Abstract
Aptamers, derived from the latin word aptus (meaning, “to fit”), are functional nucleic acid binding species that have been selected from combinatorial oligonucleotide libraries by a process known as in vitro selection.1,2 Since 1990, numerous high-affinity and highly specific aptamers have been selected against a wide variety of target molecules, such as small organics, peptides, proteins, and even supramolecular complexes, such as viruses or cells.3,4 Since aptamers have been shown to discriminate between even closely related isomers or different conformational states of the same protein,5,6 they are becoming an increasingly popular tool for molecular recognition that may eventually rival antibodies. Their utility has now been demonstrated in a number of analytical applications, such as flow cytometry,7,8 affinity probe capillary electrophoresis9, sandwich assays,10 capillary electrochromatography,11,12 affinity chromatography,13,14 and more generally as biosensors.15–18
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5.7. References
Ellington, A. D.; Szostak, J. W. In vitro selection of RNA molecules that bind specific ligands, Nature 1990, 346, 818–822.
Tuerk, C.; Gold, L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase, Science (Washington, D. C., 1883–) 1990, 249, 505–510.
Wilson, D. S.; Szostak, J. W. In vitro selection of functional nucleic acids, Annu. Rev. Biochem. 1999, 68, 611–647.
Famulok, M.; Mayer, G.; Blind, M. Nucleic acid aptamers-from selection in vitro to applications in vivo, Acc. Chem. Res. 2000, 33, 591–599.
Conrad, R.; Keranen, L. M.; Ellington, A. D.; Newton, A. C. Isozyme-specific inhibition of protein kinase C by RNA aptamers, J. Biol. Chem. 1994, 269, 32051–32054.
Seiwert, S. D.; Stines Nahreini, T.; Aigner, S.; Ahn, N. G.; Uhlenbeck, O. C. RNA aptamers as pathway-specific MAP kinase inhibitors, Chem. Biol. 2000, 7, 833–843.
Davis, K. A.; Abrams, B.; Lin, Y.; Jayasena, S. D. Use of a high affinity DNA ligand in flow cytometry, Nucleic Acids Res. 1996, 24, 702–706.
Davis, K. A.; Lin, Y.; Abrams, B.; Jayasena, S. D. Staining of cell surface human CD4 with 2′-F-pyrimidine-containing RNA aptamers for flow cytometry, Nucleic Acids Res. 1998, 26, 3915–3924.
German, I.; Buchanan, D. D.; Kennedy, R. T. Aptamers as ligands in affinity probe capillary electrophoresis, Anal. Chem. 1998, 70, 4540–4545.
Drolet, D. W.; Moon-McDermott, L.; Romig, T. S. An enzyme-linked oligonucleotide assay, Nat. Biotechnol. 1996, 14, 1021–1025.
Kotia, R. B.; Li, L.; McGown, L. B. Separation of nontarget compounds by DNA aptamers, Anal. Chem. 2000, 72, 827–831.
Rehder, M. A.; McGown, L. B. Open-tubular capillary electrochromatography of bovine beta-lactoglobulin variants A and B using an aptamer stationary phase, Electrophoresis 2001, 22, 3759–3764.
Romig, T. S.; Bell, C.; Drolet, D. W. Aptamer affinity chromatography: combinatorial chemistry applied to protein purification, J. Chromatogr. B Biomed. Sci. Appl. 1999, 731, 275–284.
Deng, Q.; German, I.; Buchanan, D.; Kennedy, R. T. Retention and separation of adenosine and analogues by affinity chromatography with an aptamer stationary phase, Anal. Chem. 2001, 73, 5415–5421.
Kleinjung, F.; Klussmann, S.; Erdmann, V. A.; Scheller, F. W.; Fuerste, J. P.; Bier, F. F. Binders in biosensors:high-affinity RNA for small analytes, Anal. Chem. 1998, 70, 328–331.
McCauley, T. G.; Hamaguchi, N.; Stanton, M. Aptamer-based biosensor arrays for detection and quantification of biological macromolecules, Anal. Biochem. 2003, 319, 244–250.
Hesselberth, J.; Robertson, M. P.; Jhaveri, S.; Ellington, A. D. In vitro selection of nucleic acids for diagnostic applications, J Biotechnol 2000, 74, 15–25.
Rajendran, M.; Ellington, A. D. Selecting nucleic acids for biosensor applications, Comb Chem High Throughput Screen 2002, 5, 263–270.
Conrad, R. C; Giver, L.; Tian, Y.; Ellington, A. D. In vitro selection of nucleic acid aptamers that bind proteins, Methods Enzymol. 1996, 267, 336–367.
Cox, J. C; Rudolph, P.; Ellington, A. D. Automated RNA selection, Biotechnol. Prog. 1998, 14, 845–850.
Jenison, R. D.; Gill, S. C; Pardi, A.; Polisky, B. High-resolution molecular discrimination by RNA, Science 1994, 263, 1425–1429.
Jayasena, S. D. Aptamers: an emerging class of molecules that rival antibodies in diagnostics, Clin. Chem. 1999, 45, 1628–1650.
Pavski, V.; Le, X. C. Detection of human immunodeficiency virus type 1 reverse transcriptase using aptamers as probes in affinity capillary electrophoresis, Anal. Chem. 2001, 73, 6070–6076.
Kawazoe, N.; Ito, Y.; Imanishi, Y. Bioassay using a labeled oligonucleotide obtained by in vitro selection, Biotechnol. Prog. 1997, 13, 873–874.
Burgstaller, P.; Kochoyan, M.; Famulok, M. Structural probing and damage selection of citrulline-and arginine-specific RNA aptamers identify base positions required for binding, Nucleic Acids Res. 1995, 23, 4769–4776.
Padmanabhan, K.; Padmanabhan, K. P.; Ferrara, J. D.; Sadler, J. E.; Tulinsky, A. The structure of alpha-thrombin inhibited by a 15-mer single-stranded DNA aptamer, J. Biol. Chem. 1993, 268, 17651–17654.
Hermann, T.; Patel, D. J. Adaptive recognition by nucleic acid aptamers, Science 2000, 287, 820–825.
Ye, X.; Gorin, A.; Frederick, R.; Hu, W.; Majumdar, A.; Xu, W.; McLendon, G.; Ellington, A.; Patel, D. J. RNA architecture dictates the conformations of a bound peptide, Chem. Biol. 1999, 6, 657–669.
Patel, D. J.; Suri, A. K. Structure, recognition and discrimination in RNA aptamer complexes with cofactors, amino acids, drugs and aminoglycoside antibiotics, Rev. Mol. Biotechnol. 2000, 74, 39–60.
Sassanfar, M.; Szostak, J. W. An RNA motif that binds ATP, Nature 1993, 364, 550–553.
Huizenga, D. E.; Szostak, J. W. A DNA aptamer that binds adenosine and ATP, Biochemistry 1995, 34, 656–665.
Jhaveri, S.; Kirby, R.; Conrad, R.; Maglott, E. J.; Bowser, M.; Kennedy, R. T.; Glick, G.; Ellington, A. D. Designed signaling aptamers that transduce molecular recognition to changes in fluorescence intensity, J. Am. Chem. Soc. 2000, 122, 2469–2473.
Yamana, K.; Ohtani, Y.; Nakano, H.; Saito, I. Bis-pyrene labeled DNA aptamer as an intelligent fluorescent biosensor, Bioorg. Med. Chem. Lett. 2003, 13, 3429–3431.
Jhaveri, S.; Rajendran, M.; Ellington, A. D. In vitro selection of signaling aptamers, Nat. Biotechnol. 2000, 18, 1293–1297.
Tyagi, S.; Kramer, F. R. Molecular beacons: probes that fluoresce upon hybridization, Nat. Biotechnol. 1996, 14, 303–308.
Tyagi, S.; Bratu, D. P.; Kramer, F. R. Multicolor molecular beacons for allele discrimination, Nat. Biotechnol. 1998, 16, 49–53.
Tan, W.; Fang, X.; Li, J.; Liu, X. Molecular beacons: a novel DNA probe for nucleic acid and protein studies, Chemistry 2000, 6, 1107–1111.
Fang, X.; Li, J. J.; Perlette, J.; Tan, W.; Wang, K. Molecular beacons: novel fluorescent probes, Anal. Chem. 2000, 72, 747A–753A.
Marras, S. A.; Kramer, F. R.; Tyagi, S. Multiplex detection of single-nucleotide variations using molecular beacons, Genet. Anal. 1999, 14, 151–156.
Lakowicz, J. R. Principles of Fluorescence Spectroscopy., 2 ed.; Kluwer Academic/Plenum Press: New York, N.Y., 1999.
Morrison, L. E. Homogeneous detection of specific DNA sequences by flourescence quenching and energy transfer, J. Fluorescence 1999, 9, 187–196.
Bock, L. C; Griffin, L. C; Latham, J. A.; Vermaas, E. H.; Toole, J. J. Selection of single-stranded DNA molecules that bind and inhibit human thrombin, Nature 1992, 355, 564–566.
Wu, Q.; Tsiang, M.; Sadler, J. E. Localization of the single-stranded DNA binding site in the thrombin anion-binding exosite, J. Biol. Chem. 1992, 267, 24408–24412.
Paborsky, L. R.; McCurdy, S. N.; Griffin, L. C; Toole, J. J.; Leung, L. L. The single-stranded DNA aptamer-binding site of human thrombin, J. Biol. Chem. 1993, 268, 20808–20811.
Macaya, R. F.; Waldron, J. A.; Beutel, B. A.; Gao, H.; Joesten, M. E.; Yang, M.; Patel, R.; Bertelsen, A. H.; Cook, A. F. Structural and functional characterization of potent antithrombotic oligonucleotides possessing both quadruplex and duplex motifs, Biochemistry 1995, 34, 4478–4492.
Tsiang, M.; Jain, A. K.; Dunn, K. E.; Rojas, M. E.; Leung, L. L.; Gibbs, C. S. Functional mapping of the surface residues of human thrombin, J. Biol. Chem. 1995, 270, 16854–16863.
Tasset, D. M.; Kubik, M. F.; Steiner, W. Oligonucleotide inhibitors of human thrombin that bind distinct epitopes, J. Mol. Biol. 1997, 272, 688–698.
Macaya, R. F.; Schultze, P.; Smith, F. W.; Roe, J. A.; Feigon, J. Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution, Proc. Natl. Acad. Sci. U S A 1993, 90, 3745–3749.
Schultze, P.; Macaya, R. F.; Feigon, J. Three-dimensional solution structure of the thrombin-binding DNA aptamer d(GGTTGGTGTGGTTGG), J. Mol. Biol. 1994, 235, 1532–1547.
Kelly, J. A.; Feigon, J.; Yeates, T. O. Reconciliation of the X-ray and NMR structures of the thrombin-binding aptamer d(GGTTGGTGTGGTTGG), J. Mol. Biol. 1996, 256, 417–422.
Hamaguchi, N.; Ellington, A.; Stanton, M. Aptamer beacons for the direct detection of proteins, Anal. Biochem. 2001, 294, 126–131.
Stojanovic, M. N.; de Prada, P.; Landry, D. W. Aptamer-based folding fluorescent sensor for cocaine, J. Am. Chem. Soc. 2001, 123, 4928–4931.
Fang, X.; Sen, A.; Vicens, M.; Tan, W. Synthetic DNA aptamers to detect protein molecular variants in a high-throughput fluorescence quenching assay, Chembiochem. 2003, 4, 829–834.
Li, J. J.; Fang, X.; Tan, W. Molecular aptamer beacons for real-time protein recognition, Biochem. Biophys. Res. Commun. 2002, 292, 31–40.
Nutiu, R.; Li, Y. Structure-switching signaling aptamers, J. Am. Chem. Soc. 2003, 125, 4771–4778.
Stojanovic, M. N.; de Prada, P.; Landry, D. W. Fluorescent sensors based on aptamer self-assembly, J. Am. Chem. Soc. 2000, 122, 11547–11548.
Yamamoto, R.; Baba, T.; Kumar, P. K. Molecular beacon aptamer fluoresces in the presence of Tat protein of HIV-1, Genes Cells 2000, 5, 389–396.
Merino, E. J.; Weeks, K. M. Fluorogenic resolution of ligand binding by a nucleic acid aptamer, J. Am. Chem. Soc. 2003, 125, 12370–12371.
Rajendran, M.; Ellington, A. D. In vitro selection of molecular beacons, Nucleic Acids Res. 2003, 31, 5700–5713.
Poddar, S. K. Detection of adenovirus using PCR and molecular beacon, J. Virol. Methods 1999, 82, 19–26.
Sokol, D. L.; Zhang, X.; Lu, P.; Gewirtz, A. M. Real time detection of DNA.RNA hybridization in living cells, Proc. Natl. Acad. Sci. U S A 1998, 95, 11538–11543.
Liu, X.; Tan, W. A fiber-optic evanescent wave DNA biosensor based on novel molecular beacons, Anal. Chem. 1999, 71, 5054–5059.
Steemers, F. J.; Ferguson, J. A.; Walt, D. R. Screening unlabeled DNA targets with randomly ordered fiberoptic gene arrays, Nat. Biotechnol. 2000, 18, 91–94.
Fang, X.; Li, J. J.; Tan, W. Using molecular beacons to probe molecular interactions between lactate dehydrogenase and single-stranded DNA, Anal. Chem. 2000, 72, 3280–3285.
Potyrailo, R. A.; Conrad, R. C; Ellington, A. D.; Hieftje, G. M. Adapting selected nucleic acid ligands (aptamers) to biosensors, Anal. Chem. 1998, 70, 3419–3425.
Fang, X.; Cao, Z.; Beck, T.; Tan, W. Molecular aptamer for real-time oncoprotein platelet-derived growth factor monitoring by fluorescence anisotropy, Anal. Chem. 2001, 73, 5752–5757.
Biran, I.; Rissin, D. M.; Ron, E. Z.; Walt, D. R. Optical imaging fiber-based live bacterial cell array biosensor, Anal. Biochem. 2003, 315, 106–113.
D’Orazio, P. Biosensors in clinical chemistry, Clin. Chim. Acta 2003, 334, 41–69.
Sapsford, K. E.; Rasooly, A.; Taitt, C. R.; Ligler, F. S. Detection of Campylobacter and Shigella species in food samples using an array biosensor., Anal. Chem. 2004, 76, 433–440.
Ramsay, G. DNA chips: state-of-the art, Nat. Biotechnol. 1998, 16, 40–44.
Eisen, M. B.; Brown, P. O. DNA arrays for analysis of gene expression, Methods Enzymol. 1999, 303, 179–205.
Cox, J. C; Hayhurst, A.; Hesselberth, J.; Bayer, T. S.; Georgiou, G.; Ellington, A. D. Automated selection of aptamers against protein targets translated in vitro: from gene to aptamer, Nucleic Acids Res. 2002, 30, el08.
Green, N. M. Avidin, Adv. Protein Chem. 1975, 29, 85–133.
Lavigne, J. J.; Savoy, S.; Clevenger, M. B.; Ritchie, J. E.; McDoniel, B.; Yoo, S. J.; Anslyn, E. V.; McDevitt, J. T.; Shear, J. B.; Neikirk, D. P. Solution-based analysis of multiple analytes by a sensor array: toward the development of an “Electronic tongue”. J. Am. Chem. Soc. 1998, 120, 6429–6430.
Buranda, T.; Huang, J.; Perez-Luna, V. H.; Schreyer, B.; Sklar, L. A.; Lopez, G. P. Biomolecular recognition on well-characterized beads packed in microfluidic channels, Anal. Chem. 2002, 74, 1149–1156.
Seong, G. H.; Crooks, R. M. Efficient mixing and reactions within microfluidic channels using microbead-supported catalysts, J. Am. Chem. Soc. 2002, 124, 13360–13361.
Fulton, R. J.; McDade, R. L.; Smith, P. L.; Kienker, L. J.; Kettman, J. R., Jr. Advanced multiplexed analysis with the FlowMetrix system, Clin. Chem. 1997, 43, 1749–1756.
Egner, B. J.; Rana, S.; Smith, H.; Bouloc, N.; Frey, J. G.; Brocklesby, W. S.; Bradley, M. Tagging in combinatorial chemistry: the use of colored and fluorescent beads, Chem. Comm. 1997, 8, 735–736.
Needels, M. C; Jones, D. G.; Tate, E. H.; Heinkel, G. L.; Kochersperger, L. M.; Dower, W. J.; Barrett, R. W.; Gallop, M. A. Generation and screening of an oligonucleotide-eneoded synthetic peptide library, Proc. Natl. Acad. Sci. U S A 1993, 90, 10700–10704.
Hakala, H.; Lonnberg, H. Time-resolved fluorescence detection of oligonucleotide hybridization on a single microparticle: covalent immobilization of oligonucleotides and quantitation of a model system, Bioconjug. Chem. 1997, 8, 232–237.
Hakala, H.; Heinonen, P.; Iitia, A.; Lonnberg, H. Detection of oligonucleotide hybridization on a single microparticle by time-resolved fluorometry: hybridization assays on polymer particles obtained by direct solid phase assembly of the oligonucleotide probes, Bioconjug. Chem. 1997, 8, 378–384.
Van Ness, J.; Kalbfleisch, S.; Petrie, C. R.; Reed, M. W.; Tabone, J. C; Vermeulen, N. M. A versatile solid support system for oligodeoxynucleotide probe-based hybridization assays, Nucleic Acids Res. 1991, 19, 3345–3350.
Storhoff, J. J.; Elghanian, R.; Mucic, R. C.; Mirkin, C. A.; Letsinger, R. L. One-pot colorimetric differentiation of polynucleotides with single base imperfections using gold nanoparticle probes., J. Am. Chem. Soc. 1998, 120, 1959–1964.
Lee, M.; Walt, D. R. A fiber-optic microarray biosensor using aptamers as receptors, Anal. Biochem. 2000, 282, 142–146.
Lin, Y.; Padmapriya, A.; Morden, K. M.; Jayasena, S. D. Peptide conjugation to an in vitro-selected DNA ligand improves enzyme inhibition, Proc. Natl. Acad. Sci. U S A 1995, 92, 11044–11048.
Knight, B. Ricin—a potent homicidal poison, Br. Med. J. 1979, 1, 350–351.
Lord, J. M.; Roberts, L. M.; Robertas, J. D. Ricin: structure, mode of action, and some current applications, Faseb J. 1994, 8, 201–208.
Vitetta, E. S.; Thorpe, P. E.; Uhr, J. W. Immunotoxins: magic bullets or misguided missiles?, Trends Pharmacol. Sci. 1993, 14, 148–154.
Hesselberth, J. R.; Miller, D.; Robertas, J.; Ellington, A. D. In vitro selection of RNA molecules that inhibit the activity of ricin A-chain, J. Biol. Chem. 2000, 275, 4937–4942.
Narang, U.; Anderson, G. P.; Ligler, F. S.; Burans, J. Fiber optic-based biosensor for ricin, Biosens. Bioelectron. 1997, 12, 937–945.
Rowe-Taitt, C. A.; Hazzard, J. W.; Hoffman, K. E.; Cras, J. J.; Golden, J. P.; Ligler, F. S. Simultaneous detection of six biohazardous agents using a planar waveguide array biosensor, Biosens. Bioelectron. 2000, 15, 579–589.
Taitt, C. R.; Anderson, G. P.; Lingerfelt, B. M.; Feldstein, M. J.; Ligler, F. S. Nine-analyte detection using an array-based biosensor, Anal. Chem. 2002, 74, 6114–6120.
Delehanty, J. B.; Ligler, F. S. A microarray immunoassay for simultaneous detection of proteins and bacteria, Anal. Chem. 2002, 74, 5681–5687.
Poli, M. A.; Rivera, V. R.; Hewetson, J. F.; Merrill, G. A. Detection of ricin by colorimetric and chemiluminescence ELISA, Toxicon 1994, 32, 1371–1377.
Li, Y.; Nath, N.; Reichert, W. M. Parallel comparison of sandwich and direct label assay protocols on cytokine detection protein arrays, Anal. Chem. 2003, 75, 5274–5281.
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Cho, E.J., Rajendran, M., Ellington, A.D. (2005). Aptamers as Emerging Probes for Macromolecular Sensing. In: Geddes, C.D., Lakowicz, J.R. (eds) Advanced Concepts in Fluorescence Sensing. Topics in Fluorescence Spectroscopy, vol 10. Springer, Boston, MA. https://doi.org/10.1007/0-387-23647-3_5
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