition and base pairing, which enables the polymerase chain reaction (PCR) amplification of specific polymers and/or the control of their assembly into higher order structures;h owever their physicochemical properties are limited to those possessed by the four nucleobases,s ugar, and phosphate.T hus,t ot ake full advantage of the precise sequence composition available with DNA, modifications have been sought that may be introduced to one or more of the triphosphates without interfering with their polymerase recognition. Themost success has been achieved with nucleobase modifications, [11][12][13][14][15][16][17][18] which have been used to develop aptamers with protein-like properties, [19,20] or to introduce sites for the attachment of other moieties by click chemistry. [21][22][23][24][25] However this approach is mostly limited to pyrimidine modifications,and the modified oligonucleotides themselves are not well recognized by polymerases,p reventing their production via PCR-mediated amplification.…”

“…[21][22][23][24][25] However this approach is mostly limited to pyrimidine modifications,and the modified oligonucleotides themselves are not well recognized by polymerases,p reventing their production via PCR-mediated amplification. [11] An alternative approach is to introduce modifications to the sugar moiety.P olymerases are generally less tolerant of sugar modifications,b ut natural or evolved variants capable of the "transcription", "reverse transcription", or even PCRamplification of sugar-modified oligonucleotides have been identified. [26] In particular, we have used an activity-based phage-display selection system to evolve av ariant of the Stoffel fragment of TaqD NA polymerase,S FM4-3, that transcribes and reverse transcribes oligonucleotides with 2'-OMe substituents and that efficiently PCR amplifies oligonucleotides with one or more of the nucleotides modified with a2'-F substituent.…”

Customised nucleic acid libraries for enhanced aptamer selection and performance

“…By now, three different groups published well-characterized novel base pairs with properties that allow their use in aptamer selections: Romesberg's group is working with dNaMd5SICS (dNaM: 1,4-Anhydro-2-deoxy-1-C-(3-methoxy-2-naphthalenyl)-(1R)-D-erythro-pentitol, d5SICS: 2-((2R,4R,5R)-tetrahydro-4-hydroxy-5-(hydroxymethyl) furan-2-yl)-6-methylisoquinoline-1(2H)-thione), Hirao and co-workers have published dDs-dPx (Ds: 7-(2-thienyl)imidazo [4,5-b]pyridine, Px: 2-nitro-4-propynylpyrrole), and Benner's laboratory is utilizing the dZ-dP (dZ: 6-amino-5-nitro-3- (Figure 4). While the interaction of the dZ-dP pair is based on hydrogen bonding, similar to the interaction between the natural base pairs (Figure 4a,b), the other two pairs interact through hydrophobic and packing forces (Figure 4c,d) [8]. dNaM-d5SICS has not yet been used for aptamer selections.…”