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Review
. 2015 Sep 14;20(9):16643-71.
doi: 10.3390/molecules200916643.

Generation of Aptamers with an Expanded Chemical Repertoire

Stella Diafa  1 , Marcel Hollenstein  2
Affiliations
Review

Generation of Aptamers with an Expanded Chemical Repertoire

Stella Diafa et al. Molecules. .

Abstract

The enzymatic co-polymerization of modified nucleoside triphosphates (dN*TPs and N*TPs) is a versatile method for the expansion and exploration of expanded chemical space in SELEX and related combinatorial methods of in vitro selection. This strategy can be exploited to generate aptamers with improved or hitherto unknown properties. In this review, we discuss the nature of the functionalities appended to nucleoside triphosphates and their impact on selection experiments. The properties of the resulting modified aptamers will be described, particularly those integrated in the fields of biomolecular diagnostics, therapeutics, and in the expansion of genetic systems (XNAs).

Keywords: SELEX; aptamers; chemically modified nucleic acids; modified nucleoside triphosphates; polymerases; synthetic genetic polymers; therapeutic oligonucleotides.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the SELEX strategy for the identification of DNA aptamers.
Figure 2
Figure 2
Chemical structures of 2′-modified nucleotides used in selection experiments to generate aptamers with enhanced pharmacokinetic properties: 2′-amino-NTPs 1, 2′-fluoro-NTPs 2, 2′-methoxy-NTPs 3, and 4′-thio-NTPs 4.
Figure 3
Figure 3
Chemical structure and numbering of the purine and pyrimidine nucleobases exemplified for ATP and UTP.
Figure 4
Figure 4
(a) Chemical structures of some base-modified dN*TPs used in aptamer selection experiments; (b) Target molecules camptothecin and thalidomide.
Figure 4
Figure 4
(a) Chemical structures of some base-modified dN*TPs used in aptamer selection experiments; (b) Target molecules camptothecin and thalidomide.
Figure 5
Figure 5
Schematic overview of the SELMA method. Figure adapted from reference [118].
Figure 6
Figure 6
Examples of the 5-modified deoxyuridine triphosphates used as building blocks for the generation of SOMAmers [58,122,125,126]. R groups: Bn-dU: benzyldeoxyuridine; dT*: methyl-dU (thymidine); iB-dU: isobutyldeoxyuridine; Th-dU: 2-thieno-methyl-propyl-deoxyuridine; FBn-dU: 4-fluoro-benzyl-deoxyuridine; Pe-dU: 2-Phenyl-ethyl-deoxyuridine; Pp-dU: 3-Phenyl-n-propyl-deoxyuridine; Tyr-dU: tyrosyl-deoxyuridine; Nap-dU: 1-naphtyldeoxyuridine; MBn-dU: 3,4-methyl-dioxy-benzyl-deoxyuridine; Bt-dU: 2-(3-benzo(b)thiophenyl)-ethyldeoxyuridine; 2Nap-dU: 2-naphtyldeoxyuridine; Ne-dU: 2-(1-naphtyl)-ethyldeoxyuridine; 2NE-dU: 2-(2-naphtyl)-ethyldeoxyuridine; Trp-dU: Tryptophanyldeoxyuridine.
Figure 7
Figure 7
The structures of the unnatural Ds:Px, P:Z, and d5SICS:dNaM base pairs.
Figure 8
Figure 8
Xeno Nucleic Acids (XNAs) and their structures.
See this image and copyright information in PMC

References

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