Успехи применения модифицированных нуклеотидов в технологии SELEX

Сноски

* Адресат для корреспонденции.

Вклад авторов

О.М. Антипова и Р.В. Решетников собрали материал и написали текст данного сообщения, А.М. Копылов определил основную направленность обзора, Е.Г. Завьялова обеспечила анализ собранного материала, Г.В. Павлова и А.В. Головин отредактировали текст данного сообщения.

Финансирование

Настоящее исследование было финансировано Министерством образования и науки РФ (RFMEF157617X0095).

Благодарности

Коллектив авторов благодарит Ю.И. Логинова и В.Е. Бабия за поддержку.

Список литературы

1. Farzin, L., Shamsipur, M., and Sheibani, S. (2017) A review: aptamer-based analytical strategies using the nanomaterials for environmental and human monitoring of toxic heavy metals, Talanta, 174, 619–627.

2. Pichon, V., Brothier, F., and Combes, A. (2015) Aptamer-based-sorbents for sample treatment – a review, Anal. Bioanal. Chem., 407, 681–698.

3. Batool, S., Bhandari, S., George, S., Okeoma, P., Van, N., Zumrut, H., and Mallikaratchy, P. (2017) Engineered aptamers to probe molecular interactions on the cell surface, Biomedicines, 5, 54.

4. Zhou, W., Jimmy Huang, P.-J., Ding, J., and Liu, J. (2014) Aptamer-based biosensors for biomedical diagnostics, Analyst, 139, 2627.

5. Meng, H.-M., Liu, H., Kuai, H., Peng, R., Mo, L., and Zhang, X.-B. (2016) Aptamer-integrated DNA nanostructures for biosensing, bioimaging and cancer therapy, Chem. Soc. Rev., 45, 2583–2602.

6. Stein, C.A., and Castanotto, D. (2017) FDA-approved oligonucleotide therapies in 2017, Mol. Ther., 16, 1069–1075.

7. Zhou, J., and Rossi, J. (2016) Aptamers as targeted therapeutics: current potential and challenges, Nat. Rev. Drug Discov., 16, 181–202.

8. Robertson, D.L., and Joyce, G.F. (1990) Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA, Nature, 344, 467–468.

9. Tuerk, C., and Gold, L. (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase, Science, 249, 505–510.

10. Ellington, A.D., and Szostak, J.W. (1990) In vitro selection of RNA molecules that bind specific ligands, Nature, 346, 818–822.

11. Sun, H., and Zu, Y. (2015) Highlight of recent advances in aptamer technology and its application, Molecules, 20, 11959–11980.

12. Bouchard, P.R., Hutabarat, R.M., and Thompson, K.M. (2010) Discovery and development of therapeutic aptamers, Annu. Rev. Pharmacol. Toxicol., 50, 237–257.

13. Forster, C., Zydek, M., Rothkegel, M., Wu, Z., Gallin, C., Gessner, R., Lisdat, F., and Furste, J.P. (2012) Properties of an LNA-modified ricin RNA aptamer, Biochem. Biophys. Res. Commun., 419, 60–65.

14. Ruckman, J., Green, L.S., Beeson, J., Waugh, S., Gillette, W.L., Henninger, D.D., Claesson-Welsh, L., and Janjic, N. (1998) 2′-Fluoropyrimidine RNA-based aptamers to the 165-amino acid form of vascular endothelial growth factor (VEGF165), J. Biol. Chem., 273, 20556–20567.

15. Ng, E.W.M., Shima, D.T., Calias, P., Cunningham, E.T., Guyer, D.R., and Adamis, A.P. (2006) Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease, Nat. Rev. Drug Discov., 5, 123–132.

16. Lipi, F., Chen, S., Chakravarthy, M., Rakesh, S., and Veedu, R.N. (2016) In vitro evolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies, RNA Biol., 13, 1232–1245.

17. Ni, S., Yao, H., Wang, L., Lu, J., Jiang, F., Lu, A., and Zhang, G. (2017) Chemical modifications of nucleic acid Aptamers for therapeutic purposes, Int. J. Mol. Sci., 18, 1683.

18. Hirao, I., Kimoto, M., and Lee, K.H. (2018) DNA aptamer generation by ExSELEX using genetic alphabet expansion with a mini-hairpin DNA stabilization method, Biochimie, 145, 15–21.

19. Vorobyeva, M., Davydova, A., Vorobjev, P., Pyshnyi, D., and Venyaminova, A. (2018) Key aspects of nucleic acid library design for in vitro selection, Int. J. Mol. Sci., 19, 470.

20. Perrin, D.M., Garestier, T., and Helene, C. (1999) Expanding the catalytic repertoire of nucleic acid catalysts: simultaneous incorporation of two modified deoxyribonucleoside triphosphates bearing ammonium and imidazolyl functionalities, Nucleosides Nucleotides, 18, 377–391.

21. Lapa, S.A., Chuinov, A.V., and Timofeev, E.N. (2016) The toolbox for modified aptamers, Mol. Biotechnol., 58, 79–92.

22. Lin, Y., Qiu, Q., Gill, S. C., and Jayasena, S.D. (1994) Modified RNA sequence pools for in vitro selection, Nucleic Acids Res., 22, 5229–5234.

23. Pagratis, N.C., Bell, C., Chang, Y.-F., Jennings, S., Fitzwater, T., Jellinek, D., and Dang, C. (1997) Potent 2′-amino-, and 2′-fluoro-2′-deoxyribonucleotide RNA inhibitors of keratinocyte growth factor, Nat. Biotechnol., 15, 68–73.

24. Hoshika, S., Minakawa, N., and Matsuda, A. (2004) Synthesis and physical and physiological properties of 4′-thioRNA: application to post-modification of RNA aptamer toward NF-kappaB, Nucleic Acids Res., 32, 3815–3825.

25. Kato, Y., Minakawa, N., Komatsu, Y., Kamiya, H., Ogawa, N., Harashima, H., and Matsuda, A. (2005) New NTP analogs: the synthesis of 4’-thioUTP and 4′-thioCTP and their utility for SELEX, Nucleic Acids Res., 33, 2942–2951.

26. Pinheiro, V.B., Taylor, A.I., Cozens, C., Abramov, M., Renders, M., Zhang, S., Chaput, J.C., Wengel, J., Peak-Chew, S.Y., McLaughlin, S.H., Herdewijn, P., and Holliger, P. (2012) Synthetic genetic polymers capable of heredity and evolution, Science, 336, 341–344.

27. Ferreira-Bravo, I.A., Cozens, C., Holliger, P., and DeStefano, J.J. (2015) Selection of 2′-deoxy-2′-fluoroarabinonucleotide (FANA) aptamers that bind HIV-1 reverse transcriptase with picomolar affinity, Nucleic Acids Res., 43, 9587–9599.

28. Kuwahara, M., Obika, S., Nagashima, J. I., Ohta, Y., Suto, Y., Ozaki, H., Sawai, H., and Imanishi, T. (2008) Systematic analysis of enzymatic DNA polymerization using oligo-DNA templates and triphosphate analogs involving 2′,4′-bridged nucleosides, Nucleic Acids Res., 36, 4257–4265.

29. Kasahara, Y., Irisawa, Y., Ozaki, H., Obika, S., and Kuwahara, M. (2013) 2′,4′-BNA/LNA aptamers: CE-SELEX using a DNA-based library of full-length 2′-O,4′-C-methylene-bridged/linked bicyclic ribonucleotides, Bioorganic Med. Chem. Lett., 23, 1288–1292.

30. Elle, I.C., Karlsen, K.K., Terp, M.G., Larsen, N., Nielsen, R., Derbyshire, N., Mandrup, S., Ditzel, H.J., and Wengel, J. (2015) Selection of LNA-containing DNA aptamers against recombinant human CD73, Mol. BioSyst., 11, 1260–1270.

31. Pasternak, A., Hernandez, F. J., Rasmussen, L. M., Vester, B., and Wengel, J. (2011) Improved thrombin binding aptamer by incorporation of a single unlocked nucleic acid monomer, Nucleic Acids Res., 39, 1155–1164.

32. Kotkowiak, W., Lisowiec-Wachnicka, J., Grynda, J., Kierzek, R., Wengel, J., and Pasternak, A. (2018) Thermodynamic, anticoagulant, and antiproliferative properties of thrombin binding aptamer containing novel UNA derivative, Mol. Ther. Nucleic Acids, 10, 304–316.

33. Yu, H., Zhang, S., Dunn, M.R., and Chaput, J.C. (2013) An efficient and faithful in vitro replication system for threose nucleic acid, J. Am. Chem. Soc., 135, 3583–3591.

34. Schoning, K.-U., Scholz, P., Guntha, S., Wu, X., Krishnamurthy, R., and Eschenmoser, A. (2000) Chemical etiology of nucleic acid structure: the alpha-threofuranosyl-(3’rightarrow 2′) oligonucleotide system, Science, 284, 2118–2124.

35. Vater, A., and Klussmann, S. (2015) Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer® therapeutics, Drug Discov. Today, 20, 147–155.

36. Yatime, L., Maasch, C., Hoehlig, K., Klussmann, S., Andersen, G.R., and Vater, A. (2015) Structural basis for the targeting of complement anaphylatoxin C5a using a mixed L-RNA/L-DNA aptamer, Nat. Commun., 6, 6481.

37. Wang, Z., Xu, W., Liu, L., and Zhu, T. F. (2016) A synthetic molecular system capable of mirror-image genetic replication and transcription, Nat. Chem., 8, 698–704.

38. Pech, A., Achenbach, J., Jahnz, M., Schulzchen, S., Jarosch, F., Bordusa, F., and Klussmann, S. (2017) A thermostable β-polymerase for mirror-image PCR, Nucleic Acids Res., 45, 3997–4005.

39. Eckstein, F. (2014) Phosphorothioates, essential components of therapeutic oligonucleotides, Nucleic Acid Ther., 24, 374–387.

40. King, D.J., Ventura, D.A., Brasier, A.R., and Gorenstein, D.G. (1998) Novel combinatorial selection of phosphorothioate oligonucleotide aptamers, Biochemistry, 37, 16489–16493.

41. Pallan, P.S., Yang, X., Sierant, M., Abeydeera, N.D., Hassell, T., Martinez, C., Janicka, M., Nawrot, B., and Egli, M. (2014) Crystal structure, stability and Ago2 affinity of phosphorodithioate-modified RNAs, RSC Adv., 4, 64901–64904.

42. Abeydeera, N.D., Egli, M., Cox, N., Mercier, K., Conde, J.N., Pallan, P.S., Mizurini, D.M., Sierant, M., Hibti, F.E., Hassell, T., Wang, T., Liu, F.W., Liu, H.M., Martinez, C., Sood, A.K., Lybrand, T.P., Frydman, C., Monteiro, R.Q., Gomer, R.H., Nawrot, B., and Yang, X. (2016) Evoking picomolar binding in RNA by a single phosphorodithioate linkage, Nucleic Acids Res., 44, 8052–8064.

43. Kanlikilicer, P., Ozpolat, B., Aslan, B., Bayraktar, R., Gurbuz, N., Rodriguez-Aguayo, C., Bayraktar, E., Denizli, M., Gonzalez-Villasana, V., Ivan, C., Lokesh, G.L.R., Amero, P., Catuogno, S., Haemmerle, M., Wu, S.Y.-Y., Mitra, R., Gorenstein, D.G., Volk, D.E., de Franciscis, V., Sood, A.K., and Lopez-Berestein, G. (2017) Therapeutic targeting of AXL receptor tyrosine kinase inhibits tumor growth and intraperitoneal metastasis in ovarian cancer models, Mol. Ther. Nucleic Acids, 9, 251–262.

44. Cerchia, L., Esposito, C.L., Camorani, S., Rienzo, A., Stasio, L., Insabato, L., Affuso, A., and De Franciscis, V. (2012) Targeting Axl with an high-affinity inhibitory ptamer, Mol. Ther., 20, 2291–2303.

45. Ellington, A.D., and Szostak, J.W. (1992) Selection in vitro of single-stranded DNA molecules that fold into specific ligand-binding structures, Nature, 355, 850–852.

46. Huizenga, D.E., and Szostak, J.W. (1995) A DNA aptamer that binds adenosine and ATP, Biochemistry, 34, 656–665.

47. Lato, S.M., Ozerova, N.D.S., He, K., Sergueeva, Z., Shaw, B.R., and Burke, D.H. (2002) Boron-containing aptamers to ATP, Nucleic Acids Res., 30, 1401–1407.

48. Barth, R.F., Soloway, A.H., Goodman, J.H., Gahbauer, R.A., Gupta, N., Blue, T.E., Yang, W.L., and Tjarks, W. (1999) Boron neutron capture therapy of brain tumors: Biodistribution, pharmacokinetics, and radiation dosimetry of sodium borocaptate in patients with gliomas, Neurosurgery, 44, 433–450.

49. Mutisya, D., Selvam, C., Kennedy, S.D., and Rozners, E. (2011) Synthesis and properties of triazole-linked RNA, Bioorganic Med. Chem. Lett., 21, 3420–3422.

50. Varizhuk, A.M., Tsvetkov, V.B., Tatarinova, O.N., Kaluzhny, D.N., Florentiev, V.L., Timofeev, E.N., Shchyolkina, A.K., Borisova, O.F., Smirnov, I.P., Grokhovsky, S.L., Aseychev, A.V., and Pozmogova, G.E. (2013) Synthesis, characterization and in vitro activity of thrombin-binding DNA aptamers with triazole internucleotide linkages, Eur. J. Med. Chem., 67, 90–97.

51. Latham, J.A., Johnson, R., and Toole, J.J. (1994) The application of a modified nucleotide in aptamer selection: novel thrombin aptamers containing 5-(1-pentynyl)-2′-deoxyuridine, Nucleic Acids Res., 22, 2817–2822.

52. Platella, C., Riccardi, C., Montesarchio, D., Roviello, G.N., and Musumeci, D. (2017) G-quadruplex-based aptamers against protein targets in therapy and diagnostics, Biochim. Biophys. Acta, 1861, 1429–1447.

53. Tucker, O.W., Shum, T.K., Tanner, A.J. (2012) G-quadruplex DNA aptamers and their ligands: structure, function and application, Curr. Pharm. Des., 18, 2014–2026.

54. Bock, L.C., Griffin, L.C., Latham, J.A., Vermaas, E.H., and Toole, J.J. (1992) Selection of single-stranded DNA molecules that bind and inhibit human thrombin, Nature, 355, 564–566.

55. Helm, M., and Alfonzo, J.D. (2014) Posttranscriptional RNA modifications: playing metabolic games in a cell’s chemical legoland, Chem. Biol., 21, 174–185.

56. Gregson, J.M., Crain, P.F., Edmonds, C.G., Gupta, R., Hashizume, T., Phillipson, D.W., and McCloskey, J.A. (1993) Structure of the archaeal transfer RNA nucleoside G*-15 (2-amino-4,7-dihydro-4-oxo-7-beta-D-ribofuranosyl-1H-pyrrolo[2,3-d]pyrimidine-5-carboximi dam ide (archaeosine)), J. Biol. Chem., 268, 10076–10086.

57. Vaish, N.K., Larralde, R., Fraley, A.W., Szostak, J.W., and McLaughlin, L.W. (2003) A novel, modification-dependent ATP-binding aptamer selected from an RNA library incorporating a cationic functionality, Biochemistry, 42, 8842–8851.

58. Masud, M.M., Kuwahara, M., Ozaki, H., and Sawai, H. (2004) Sialyllactose-binding modified DNA aptamer bearing additional functionality by SELEX, Bioorganic Med. Chem., 12, 1111–1120.

59. Hili, R., Niu, J., and Liu, D.R. (2013) DNA ligase-mediated translation of DNA into densely functionalized nucleic acid polymers, J. Am. Chem. Soc., 135, 98–101.

60. Guo, C., Watkins, C.P., and Hili, R. (2015) Sequence-defined scaffolding of peptides on nucleic acid polymers, J. Am. Chem. Soc., 137, 11191–11196.

61. Guo, C., and Hili, R. (2017) Fidelity of the DNA ligase-catalyzed scaffolding of peptide fragments on nucleic acid polymers, Bioconjug. Chem., 28, 314–318.

62. Li, M., Lin, N., Huang, Z., Du, L., Altier, C., Fang, H., and Wang, B. (2008) Selecting aptamers for a glycoprotein through the incorporation of the boronic acid moiety, J. Am. Chem. Soc., 130, 12636–12638.

63. Minagawa, H., Onodera, K., Fujita, H., Sakamoto, T., Akitomi, J., Kaneko, N., Shiratori, I., Kuwahara, M., Horii, K., and Waga, I. (2017) Selection, characterization and application of artificial DNA aptamer containing appended bases with sub-nanomolar affinity for a salivary biomarker, Sci. Rep., 7, 42716.

64. Henry, A.A., and Romesberg, F.E. (2005) The evolution of DNA polymerases with novel activities, Curr. Opin. Biotechnol., 16, 370–377.

65. Walsh, J.M., and Beuning, P.J. (2012) Synthetic nucleotides as probes of DNA polymerase specificity, J. Nucleic Acids, doi: 10.1155/2012/530963.

66. Chen, T., and Romesberg, F.E. (2014) Directed polymerase evolution, FEBS Lett., 588, 219–229.

67. Houlihan, G., Arangundy-Franklin, S., and Holliger, P. (2017) Engineering and application of polymerases for synthetic genetics, Curr. Opin. Biotechnol., 48, 168–179.

68. Hollenstein, M. (2012) Nucleoside triphosphates – building blocks for the modification of nucleic acids, Molecules, 17, 13569–13591.

69. Hocek, M. (2014) Synthesis of base-modified 2′-deoxyribonucleoside triphosphates and their use in enzymatic synthesis of modified DNA for applications in bioanalysis and chemical biology, J. Org. Chem., 79, 9914–9921.

70. Kore, A.R., and Srinivasan, B. (2013) Recent advances in the syntheses of nucleoside triphosphates, Curr. Org. Synth., 10, 903–934.

71. Iglesias, L.E., Lewkowicz, E.S., Medici, R., Bianchi, P., and Iribarren, A.M. (2015) Biocatalytic approaches applied to the synthesis of nucleoside prodrugs, Biotechnol. Adv., 33, 412–434.

72. Caton-Williams, J., Lin, L., Smith, M., and Huang, Z. (2011) Convenient synthesis of nucleoside 5’ triphosphates for RNA transcription, Chem. Commun., 47, 8142.

73. Caton-Williams, J., Hoxhaj, R., Fiaz, B., and Huang, Z. (2013) Use of a novel 5′-regioselective phosphitylating reagent for one-pot synthesis of nucleoside 5′-triphosphates from unprotected nucleosides, Curr. Protoc. Nucleic Acid Chem., 1, 30.

74. Dellafiore, M.A., Montserrat, J.M., and Iribarren, A.M. (2016) Modified nucleoside triphosphates for in vitro selection techniques, Front. Chem., 4, 18.

75. Darmostuk, M., Rimpelova, S., Gbelcova, H., and Ruml, T. (2014) Current approaches in SELEX: an update to aptamer selection technology, Biotechnol. Adv., 33, 1141–1161.

76. Gawande, B.N., Rohloff, J.C., Carter, J.D., von Carlowitz, I., Zhang, C., Schneider, D.J., and Janjic, N. (2017) Selection of DNA aptamers with two modified bases, Proc. Natl. Acad. Sci. USA, 114, 2898–2903.

77. Rohloff, J.C., Gelinas, A.D., Jarvis, T.C., Ochsner, U.A., Schneider, D.J., Gold, L., and Janjic, N. (2014) Nucleic acid ligands with protein-like side chains: modified aptamers and their use as diagnostic and therapeutic agents, Mol. Ther. Nucleic Acids, 3, e201.

78. Ren, X., Gelinas, A.D., Von Carlowitz, I., Janjic, N., and Pyle, A.M. (2017) Structural basis for IL-1α recognition by a modified DNA aptamer that specifically inhibits IL-1α signaling, Nat. Commun., 8, 1, 810.

79. Russell, T.M., Green, L.S., Rice, T., Kruh-Garcia, N.A., Dobos, K., De Groote, M.A., Hraha, T., Sterling, D.G., Janjic, N., and Ochsner, U.A. (2017) Potential of high-affinity, slow off-rate modified aptamer reagents for Mycobacterium tuberculosis proteins as tools for infection models and diagnostic applications, J. Clin. Microbiol., 55, 3072–3088.

80. Ganz, P., Heidecker, B., Hveem, K., Jonasson, C., Kato, S., Segal, M.R., Sterling, D.G., and Williams, S.A. (2016) Development and validation of a protein-based risk score for cardiovascular outcomes among patients with stable coronary heart disease, JAMA, 315, 2532.

81. De Groote, M.A., Sterling, D.G., Hraha, T., Russell, T., Green, L.S., Wall, K., Kraemer, S., Ostroff, R., Janjic, N., and Ochsner, U.A. (2017) Discovery and validation of a six-marker serum protein signature for the diagnosis of active pulmonary tuberculosis, J. Clin. Microbiol., 55, 3057–3071.

82. Abifadel, M., Varret, M., Rabes, J. P., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., Derre, A., Villeger, L., Farnier, M., Beucler, I., Bruckert, E., Chambaz, J., Chanu, B., Lecerf, J.M., Luc, G., Moulin, P., Weissenbach, J., Prat, A., Krempf, M., Junien, C., Seidah, N.G., and Boileau, C. (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia, Nat. Genet., 34, 154–156.

83. Lokesh, G.L., Wang, H., Lam, C.H., Thiviyanathan, V., Ward, N., Gorenstein, D.G., and Volk, D.E. (2017) X-Aptamer selection and validation, Methods Mol. Biol., 1632, 151–174.

84. He, W., Elizondo-Riojas, M.A., Li, X., Lokesh, G.L.R., Somasunderam, A., Thiviyanathan, V., Volk, D.E., Durland, R.H., Englehardt, J., Cavasotto, C.N., and Gorenstein, D.G. (2012) X-Aptamers: a bead-based selection method for random incorporation of drug-like moieties onto next-generation aptamers for enhanced binding, Biochemistry, 51, 8321–8323.

85. Mann, A.P., Bhavane, R.C., Somasunderam, A., Liz Montalvo-Ortiz, B., Ghaghada, K.B., Volk, D., Nieves-Alicea, R., Suh, K.S., Ferrari, M., Annapragada, A., Gorenstein, D.G., and Tanaka, T. (2011) Thioaptamer conjugated liposomes for tumor vasculature targeting, Oncotarget, 2, 298–304.

86. Volk, D.E., and Lokesh, G.L.R. (2017) Development of phosphorothioate DNA and DNA thioaptamers, Biomedicines, 5, 41.

87. Tolle, F., Brandle, G.M., Matzner, D., and Mayer, G. (2015) A versatile approach towards nucleobase-modified aptamers, Angew. Chemie Int. Ed. Eng., 54, 10971–10974.

88. Switzer, C., Moronev, S.E., and Benner, S.A. (1989) Enzymatic incorporation of a new base pair into DNA and RNA, J. Am. Chem. Soc., 111, 8322–8323.

89. Kimoto, M., Matsunaga, K.I., and Hirao, I. (2016), DNA Aptamer generation by genetic alphabet expansion SELEX (ExSELEX) using an unnatural base pair system in Nucleic Acid Aptamers (Mayer, G., ed.) Springer, pp. 47–60.

90. Sismour, A.M., and Benner, S.A. (2005) The use of thymidine analogs to improve the replication of an extra DNA base pair: a synthetic biological system, Nucleic Acids Res., 33, 5640–5646.

91. Morales, J.C., and Kool, E.T. (1998) Efficient replication between non-hydrogen-bonded nucleoside shape analogs, Nat. Struct. Biol., 5, 950–954.

92. McMinn, D.L., Ogawa, A.K., Wu, Y., Liu, J., Schultz, P.G., and Romesberg, F.E. (1999) Efforts toward expansion of the genetic alphabet: DNA polymerase recognition of a highly stable, self-pairing hydrophobic base, J. Am. Chem. Soc., 121, 11585–11586.

93. Kimoto, M., Kawai, R., Mitsui, T., Yokoyama, S., and Hirao, I. (2009) An unnatural base pair system for efficient PCR amplification and functionalization of DNA molecules, Nucleic Acids Res., 37, 14.

94. Georgiadis, M.M., Singh, I., Kellett, W.F., Hoshika, S., Benner, S.A., and Richards, N.G.J. (2015) Structural basis for a six nucleotide genetic alphabet, J. Am. Chem. Soc., 137, 6947–6955.

95. Sefah, K., Yang, Z., Bradley, K.M., Hoshika, S., Jimenez, E., Zhang, L., Zhu, G., Shanker, S., Yu, F., Turek, D., Tan, W., and Benner, S.A. (2014) In vitro selection with artificial expanded genetic information systems, Proc. Natl. Acad. Sci. USA, 111, 1449–1454.

96. Hirao, I., Kimoto, M., Mitsui, T., Fujiwara, T., Kawai, R., Sato, A., Harada, Y., and Yokoyama, S. (2006) An unnatural hydrophobic base pair system: site-specific incorporation of nucleotide analogs into DNA and RNA, Nat. Methods, 3, 729–735.

97. Kong, D., Yeung, W., and Hili, R. (2017) In vitro selection of diversely functionalized aptamers, J. Am. Chem. Soc., 139, 13977–13980.