アプタマー

アプタマー (Aptamer) is a nucleic acid molecule and the peptide which are specifically combined with specific molecules. I pick it from all over the huge library of the random sequence, but there is it in the natural world and is usually known as a revolving switch. It is studied from the basics to the application such as drug searches widely. Ribozyme and アプタマー which I decrypted exist, and a self-cleaving thing is known under target molecule existence. I am classified in nucleic acid (DNA, RNA) アプタマー, two kinds of ペプチドアプタマー when I greatly distribute it.

Table of contents

RNA, DNA アプタマー

Nucleic acid アプタマー is provided for evolution engineering, and the technique is known as the in vitro selection method or the SELEX method. Organic small molecule and protein, nucleic acid, cell, cellular tissue, the thing which is specifically combined with various aims such as the microbe exist. Nucleic acid アプタマー is considered for biotechnological application, the application to a drug as the living body material which is available for the molecular recognition for the antibody. I can compose nucleic acid アプタマー chemically and in a short time in vitro, and the point that there is little immunogenicity, or there is not at all is the advantage that there is not in an antibody.

In 1990, two laboratories developed artificial nucleic acid アプタマー independently and reported it. I decided RNA sequence to bind to the T4DNA polymerase selectively in the gold laboratory and named the development technique the SELEX method. On the other hand, I decided RNA sequence to be specifically connected in an organic pigment in the ショスタック laboratory and named it the in vitro selection method [¹]. The name アプタマー came from aptus of the Latin, and ショスタック named it as the ligands that a nucleic acid became the base [¹]. Two years later, ショスタック laboratory and ギリアド サイエンシズ company reported DNA アプタマー which targeted organic pigment and thrombin each using the in vitro selection method independently [²]. The essential difference does not exist between RNA and DNA as アプタマー, but DNA has a characteristic to be stable chemically.

Very, interestingly, the idea called in vitro selection comes up by the evolution system of the self-reproduction molecules called the Qbeta reproduction system by Sol Spiegelman more than 20 years ago [³]. Furthermore, I announce the system called the direct evolution method where Gerald Joyce made the cleavage of the ribozyme a hint one year before the in vitro selection method and SELEX method come up.

A large number of researchers challenged sorting of various アプタマー after nucleic acid アプタマー was discovered, and much application and discovery have been accomplished. Ellington (Ellington) laboratory and SomaLogic company of the University of Texas automated in vitro selection in 2001, and an experiment period was shortened dramatically from six weeks to 3rd.

The product made in man-made wound of nucleic acid アプタマー had a big influence on biology and the biotechnological field, but, about the concept of naturally occurring アプタマー, did not exist until I discovered the gene adjustment factor that Ronald breaker performed the molecular recognition called the revolving switch in 2002. The discovery of the new gene adjustment mechanism with the RNA led to the reinforcement of the RNA world hypothesis.

Both of DNA and RNA アプタマー show high affinity and specificity for various molecules. ^[4][⁵] [⁶], e.g., a ribozyme [⁷] thrombin [⁸] human immunodeficiency virus tat gene product (アプタマー for HIV TAR),^[9] hemin, ^[10] interferon γ, ^[11] blood vessel wall growth factor (VEGF),^[12] prostate-specific antigen (PSA), ^[13][14]dopamine ^[15] is reported with both of RNA アプタマー, DNA アプタマー each.

By the recent アプタマー-related pharmaceutical development, OSI Pharmaceutical company develops アプタマー (Macugen) about the treatment of aging-related macula degeneration, and it is approved as アプタマー medicine for the first time by FDA, and an examination is performed. In addition, MA-based Archemix company of Cambridge restrains rejection by using アプタマー for molecules such as thrombin of the blood coagulating agent after an operation and investigates it whether application to the diabetic retinopathy treatment caused by the platelet-derived growth factor is possibility.

In nucleic acid アプタマー which is not modified, it is eliminated the resolution during the bloodstream immediately by the function of enzyme nuclease and kidney (half-life: for from several minutes to several hours). The treatment of the organ which nucleic acid アプタマー including a symptom and the eyes which medicine is necessary for temporarily including the blood clotting can give as the applied use of アプタマー which is not modified directly attracts attention. In addition, the point that biodegradability has good can become the advantage when I think about application to in vivo video diagnosis. Schering AG company performs a study to apply アプタマー which bound to tenascin (tenauscin) to the video diagnosis of cancer. By introduction of various molecular ornamentation such as 2'-pyrimidine fluoride or the PEG chain, I was able to lengthen half-life of nucleic acid アプタマー by a unit in a week from 1st.

A database about the experiments of the in vitro selection method and SELEX method includes アプタマーデータベースカタログ of the Ellington laboratory.

ペプチドアプタマー

ペプチドアプタマー is the protein which was designed to inhibit a target molecule and interaction with other protein in a cell. Specifically, various types of peptide binds to the both ends of the frame of the target protein, and there are many takers in an annulation. ペプチドアプタマー with structural characteristics to be connected with two points can have high cohesion in comparison with an antibody.

The sorting of ペプチドアプタマー is carried out by the Two-hybrid method of the yeast unlike sorting of nucleic acid アプタマー.

References

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1. ^ ^{a b} Ellington AD, Szostak JW, "In vitro selection of RNA molecules that bind specific ligands.", Nature, 1990 Aug 30;346(6287): 818-22. PMID: 1697402
2. ^ Bock LC, Griffin LC, Latham JA, Vermaas EH, Toole JJ, "Selection of single-stranded DNA molecules that bind and inhibit human thrombin.", Nature, 1992 Feb 6,355 (6360): 564-6 PMID: 1741036
3. ^ Mills, DR; Peterson, RL; Spiegelman, S (July 1967). "An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule.". Proceedings of the National Academy of Sciences of the United States of America 58 (1): 217–24. doi: 10.1073/pnas.58.1.217. PMC 335620. It is http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=335620. PMID 5231602 
4. ^ Neves, M.A.D.; O. Reinstein, M.Saad, P.E. Johnson (2010). "Defining the secondary structural requirements of a cocaine-binding aptamer by a thermodynamic and mutation study." It is 9–16. doi: Biophys Chem 153 10.1016/j.bpc.2010.09.009. PMID 21035241. 
5. ^ Baugh, C.; D. Grate, C.Wilson (2000). "2.8 angstrom crystal structure of the malachite green aptamer.." J. Mol. Biol. 301: 117–128. doi: 10.1006/jmbi.2000.3951. PMID 10926496. 
6. ^ Dieckmann, T.; E. Fujikawa, X. Xhao, J. Szostak, J. Feigon (1995). "Structural Investigations of RNA and DNA aptamers in Solution." Journal of Cellular Biochemistry: 56-56. 
7. ^ Potty, A.; K. Kourentzi, H. Fang, G. Jackson, X. Zhang, G. Legge, R. Willson (2009). "Biophysical Characterization of DNA Aptamer Interactions with Vascular Endothelial Growth Factor.." It is 145–156. doi: Biopolymers 91 10.1002/bip.21097. PMID 19025993. 
8. ^ Long, S.; M. Long, R. White, B. Sullenger (2008). "Crystal structure of an RNA aptamer bound to thrombin." RNA 14 (2): 2504–2512. PMID 18971322. 
9. ^ Darfeuille, F.; S. Reigadas, J. Hansen, H. Orum, C. Di Primo, J. Toulme (2006). "Aptamers targeted to an RNA hairpin show improved specificity compared to that of complementary oligonucleotides.." It is 12076–12082. doi: Biochemistry 45 10.1021/bi0606344. PMID 17002307. 
10. ^ Liu, M.; T. Kagahara, H. Abe, Y. Ito (2009). "Direct In Vitro Selection of Hemin-Binding DNA Aptamer with Peroxidase Activity." Bulletin of the Chemical Society of Japan 82: 99–104. 
11. ^ Min, K.; M. Cho, S. Han, Y. Shim, J. Ku, C. Ban (2008). "A simple and direct electrochemical detection of interferon-gamma using its RNA and DNA aptamers.." It is 1819–1824. doi: Biosensors & Bioelectronics 23 10.1016/j.bios.2008.02.021. PMID 18406597. 
12. ^ Ng, E.W.M; D.T. Shima, P. Calias, E.T. Cunningham, D.R. Guyer, A.P. Adamis (2006). "Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease.." Nature Reviews Drug Discovery 5 (2): 123–132. doi: 10.1038/nrd1955. PMID 16518379. 
13. ^ Savory, N.; K. Abe, K. Sode, K. Ikebukuro (2010). "Selection of DNA aptamer against prostate specific antigen using a genetic algorithm and application to sensing.." It is doi: 1386-91 Biosensors & Bioelectronics 15 10.1016/j.bios.2010.07.057. PMID 20692149. 
14. ^ Jeong, S.; S.R. Han, Y.J. Lee, S.W. Lee (2010). "Selection of RNA aptamers specific to active prostate-specific antigen.." It is doi: 379-85 Biotechnology Letters 32 10.1007/s10529-009-0168-1. PMID 19943183. 
15. ^ Walsh, R.; M. DeRosa (2009). "Retention of function in the DNA homolog of the RNA dopamine aptamer.." It is 732–735. doi: Biochemical and Biophysical Research Communications 388 10.1016/j.bbrc.2009.08.084. PMID 19699181. 

• Hoppe-Seyler F, Butz K "Peptide aptamers: powerful new tools for molecular medicine.", J Mol Med. 2000, 78(8): 426-30.PMID: 11097111
• Carothers JM, Oestreich SC, Davis JH, Szostak JW, "Informational complexity and functional activity of RNA structures.", J Am Chem Soc. 2004 Apr 28;126(16): 5130-7. PMID: 15099096
• Cohen BA, Colas P, Brent R, "An artificial cell-cycle inhibitor isolated from a combinatorial library", PNAS 1998 Nov 24;95(24): 14,272-7. PMID: 9826690
• Binkowski BF, Miller RA, Belshaw PJ, "Ligand Regulated Peptides: A general approach for selection of ligand regulated peptide-protein interactions" Chem & Biol. 2005 July, 12 (7): 847-55 PMID: 16039531
• It is 252-258 Sullenger BA, Gilboa E, "Emerging clinical applications of RNA "Nature 2002, 418.
• It is 123-132 Ng EW, Shima DT, Calias P, Cunningham ET, Jr., Guyer DR, Adamis AP, "Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease" Nat Rev Drug Discov 2006, 5.

Outside link

• Ellington Lab. Aptamer Database

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