リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Development of fluorogenic peptide probes carrying internally-incorporated cyanine dyes as FID indicators for dsRNAs」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
リケラボ

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Development of fluorogenic peptide probes carrying internally-incorporated cyanine dyes as FID indicators for dsRNAs

Lee En Ting Tabitha 東北大学

2022.09.26

概要

This thesis consists of four chapters.

In Chapter 1, I expounded on the dsRNA-targeting probe scene that serves as the backdrop for both Chapters 2 and 3. New analytical methods for double-stranded RNA (dsRNA) need to be developed to overcome problems such as poor selectivity or perturbation / destruction of the native dsRNA structure. To that end, I designed two fluorogenic peptide probes – the small molecule – PNA oligomer conjugate (SPOC) probe and the light-up peptide indicator (LUPI). These two probes both have a thiazole orange (TO) fluorophore that is internally-incorporated into the probe. Both probes were designed to be used as fluorescent indicators in a fluorescent indicator displacement (FID) assay to screen for new small molecules that could potentially act as drugs that target dsRNA. The mechanism for the FID assay as well as characteristics of good FID indicators were also discussed.

Chapter 2. The first dsRNA target we chose was the bacterial ribosomal RNA acceptor site (bac rRNA Asite). The bac rRNA A-site is the proofreading centre of the bacterial ribosome, and thus has been an attractive drug target for many decades. It contains an internal loop flanked by dsRNA regions. In this chapter, we designed the small molecule – PNA oligomer conjugate (SPOC) probe to simultaneously bind to the internal loop and the dsRNA region by a simple conjugation strategy between ATMND-C2-NH2 (internal loop binder) and a tFIT probe. The SPOC probe was expected to form a triplex with the bacteria rRNA A-site through Hoogsteen base-pairing, with the ATMND moiety binding to the internal loop.

This conjugation strategy, although simple, worked impressively. Notably, the SPOC probe was able to bind to the dsRNA target even at a neutral pH, which is an unfavourable condition for Hoogsteen basepairing. This was because the conjugated ATMND moiety was able to act as an anchor, facilitating binding even at pH 7.0. The probe was measured to have a dissociation constant (Kd) of 190 ± 72 nM and bound specifically to the bac rRNA A-site over the corresponding human rRNA A-sites. Lastly, we showed how the SPOC probe had potential as an FID indicator by conducting a mock FID assay, where the degree of displacement was in good correlation with the reported Kd values of the test compounds.

However, the SPOC probe design has its drawbacks. The lack of information about small molecules that can specifically bind to RNA structural features as well as the need for a homopurine stretch of RNA for Hoogsteen-base pairing limits the dsRNA targets that SPOC can be applied to.

Thus, in Chapter 3, we turned to a new probe design – LUPI. This time, instead of targeting a dsRNA, we targeted a ribonucleoprotein (RNP) complex (RNA + RNA-binding protein, RBP). As such, LUPI was designed to be a peptide indicator based on a well-known RNP complex– the HIV-1 Tat protein – HIV-1 TAR RNA model. The Tat protein binds to the TAR RNA to greatly enhance viral transcription. Without the Tat-TAR interaction, gene expression and replication are adversely affected. Hence, finding Tat-TAR inhibitors is an attractive therapeutic strategy. Unlike SPOC, LUPI is made up of amino acids, with its internally-incorporated TO acting as a surrogate amino acid, something that has never been reported before. Its amino acid sequence is based on the arginine rich motif (ARM) of the Tat protein, the part that is responsible for binding to TAR RNA.

By comparing LUPI with three other probes, one of which was the original Tat peptide fluorescent indicator, we showed that LUPI has superior light-up response, binding affinity (Kd = 1.0 ± 0.6 nM) and selectivity towards the TAR RNA over two other unrelated RNAs. Moreover, in a mock FID assay with five test compounds, only the test compound with a Kd comparable to LUPI’s was able to displace it, highlighting LUPI’s ability to sieve out super-strong binders.

Finally, in Chapter 4, I summarized my findings for the SPOC and LUPI probes as well as provide some thoughts about how these two probes can be tailored for other specific dsRNA targets, as well as other possible ways to develop the probe designs even further.

論文の公開元へ

この論文で使われている画像

関連論文

関連論文をもっと見る

参考文献

Chapter1

Aramburu, J., Navas-Castillo, J., Moreno, P., & Cambra, M. (1991). Detection of double-stranded RNA by ELISA and dot immunobinding assay using an antiserum to synthetic polynucleotides. Journal Of Virological Methods, 33(1-2), 1-11.

Balmith, M., Faya, M., & Soliman, M. (2016). Ebola virus: A gap in drug design and discovery - experimental and computational perspective. Chemical Biology & Drug Design, 89(3), 297-308.

Bood, M., del Nogal, A., Nilsson, J., Edfeldt, F., Dahlén, A., & Lemurell, M. et al. (2021). InterbaseFRET binding assay for pre-microRNAs. Scientific Reports, 11(1), 9396.

Cobb M (2017) 60 years ago, Francis Crick changed the logic of biology. PLoS Biology 15(9): e2003243.

Connelly, C., Moon, M., & Schneekloth, J. (2016). The Emerging Role of RNA as a Therapeutic Target for Small Molecules. Cell Chemical Biology, 23(9), 1077-1090.

Hangauer, M., Vaughn, I., & McManus, M. (2013). Pervasive Transcription of the Human Genome Produces Thousands of Previously Unidentified Long Intergenic Noncoding RNAs. Plos Genetics, 9(6), e1003569.

Jiang, L., Watkins, D., Jin, Y., Gong, C., King, A., & Washington, A. et al. (2015). Rapid Synthesis, RNA Binding, and Antibacterial Screening of a Peptidic-Aminosugar (PA) Library. ACS Chemical Biology, 10(5), 1278-1289.

Kobayashi, K., Tomita, R., & Sakamoto, M. (2009). Recombinant plant dsRNA-binding protein as an effective tool for the isolation of viral replicative form dsRNA and universal detection of RNA viruses. Journal Of General Plant Pathology, 75(2), 87-91.

Köhler, O., Jarikote, D., & Seitz, O. (2004). Forced Intercalation Probes (FIT Probes): Thiazole Orange as a Fluorescent Base in Peptide Nucleic Acids for Homogeneous Single-Nucleotide-Polymorphism Detection. Chembiochem, 6(1), 69-77.

Ku, J., Kim, S., Park, J., Kim, T., Kharbash, R., & Shin, E. et al. (2020). Reactive Polymer Targeting dsRNA as Universal Virus Detection Platform with Enhanced Sensitivity. Biomacromolecules, 21(6), 2440-2454.

Lo, C., Li, O., Tang, W., Hu, C., Wang, G., & Ngo, J. et al. (2018). Identification of influenza polymerase inhibitors targeting C-terminal domain of PA through surface plasmon resonance screening. Scientific Reports, 8(1), 2280.

Martin, W., Grandi, P., & Marcia, M. (2021). Screening strategies for identifying RNA- and ribonucleoprotein-targeted compounds. Trends In Pharmacological Sciences, 42(9), 758-771.

Mattick, J. (2004). RNA regulation: a new genetics?. Nature Reviews Genetics, 5(4), 316-323.

Mehyar, N., Mashhour, A., Islam, I., Gul, S., Adedeji, A., Askar, A., & Boudjelal, M. (2021). Using in silico modelling and FRET-based assays in the discovery of novel FDA-approved drugs as inhibitors of MERS-CoV helicase. SAR And QSAR In Environmental Research, 32(1), 51-70

Mills, N., Shelat, A., & Guy, R. (2007). Assay Optimization and Screening of RNA-Protein Interactions by AlphaScreen. SLAS Discovery, 12(7), 946-955.

Qu, G., Sun, X., Ying, N., Bu, S., Li, Z., & Hao, Z. et al. (2020). 16S rRNA‐functionalized multi‐HCR concatemers in a signal amplification nanostructure for visual detection of Salmonella. Biotechnology And Applied Biochemistry, 68(3), 560-567.

Shindy, H. (2017). Fundamentals in the chemistry of cyanine dyes: A review. Dyes And Pigments, 145, 505-513.

Stelzer, A., Frank, A., Kratz, J., Swanson, M., Gonzalez-Hernandez, M., & Lee, J. et al. (2011). Discovery of selective bioactive small molecules by targeting an RNA dynamic ensemble. Nature Chemical Biology, 7(8), 553-559.

Watkins, D., Jiang, L., Nahar, S., Maiti, S., & Arya, D. (2015). A pH Sensitive High-Throughput Assay for miRNA Binding of a Peptide-Aminoglycoside (PA) Library. PLOS ONE, 10(12), e0144251.

Østergaard, M., & Hrdlicka, P. (2011). Pyrene-functionalized oligonucleotides and locked nucleic acids (LNAs): Tools for fundamental research, diagnostics, and nanotechnology. Chemical Society Reviews, 40(12), 5771.

Zhang, J., Umemoto, S., & Nakatani, K. (2010). Fluorescent Indicator Displacement Assay for Ligand−RNA Interactions. Journal of The American Chemical Society, 132(11), 3660-3661.

Chapter2

Barbieri, C., Kaul, M., & Pilch, D. (2007). Use of 2-aminopurine as a fluorescent tool for characterizing antibiotic recognition of the bacterial rRNA A-site. Tetrahedron, 63(17), 3567-3574.

Carter, A., Clemons, W., Brodersen, D., Morgan-Warren, R., Wimberly, B., & Ramakrishnan, V. (2000). Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature, 407(6802), 340-348.

Chen, Y., Fan, Y., Tien, C., Yueh, A., & Chang, R. (2018). The conserved stem-loop II structure at the 3' untranslated region of Japanese encephalitis virus genome is required for the formation of subgenomic flaviviral RNA. PLOS ONE, 13(7), e0201250.

Chittapragada, M., Roberts, S., & Ham, Y. (2009). Aminoglycosides: Molecular Insights on the Recognition of RNA and Aminoglycoside Mimics. Perspectives In Medicinal Chemistry, 3, PMC.S2381.

D'Souza, V., Dey, A., Habib, D., & Summers, M. (2004). NMR Structure of the 101-nucleotide Core Encapsidation Signal of the Moloney Murine Leukemia Virus. Journal Of Molecular Biology, 337(2), 427-442.

Dudek, M., Romanowska, J., Wituła, T., & Trylska, J. (2014). Interactions of amikacin with the RNA model of the ribosomal A-site: Computational, spectroscopic and calorimetric studies. Biochimie, 102, 188-202.

Forge, A., & Schacht, J. (2000). Aminoglycoside Antibiotics. Audiology and Neurotology, 5(1), 3-22

Garneau-Tsodikova, S., & Labby, K. (2016). Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives. Medchemcomm, 7(1), 11-27.

Gupta, P., Zengeya, T., & Rozners, E. (2011). Triple helical recognition of pyrimidine inversions in polypurine tracts of RNA by nucleobase-modified PNA. Chemical Communications, 47(39), 11125.

Han, T. (2022). Synthesis and evaluation of new triplex-forming PNA-based fluorogenic probes targeting the bacterial rRNA A-site. 修士論文.

Hong, S., Harris, K., Fanning, K., Sarachan, K., Frohlich, K., & Agris, P. (2015). Evidence That Antibiotics Bind to Human Mitochondrial Ribosomal RNA Has Implications for Aminoglycoside Toxicity. Journal of Biological Chemistry, 290(31), 19273-19286.

Jana, S., & Deb, J. (2006). Molecular understanding of aminoglycoside action and resistance. Applied Microbiology and Biotechnology, 70(2), 140-150.

Kaul, M., & Pilch, D. (2002). Thermodynamics of Aminoglycoside−rRNA Recognition:  The Binding of Neomycin-Class Aminoglycosides to the A Site of 16S rRNA. Biochemistry, 41(24), 7695-7706.

Köhler, O., Jarikote, D., & Seitz, O. (2004). Forced Intercalation Probes (FIT Probes): Thiazole Orange as a Fluorescent Base in Peptide Nucleic Acids for Homogeneous Single-Nucleotide-Polymorphism Detection. Chembiochem, 6(1), 69-77.

Krause, K., Serio, A., Kane, T., & Connolly, L. (2016). Aminoglycosides: An Overview. Cold Spring Harbor Perspectives In Medicine, 6(6), a027029.

Lee, M., Bottini, A., Kim, M., Bardaro, M., Zhang, Z., & Pellecchia, M. et al. (2014). Correction: A novel small-molecule binds to the influenza A virus RNA promoter and inhibits viral replication. Chem. Commun., 50(83), 12578-12578.

Lin, J., Zhou, D., Steitz, T., Polikanov, Y., & Gagnon, M. (2018). Ribosome-Targeting Antibiotics: Modes of Action, Mechanisms of Resistance, and Implications for Drug Design. Annual Review of Biochemistry, 87(1), 451-478.

Macmaster, R., Zelinskaya, N., Savic, M., Rankin, C., & Conn, G. (2010). Structural insights into the function of aminoglycoside-resistance A1408 16S rRNA methyltransferases from antibiotic-producing and human pathogenic bacteria. Nucleic Acids Research, 38(21), 7791-7799.

Melnikov, S., Ben-Shem, A., Garreau de Loubresse, N., Jenner, L., Yusupova, G., & Yusupov, M. (2012). One core, two shells: bacterial and eukaryotic ribosomes. Nature Structural & Molecular Biology, 19(6), 560-567.

Mergny, J., Lacroix, L., Han, X., Leroy, J., & Helene, C. (1995). Intramolecular Folding of Pyrimidine Oligodeoxynucleotides into an i-DNA Motif. Journal of The American Chemical Society, 117(35), 8887- 8898.

Mingeot-Leclercq, M., Glupczynski, Y., & Tulkens, P. (1999). Aminoglycosides: Activity and Resistance. Antimicrobial Agents and Chemotherapy, 43(4), 727-737.

Neumann, K., Farnung, J., Baldauf, S., & Bode, J. (2020). Prevention of aspartimide formation during peptide synthesis using cyanosulfurylides as carboxylic acid-protecting groups. Nature Communications, 11(1).

Ogle, J., Brodersen, D., Clemons, W., Tarry, M., Carter, A., & Ramakrishnan, V. (2001). Recognition of Cognate Transfer RNA by the 30 S Ribosomal Subunit. Science, 292(5518), 897-902.

Pack, G., Wong, L., & Lamm, G. (1998). PKa of cytosine on the third strand of triplex DNA: Preliminary Poisson-Boltzmann calculations. International Journal Of Quantum Chemistry, 70(6), 1177-1184.

Pape T, Wintermeyer W, Rodnina MV. (2000) Conformational switch in the decoding region of 16S rRNA during aminoacyl-tRNA selection on the ribosome. Nat Struct Biol., 7(2), 104-7.

Ramakrishnan, V. (2002). Ribosome Structure and the Mechanism of Translation. Cell, 108(4), 557-572.

Ray, A., & Nordén, B. (2000). Peptide nucleic acid (PNA): its medical and biotechnical applications and promise for the future. The FASEB Journal, 14(9), 1041-1060.

Sato, T., Sato, Y., & Nishizawa, S. (2016). Triplex-Forming Peptide Nucleic Acid Probe Having Thiazole Orange as a Base Surrogate for Fluorescence Sensing of Double-stranded RNA. Journal of The American Chemical Society, 138(30), 9397-9400.

Sato, Y., Rokugawa, M., Ito, S., Yajima, S., Sugawara, H., Teramae, N., & Nishizawa, S. (2018). Fluorescent Trimethylated Naphthyridine Derivative with an Aminoalkyl Side Chain as the Tightest Nonaminoglycoside Ligand for the Bacterial A-site RNA. Chemistry - A European Journal, 24(52), 13862- 13870.

Sato, Y., Miura, H., Tanabe, T., Okeke, C., Kikuchi, A., & Nishizawa, S. (2022). Fluorescence Sensing of the Panhandle Structure of the Influenza A Virus RNA Promoter by Thiazole Orange Base SurrogateCarrying Peptide Nucleic Acid Conjugated with Small Molecule. Analytical Chemistry, 94(22), 7814- 7822.

Wang, C., Sato, Y., Kudo, M., Nishizawa, S., & Teramae, N. (2012). Ratiometric Fluorescent Signaling of Small Molecule, Environmentally Sensitive Dye Conjugates for Detecting Single-Base Mutations in DNA. Chemistry - A European Journal, 18(31), 9481-9484.

Chapter3

Aboul-ela, F., Karn, J., & Varani, G. (1995). The Structure of the Human Immunodeficiency Virus Type1 TAR RNA Reveals Principles of RNA Recognition by Tat Protein. Journal Of Molecular Biology, 253(2), 313-332.

Aboul-ela, F. (1996). Structure of HIV-1 TAR RNA in the absence of ligands reveals a novel conformation of the trinucleotide bulge. Nucleic Acids Research, 24(20), 3974-3981.

Anand, K., Schulte, A., Vogel-Bachmayr, K., Scheffzek, K., & Geyer, M. (2008). Structural insights into the Cyclin T1–Tat–TAR RNA transcription activation complex from EIAV. Nature Structural & Molecular Biology, 15(12), 1287-1292.

Barré-Sinoussi, F., Chermann, J., Rey, F., Nugeyre, M., Chamaret, S., & Gruest, J. et al. (1983). Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS). Science, 220(4599), 868-871.

Bradrick, T., & Marino, J. (2004). Ligand-induced changes in 2-aminopurine fluorescence as a probe for small molecule binding to HIV-1 TAR RNA. RNA, 10(9), 1459-1468.

Brannon, J., & Magde, D. (1978). Absolute quantum yield determination by thermal blooming. Fluorescein. The Journal Of Physical Chemistry, 82(6), 705-709.

Brodsky, A., & Williamson, J. (1997). Solution structure of the HIV-2 TAR-argininamide complex. Journal Of Molecular Biology, 267(3), 624-639.

Calnan, B., Tidor, B., Biancalana, S., Hudson, D., & Frankel, A. (1991). Arginine-Mediated RNA Recognition: the Arginine Fork. Science, 252(5009), 1167-1171.

Carpino, L., Shroff, H., Triolo, S., Mansour, E., Wenschuh, H., & Albericio, F. (1993). The 2,2,4,6,7- pentamethyldihydrobenzofuran-5-sulfonyl group (Pbf) as arginine side chain protectant. Tetrahedron Letters, 34(49), 7829-7832.

Carreon, J., Mahon,, K., & Kelley, S. (2004). Thiazole Orange−Peptide Conjugates:  Sensitivity of DNA Binding to Chemical Structure. Organic Letters, 6(4), 517-519.

Chaires, J. (1997). Energetics of drug–DNA interactions. Biopolymers, 44(3), 201-215

Chaloin, O., Peter, J., Briand, J., Masquida, B., Desgranges, C., Muller, S., & Hoebeke, J. (2005). The Nterminus of HIV-1 Tat protein is essential for Tat-TAR RNA interaction. CMLS Cellular And Molecular Life Sciences, 62(3), 355-361.

D’Agostino, V., Sighel, D., Zucal, C., Bonomo, I., Micaelli, M., & Lolli, G. et al. (2019). Screening Approaches for Targeting Ribonucleoprotein Complexes: A New Dimension for Drug Discovery. SLAS Discovery, 24(3), 314-331.

Debaisieux, S., Rayne, F., Yezid, H., & Beaumelle, B. (2011). The Ins and Outs of HIV-1 Tat. Traffic, 13(3), 355-363.

Delling, U., Roy, S., Sumner-Smith, M., Barnett, R., Reid, L., Rosen, C., & Sonenberg, N. (1991). The number of positively charged amino acids in the basic domain of Tat is critical for trans-activation and complex formation with TAR RNA. Proceedings Of the National Academy Of Sciences, 88(14), 6234- 6238.

Dingwall, C., Ernberg, I., Gait, M., Green, S., Heaphy, S., & Karn, J. et al. (1990). HIV-1 tat protein stimulates transcription by binding to a U-rich bulge in the stem of the TAR RNA structure. The EMBO Journal, 9(12), 4145-4153.

Dolicka, D., Sobolewski, C., Correia de Sousa, M., Gjorgjieva, M., & Foti, M. (2020). mRNA PostTranscriptional Regulation by AU-Rich Element-Binding Proteins in Liver Inflammation and Cancer. International Journal Of Molecular Sciences, 21(18), 6648.

Edwards, T., Robinson, B., & Sigurdsson, S. (2005). Identification of Amino Acids that Promote Specific and Rigid TAR RNA-Tat Protein Complex Formation. Chemistry & Biology, 12(3), 329-337.

Galarneau, A., & Richard, S. (2005). Target RNA motif and target mRNAs of the Quaking STAR protein. Nature Structural & Molecular Biology, 12(8), 691-698.

Gerstberger, S., Hafner, M., & Tuschl, T. (2014). A census of human RNA-binding proteins. Nature Reviews Genetics, 15(12), 829-845.

Greenbaum, N. (1996). How Tat targets TAR: structure of the BIV peptide–RNA complex. Structure, 4(1), 5-9.

Guo, Y., Wang, W., Sun, Y., Ma, C., Wang, X., & Wang, X. et al. (2016). Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein Reveals the Mechanism for Ribonucleoprotein Complex Formation. Journal Of Virology, 90(2), 1048-1061.

He, N., Liu, M., Hsu, J., Xue, Y., Chou, S., & Burlingame, A. et al. (2010). HIV-1 Tat and Host AFF4 Recruit Two Transcription Elongation Factors into a Bifunctional Complex for Coordinated Activation of HIV-1 Transcription. Molecular Cell, 38(3), 428-438.

Jeong, H., Choi, S., Kim, H., Park, J., Park, H., & Park, S. et al. (2013). Fluorescent peptide indicator displacement assay for monitoring interactions between RNA and RNA binding proteins. Molecular Biosystems, 9(5), 948-951.

Karn, J. (1999). Tackling tat. Journal Of Molecular Biology, 293(2), 235-254.

Kelly, M., Chu, C., Shi, H., Ganser, L., Bogerd, H., & Huynh, K. et al. (2020). Understanding the characteristics of nonspecific binding of drug-like compounds to canonical stem–loop RNAs and their implications for functional cellular assays. RNA, 27(1), 12-26.

Lee, M., Bottini, A., Kim, M., Bardaro, M., Zhang, Z., & Pellecchia, M. et al. (2014). A novel smallmolecule binds to the influenza A virus RNA promoter and inhibits viral replication. Chem. Commun., 50(3), 368-370.

Leroux, C., Cadoré, J., & Montelaro, R. (2004). Equine Infectious Anemia Virus (EIAV): what has HIV’s country cousin got to tell us?. Veterinary Research, 35(4), 485-512.

Matsumoto, C., Hamasaki, K., Mihara, H., & Ueno, A. (2000). A high-throughput screening utilizing intramolecular fluorescence resonance energy transfer for the discovery of the molecules that bind HIV-1 TAR RNA specifically. Bioorganic & Medicinal Chemistry Letters, 10(16), 1857-1861.

Mei, H., Galan, A., Halim, N., Mack, D., Moreland, D., & Sanders, K. et al. (1995). Inhibition of an HIV1 Tat-derived peptide binding to TAR RNA by aminoglycoside antibiotics. Bioorganic &Amp; Medicinal Chemistry Letters, 5(22), 2755-2760.

Metzger, A., Schindler, T., Willbold, D., Kraft, M., Steegborn, C., & Volkmann, A. et al. (1996). Structural rearrangements on HIV-1 Tat (32-72) TAR complex formation. FEBS Letters, 384(3), 255- 259.

Nathans, R., Cao, H., Sharova, N., Ali, A., Sharkey, M., & Stranska, R. et al. (2008). Small-molecule inhibition of HIV-1 Vif. Nature Biotechnology, 26(10), 1187-1192.

Patwardhan, N., Cai, Z., Newson, C., & Hargrove, A. (2019). Fluorescent peptide displacement as a general assay for screening small molecule libraries against RNA. Organic & Biomolecular Chemistry, 17(7), 1778-1786.

Peterlin, B., & Price, D. (2006). Controlling the Elongation Phase of Transcription with PTEFb. Molecular Cell, 23(3), 297-305.

Pugliese, A., Vidotto, V., Beltramo, T., Petrini, S., & Torre, D. (2005). A review of HIV-1 Tat protein biological effects. Cell Biochemistry And Function, 23(4), 223-227.

Puglisi, J., Tan, R., Calnan, B., Frankel, A., & Williamson, J. (1992). Conformation of the TAR RNAArginine Complex by NMR Spectroscopy. Science, 257(5066), 76-80.

Qi, L., Zhang, J., He, T., Huo, Y., & Zhang, Z. (2017). Probing interaction of a fluorescent ligand with HIV TAR RNA. Spectrochimica Acta Part A: Molecular And Biomolecular Spectroscopy, 173, 93-98.

Roy, S., Delling, U., Chen, C., Rosen, C., & Sonenberg, N. (1990). A bulge structure in HIV-1 TAR RNA is required for Tat binding and Tat-mediated trans-activation. Genes & Development, 4(8), 1365- 1373.

Sato, T., Sato, Y., & Nishizawa, S. (2016). Triplex-Forming Peptide Nucleic Acid Probe Having Thiazole Orange as a Base Surrogate for Fluorescence Sensing of Double-stranded RNA. Journal Of The American Chemical Society, 138(30), 9397-9400.

Sato, T., Sato, Y., & Nishizawa, S. (2017). Optimization of the Alkyl Linker of TO Base Surrogate in Triplex-Forming PNA for Enhanced Binding to Double-Stranded RNA. Chemistry - A European Journal, 23(17), 4079-4088.

Schulze-Gahmen, U., Echeverria, I., Stjepanovic, G., Bai, Y., Lu, H., & Schneidman-Duhovny, D. et al. (2016). Insights into HIV-1 proviral transcription from integrative structure and dynamics of the Tat:AFF4:P-TEFb:TAR complex. Elife, 5.

Shortridge, M., Wille, P., Jones, A., Davidson, A., Bogdanovic, J., & Arts, E. et al. (2018). An ultra-high affinity ligand of HIV-1 TAR reveals the RNA structure recognized by P-TEFb. Nucleic Acids Research, 47(3), 1523-1531.

Smirnov, A., Förstner, K., Holmqvist, E., Otto, A., Günster, R., & Becher, D. et al. (2016). Grad-seq guides the discovery of ProQ as a major small RNA-binding protein. Proceedings Of The National Academy Of Sciences, 113(41), 11591-11596.

Smirnov, A., Schneider, C., Hör, J., & Vogel, J. (2017). Discovery of new RNA classes and global RNAbinding proteins. Current Opinion In Microbiology, 39, 152-160.

Stelzer, A., Frank, A., Kratz, J., Swanson, M., Gonzalez-Hernandez, M., & Lee, J. et al. (2011). Discovery of selective bioactive small molecules by targeting an RNA dynamic ensemble. Nature Chemical Biology, 7(8), 553-559.

Suryawanshi, H., Sabharwal, H., & Maiti, S. (2010). Thermodynamics of Peptide−RNA Recognition: The Binding of a Tat Peptide to TAR RNA. The Journal Of Physical Chemistry B, 114(34), 11155-11163.

Tan, R., & Frankel, A. (1992). Circular dichroism studies suggest that TAR RNA changes conformation upon specific binding of arginine or guanidine. Biochemistry, 31(42), 10288-10294.

Tao, J., & Frankel, A. (1992). Specific binding of arginine to TAR RNA. Proceedings Of The National Academy Of Sciences, 89(7), 2723-2726.

Thomas, J., Ruggiero, A., Paxton, W., & Pollakis, G. (2020). Measuring the Success of HIV-1 Cure Strategies. Frontiers In Cellular And Infection Microbiology, 10.

Voss, S., Fischer, R., Jung, G., Wiesmüller, K., & Brock, R. (2006). A Fluorescence-Based Synthetic LPS Sensor. Journal Of The American Chemical Society, 129(3), 554-561.

Wang, S., Huber, P., Cui, M., Czarnik, A., & Mei, H. (1998). Binding of Neomycin to the TAR Element of HIV-1 RNA Induces Dissociation of Tat Protein by an Allosteric Mechanism. Biochemistry, 37(16), 5549-5557.

Wu, X., Lan, L., Wilson, D., Marquez, R., Tsao, W., & Gao, P. et al. (2015). Identification and Validation of Novel Small Molecule Disruptors of HuR-mRNA Interaction. ACS Chemical Biology, 10(6), 1476- 1484.

Zhang, X., Lee, S., Zhao, L., Xia, T., & Qin, P. (2010). Conformational distributions at the Npeptide/boxB RNA interface studied using site-directed spin labeling. RNA, 16(12), 2474-2483.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文
を
一発検索！

この論文の関連論文を見る