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Review
. 2010 Aug 9;15(8):5423-44.
doi: 10.3390/molecules15085423.

Molecular evolution of functional nucleic acids with chemical modifications

Masayasu Kuwahara  1 , Naoki Sugimoto
Affiliations
Review

Molecular evolution of functional nucleic acids with chemical modifications

Masayasu Kuwahara et al. Molecules. .

Abstract

Nucleic acids are attractive materials for creating functional molecules that have applications as catalysts, specific binders, and molecular switches. Nucleic acids having such functions can be obtained by random screening, typically using in vitro selection methods. These methods have helped explore the potential abilities of nucleic acids and steadily contributed to their evolution, i.e., creation of RNA/DNA enzymes, aptamers, and aptazymes. Chemical modification would be a key means to further increase their performance, e.g., expansion of function diversity, enhancement of activity, and improvement of biostability for biological use. Indeed, in the past two decades, random screening involving chemical modification, post-SELEX chemical modification, and rational design methods have been advanced, and combining and integrating these methods may produce a new class of functional nucleic acids. This review focuses on the effectiveness of chemical modifications on the evolution of nucleic acids as functional molecules and the outlook for related technologies.

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Figures

Figure 1
Figure 1
General scheme of in vitro selection using the library of modified RNA/DNA.
Figure 2
Figure 2
(a) Examples of modified nucleoside triphosphate analogs available for enzymatic RNA polymerization. (b) Examples of modified nucleoside triphosphate analogs available for polymerase chain reaction (PCR).
Figure 3
Figure 3
(a) Example of simultaneous incorporation of three different modified nucleoside triphosphates.In in vitro selection, a combination of PEX and PCR was used. (b) Effects of a modified group on nucleotide polymerization. The reaction B is far more inefficient than the reaction A.
Figure 4
Figure 4
(a) Schematic illustration of in vitro selection of thalidomide-binding modified DNA aptamers. (b) Structure minimization of the obtained modified DNA aptamer based on secondary structure prediction.
Figure 5
Figure 5
(a) Schematic illustration of random screening of DNA aptamers by non-SELEX selection. (b) Schematic illustration of MonoLEX random screening of DNA aptamers.
Figure 6
Figure 6
Modified nucleotides with unique chemical structures which act as a template in the polymerase reaction.
See this image and copyright information in PMC

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