Abstract
Since nucleic acids (DNA and RNA) play very important roles in cells, they are molecular targets of many clinically used drugs, such as anticancer drugs and antibiotics. Because of clinical demands for treating various deadly cancers and drug-resistant strains of pathogens, there are urgent needs to develop novel therapeutic agents. Targeting nucleic acids hasn’t been the mainstream of drug discovery in the past, and the lack of 3D structural information for designing and developing drug specificity is one of the main reasons. Fortunately, many important structures of nucleic acids and their protein complexes have been determined over the past decade, which provide novel platforms for future drug design and discovery. In this review, we describe some useful nucleic acid structures, particularly their interactions with the ligands and therapeutic candidates or even drugs. We summarize important information for designing novel potent drugs and for targeting nucleic acids and protein-nucleic acid complexes to treat cancers and overcome the drug-resistant problems.
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Blundell TL. Structure-based drug design. Nature, 1996, 384: 23–26
Ghosh AK, Sridhar PR, Leshchenko S, Hussain AK, Li J, Kovalevsky AY, Walters DE, Wedekind JE, Grum-Tokars V, Das D, Koh Y, Maeda K, Gatanaga H, Weber IT, Mitsuya H. Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance. J Med Chem, 2006, 49(17): 5252–5261
Dahm R. Discovering DNA: Friedrich Miescher and the early years of nucleic acid research. Human Gen, 2008, 122(6): 565–581
Evan GI, Littlewood DT. The role of c-myc in cell growth. Curr Opin Genet Dev, 1993, 3: 44–49
David CJ, Chen M, Assanah M, Canoll P, Manley JL. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature, 2010, 463: 364–368
Gostissa M, Yan CT, Bianco JM, Cogné M, Pinaud E, Alt FW. Long-range oncogenic activation of Igh-c-myc translocations by the Igh 3· regulatory region. Nature, 2009, 462: 803–807
Orkin SH, Porcher C, Fujiwara Y, Visvader J, Wang LC. Intersections between blood cell development and leukemia genes. Cancer Res, 1999, 59(7): 1784–1787
Small MB, Hay N, Schwab M, Bishop JM. Neoplastic transformation by the human gene N-myc. Mol Cell Biol, 1987, 7(5): 1638–1645
Prescott JE, Osthus RC, Lee LA, Lewis BC, Shim H, Barrett JF, Guo Q, Hawkins AL, Griffin CA, Dang CV. A Novel c-Myc-responsive gene, jpo1, participates in neoplastic transformation. J Biol Chem, 2001, 276: 48276–48284
Katan T. Resistance to 3,5-dichlorophenyl-N-cyclic imide (’dicarboximide’) fungicides in the grey mould pathogen. Botrytis cinerea on protected crops. Plant Path, 1982, 31(2): 133–141
Threlfall EJ, Ward LR, Frost JA, Willshaw JA. The emergence and spread of antibiotic resistance in food-borne bacteria. Int J Food Microbiol, 2000, 62(1–2): 1–5
George AJ. Antimicrobial-resitant pathogens in the 1990s. Ann Rev Med, 1996, 47}: 169–1
Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med, 1999, 340: 1137–1143
Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med, 1999, 340: 1144–1153
Keys HM, Bundy BN, Stehman FB, Muder-spach LI, Chafe WE, Suggs CL, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma, N Engl J Med, 1999, 340: 1154–1161
Wang K, Lu JF, Li RC. The events that occur when cisplatin encounters cells. Coord Chem Rev, 1996, 151: 53–88
Lippard SJ. New chemistry of an old molecule: cis-[Pt(NH3)2Cl2]. Science, 1982, 218: 1075–1082
Takahara PM, Rosenzweig AC, Frederick CA, Lippard SJ. Crystal structure of double-stranded DNA containing the major adduct of the anticancer drug cisplatin. Nature, 1995, 377: 649–652
Zlatanova J, Yaneva J, Leuba SH. Proteins that specifically recognize cisplatin-damaged DNA: A clue to anticancer activity of cisplatin. FASEB J, 1998, 12: 791–799
Ohndorf UM, Rould MA, He Q, Pabo CO, Lippard SJ. Molecular basis for recognition of cisplatin-modified DNA by high-mobility group proteins. Nature, 1999, 399: 708–712
Farrell N, Kelland LR, Roberts JD, Van Beusichem M. Activation of the trans geometry in platinum antitumor complexes: A survey of the cytotoxicity of trans complexes containing planar ligands in murine L1210 and human tumor panels and studies on their mechanism of action. Cancer Res, 1992, 52: 5065–5072
Farrell N. Current status of structure-activity relationships of platinum anticancer drugs: Activation of the trans-geometry. Met Ions Biol Sys, 1996, 32: 603–639
Coluccia M, Nassi A, Loseto F, Boccarelli A, Mariggio MA, Giordano D, Intini FP, Caputo P, Natile G. A trans-platinum complex showing higher antitumor activity than the cis-congeners. J Med Chem, 1993, 36: 510–512
Najajreh Y, Khazanov E, Jawbry S, Ardeli-Tzaraf Y, Perez JM. Kasparkova J, Brabec V, Barenholz Y, Gibson D. Cationic nonsymmetric transplatinum complexes with piperidinopiperidine ligands. Preparation, characterization, in vitro cytotoxicity, in vivo toxicity, and anticancer efficacy studies. J Med Chem, 2006, 49: 4665–4673
Richards AD, Rodgers A. Synthetic metallomolecules as agents for the control of DNA structure. Chem Soc Rev, 2007, 36: 471–483
Frederick CA, Williams LD, Ughetto G, van der Marel GA, van Boom JH, Rich A, Wang AH. Structural comparison of anticancer drug-DNA complexes: Adriamycin and daunomycin. Biochemistry, 1990, 29: 2538–2549
Shi K, Pan B, Sundaralingam M. Structure of a B-form DNA/RNA chimera (dC)(rG)d(ATGG) complexed with daunomycin at 1.5A resolution. Acta Crystalloghr, Sect D, 2003, 59: 1377–1383
Wang AH, Gao YG, Liaw YC, Li YK. Formaldehyde cross-links daunorubicin and DNA efficiently: HPLC and X-ray diffraction studies. Biochemistry, 1991, 30: 3812–3815
Cuesta-Seijo JA, Sheldrick GM. Structures of complexes between echinomycin and duplex DNA. Acta Crystallogr, Sect D, 2005, 61: 442–448
Gao Q, Williams LD, Egli M, Rabinovich D, Chen SL, Quigley GJ, Rich A. Drug-induced DNA repair: X-ray structures of a DNA-ditercalinium complex. Proc Natl Acad Sci USA, 1991, 88: 2422–2426
Gao Q, Williams LD, Egli M, Rabinovic D, Chen SL, Quigley GL, Rich A, Wartell RM, Larson JE, Wells RE. Netropsin: A specific probe for AT regions of duplex deoxyribonucleic acid. J Biol Chem, 1974, 249: 6719–6731
Zimmer C. Effects of the antibiotics netropsin and distamycin A on the structure and function of nucleic acids. Mol Biol, 1975, 15: 285–318
Kopka ML, Yoon C, Goodsell D, Pjura P, Dickerson RE. The molecular origin of DNA-drug specificity in netropsin and distamycin. Proc Natl Acad Sci USA, 1985, 82(5): 1376–1380
Schultz PG, Dervan PB. Distamycin and penta-N-methylpyrroleca -rboxamide binding sites on native DNA. A comparison of methidiumpropyl-EDTA-Fe(II) footprinting and DNA affinity cleaving. J Biomol Struct Dyn, 1984, 1(5): 1133–1147
Nunn CM, Garman E, Neidle S. Crystal structure of the DNA decamer d(CGCAATTGCG) complexed with the minor groove binding drug netropsin. Biochemistry. 1997, 36(16): 4792–4799
Chen X, Mitra SN, Rao ST, Sekar K, Sundaralingam M. A novel end-to-end binding of two netropsins to the DNA decamers d(CCCCCIIIII)2, d(CCCBr5CCIIIII)2 and d(CBr5CCCCIIIII)2. Nucleic Acids Res, 1998, 26(23): 5464–5471
Pjura PE, Grzeskowiak K, Dickerson RE. Binding of Hoechst 33258 to the minor groove groove of B-DNA. J Mol Biol, 1987, 197: 257–271
Kopka ML, Yoon C, Goodsell D, Pjura P, Dickerson RE. Binding of an antitumor drug to DNA, Netropsin and C-G-C-G-A-A-T-T-BrC-G-C-G. J Mol Biol, 1985, 183: 553–563
Mitra SN, Wahl MC, Sundaralingam M. Structure of the side-by-side binding of distamycin tod(GTATATAC)2. Acta Crystallogr, Sect D, 1999, 55: 602–609
Chenoweth DM, Dervan PB. Allosterin modulation of DNA by small molecules. Proc Natl Acad Sci USA, 2009, 106: 13175–13179
Goodwin KD, Long EC, Georgiadis MM. A host-guest approach for determining drug-DNA interactions: An example using netropsin. Nucleic Acids Res. 2005, 33(13): 4106–4116
Nickols NG, Jacobs CS, Farkas ME, Dervan PB. Improved nuclear localization of DNA-binding polyamides. Nucleic Acids Res, 2007, 35: 363–370
Nickols NG, Dervan PB. Suppression of androgen receptormediated gene expression by a sequence-specific DNA-binding polyamide. Proc Natl Acad Sci USA, 2007, 104: 10418–10423
Jacobs CS, Dervan PB. Modifications at the C-terminus to improve pyrrole-imidazole polyamide activity in cell culture. J Med Chem. 2009, 52(23): 7380–7388
Le Doan T, Perrouault L, Praseuth D, Habhoub N, Decout JL, Thuong NT. Sequence-specific recognition, photocrosslinking and cleavage of the DNA double helix by an oligo-[alpha]-thymidylate covalently linked to an azidoproflavine derivative. Nucleic Acids Res, 1987, 15: 7749–7760
Moser HE, Dervan PB. Sequence-specific cleavage of double helical DNA by triple helix formation. Science, 1987, 238: 645–650
Malkov VA, Soyfer VN, Frank-Kamenetskii MD. Effect of intermolecular triplex formation on the yield of cyclobutane photodimers in DNA. Nucleic Acids Res, 1992, 20(18): 488948–95
Mirkin SM, Frank-Kamenetskii MD. H-DNA and related structures. Annu Rev Biophys Biomol Struct, 1994, 23: 541–576
Davis TL, Firulli AB, Kinniburgh AJ. Ribonucleoprotein and protein factors bind to an H-DNA-forming cmyc DNA element: Possible regulators of the c-myc gene. Proc Natl Acad Sci USA, 1989, 86: 9682–9686
Zain R, Sun JS. Do natural DNA triple-helical structures occur and function in vivo? Cell Mol Life Sci, 2003, 60: 862–870
Nielsen PE, Egholm M, Berg RH, Buchardt O. Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science, 1991, 254: 1497–1500
Menchise V, De Simone G, Tedeschi T, Corradini R, Sforza S, Marchelli R, Capasso D, Saviano M, Pedone C. Insights into peptide nucleic acid (PNA) structural features: the crystal structure of D-lysine-based chiral PNA-DNA duplex, Proc Natl Acad Sci USA, 2003 100, 12021–12026
Egholm M, Buchardt O, Christensen L, Behrens C, Freier SM, Driver DA, Berg RH, Kim SK, Norden B, Nielsen PE. PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogenbonding rules. Nature, 1993, 365: 566–568
Betts L, Josey JA, Veal JM, Jordan SR. A nucleic acid triplex formed by a nucleic acid-DNA complex. Science, 1995, 270: 1838–1841
Koppelhus U, Awasthi SK, Zachar V, Holst HU, Ebbesen P, Nielsen PE. Cell-dependent differential cellular uptake of PNA, peptides, and PNApeptide conjugates. Antisense Nucl Acid Drug Develop, 2002, 12: 51–63
Zhou P, Wang MM, Du L, Fisher GW, Waggoner A, Ly DH. Novel binding and efficient cellular uptake of guanidine-based peptide nucleic acids (GPNA). J Am Chem Soc, 2003, 125: 6878–6879
Dragulescu-Andrasi A, Zhou P, He GF, Ly DH. Cell-permeable GPNA with appropriate backbone stereochemistry and spacing binds sequencespecifically to RNA. Chem Comm, 2005, 244-246
McNeer NA, Chin JY, Schleifman EB, Fields RJ, Glazer PM, Saltzman WM. Nanoparticles deliver Triplex-forming PNAs for site-specific genomic recombination in CD34+ human hematopoietic progenitors. Mol Ther, 2010, doi:10.1038/mt.2010 doi:10.1038/mt.2010
Sinden RR, Potaman VN, Oussatcheva EA, Pearson CE, Lyubchenko YL, Shlyakhtenko LS. Triplet repeat DNA structures and human genetic disease: Dynamic mutations from dynamic DNA. J Biosci, 2002, 27(1): 53–65
Pearson CE, Sinden RR, Alternative structures in duplex DNA formed within the trinucleotide repeats of the myotonic dystrophy and fragile X loci. Biochemistry, 1996, 35: 5041–5053
Oleksy A, Blanco AG, Boer R, Usón I, Aymamí J, Rodger A, Hannon MJ, Coll M. Molecular recognition of a three-way DNA junction by a metallosupramolecular helicate. Angew Chem Int Ed Engl, 2006, 13: 45(8):1227–1231
Cerasino L, Hannon MJ, Sletten E. DNA three-way junction with a dinuclear iron(II) supramolecular helicate at the center: A NMR structural study. Inorg Chem, 2007, 46(16): 6245–6251
Ortiz-Lombardía M, González A, Eritja R, Aymamí J, Azorín F, Coll M. Crystal structure of a DNA Holliday junction. Nat Struct Biol, 1999, 6(10): 913–917
Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Cur§tin NJ, Helleday T, Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature, 2005, 434: 913–917
Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature, 2005 434: 917–921
Brogden AL, Hopcroft NH, Searcey M, Cardin CJ. Ligand bridging of the DNA Holliday junction: molecular recognition of a stacked-X four-way junction by a small molecule. Angew Chem Int Ed Engl. 2007, 46(21): 3850–3854.
Simonsson T, G-quadruplex DNA structures-variations on a theme. Biol Chem, 2001, 621-628
Schaffitzel C, Berger I, Postberg J, Hanes J, Lipps HJ, Pluckthun A. In vitro generated antibodies specific for telomeric guanine-quadruplex DNA react with Stylonychia lemnae macronuclei. Proc Natl Acad Sci USA, 2001, 98: 8572–8577
Parkinson GN, Lee MPH, Neidle S. Crystal structure of parallel quadruplexes from human telomeric DNA. Nature, 2002, 417: 876–880
Haider SM, Parkinson GN, Neidle S. Crystal structure of the potassiumform of an Oxytricha nova G-quadruplex. J Mol Biol, 2002, 320: 189–200
Gill ML, Strobel SA, Loria JP. Crystallization and characterization of the thallium form of the Oxytricha nova G-quadruplex, Nucleic Acids Res, 2006, 34: 4506–4514
Hazel P, Parkinson GN, Neidle S. Topology variation and loop structural homology in crystal and simulated structures of a bimolecular DNA quadruplex. J Am Chem Soc, 2006, 128: 5480–5487
Deng J, Xiong Y, Sundaralingam M. X-ray analysis of an RNA tetraplex (UGGGGU)(4) with divalent Sr(2þ) ions at subatomic resolution. Proc Natl Acad Sci USA, 2001, 98: 13665–13670
Pan B, Shi K, Sundaralingam M. Crystal structure of an RNA quadruplex containing inosine tetrad: Implications for the roles of NH2 group in purine tetrads. J Mol Biol, 2006, 363: 451–459
Phillips K, Dauter Z, Murchie AI, Lilley DM, Luisi B. The crystal structure of a parallel-stranded guanine tetraplex at 0.95 A resolution, J Mol Biol, 1997, 273: 171–182
Haider SM, Parkinson GN, Neidle S. Structure of a G-quadruplexligand complex. J Mol Biol, 2003, 326: 117–125
Clark GR, Pytel PD, Squire CJ, Neidle S. Structure of the first parallel DNA quadruplex complex. J Am Chem Soc, 2003, 125: 4066–4067
Parkinson GN, Ghosh R, Neidle S. Structural basis for binding of porphyrin to human telomeres. Biochemistry, 2007, 46: 2390–2397
Todd AK, Johnston M, Neidle S. Highly prevalent putative quadruplex sequence motifs in human DNA. Nucleic Acids Res, 2005, 33: 2901–2907
Huppert JL, Balasubramanian S. Prevalence of quadruplexes in the human genome. Nucleic Acids Res, 2005, 33: 2908–2916
Siddiqui-Jain A, Grand CL, Bearss DJ, Hurley LH. Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription, Proc Natl Acad Sci USA, 2002, 99: 11593–11598
Mandal M, Breaker RR. Gene regulation by riboswitches. Nat Rev Mol Cell Biol, 2004, 5: 451–463
Tucker BJ, Breaker RR. Riboswitches as versatile gene control elements. Curr Opin Struct Biol, 2005, 15: 342–348
Winkler WC, Breaker RR. Regulation of bacterial gene expression by riboswitches. Annu Rev Microbiol, 2005, 59: 487–517
Mandal M, Lee M, Barrick JE, Weinberg Z, Emilsson GM, Ruzzo WL, Breaker RR. A glycine-dependent riboswitch that uses cooperative binding to control gene expression. Science, 2004, 306: 275–279
Sudarsan N, Wickiser JK, Nakamura S, Ebert MS, Breaker RR. An mRNA structure in bacteria that controls gene expression by binding lysine. Genes Dev, 2003, 17: 2688–2697
Lee JM, Zhang SH, Saha S, Anna SS, Jiang C, Perkins J.. RNA expression analysis using an antisense Bacillus subtilis genome array. J Bacteriol, 2001, 183: 7371–7380
Lim J, Winkler WC, Nakamura S, Scott V, Breaker RR, Molecular-recognition characteristics of SAM-binding riboswitches. Angew Chem Int Ed Engl, 2006, 45: 964–968
Winkler WC, Cohen-Chalamish S, Breaker RR. An mRNA structure that controls gene expression by binding FMN. Proc Nat Acad Sci USA, 2002, 99: 15908–15913
Wickiser JK, Winkler WC, Breaker RR, Crothers DM. The speed of RNA transcription and metabolite binding kinetics operate an FMN riboswitch. Mol Cell, 2005, 18: 49–60.
Nahvi A, Barrick JE, Breaker RR. Coenzyme B12 riboswitches are widespread genetic control elements in prokaryotes. Nucleic Acids Res, 2004, 32: 143–150
Winkler W, Nahvi A, Breaker RR. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature, 2002, 419: 952–956
Rodionov DA, Vitreschak AG, Mironov AA, Gelfand MS. Comparative genomics of thiamin biosynthesis in procaryotes. New genes and regulatory mechanisms. J Biol Chem, 2002, 277: 48949–48959
Kulshina N, Baird NJ, Ferré-D`Amare AR. Recognition of the bacterial second messenger cyclic diguanylate by its cognateriboswitch. Nat Struct Mol Biol, 2009, 16: 1212–1217
Serganov A, Huang LL, Patel DJ. Conzyme recognition and gene regulation by a flavinmononucleotide riboswitch. Nature, 2009, 458: 233–237
Garst AD, Heroux A, Rambo RP, Batey RT. Crystal structure of the lysine riboswitch regulatory mRNA element. J Biol Chem, 2008, 283: 22347–22351
Klein DJ, Edwars TE, Ferré-D’Amare AR. Cocrystal structure of a class I preQ1 riboswitch reveals apseudoknot recognizing an essential hypermodifiednucleobase. Nat Struct Mol Biol, 2009, 16: 343
Robbins WJ. The pyridine analog of thiamine and the growth of fungi. Proc Natl Acad Sci USA, 1941, 27: 419–422
Woolley DW, White AGC. Selective reversible inhibition of microbial growth with pyrithiamine. J Exp Med, 1943, 78: 489–497
Shiota T, Folk JE, Tietze F. Inhibition of lysine utilization in bacteria by S-(betaaminoethyl) cysteine and its reversal by lysine peptides. Arch Biochem Biophys, 1958, 77; 372-377
McCord T, Ravel J, Skinner C, Shive W. dl-4-Oxalysine, an inhibitory analog of lysine. J Am Chem Soc, 1957, 79: 5693–5696
Matsui K, Wang HC, Hirota T, Matsukawa H, Kasai S. Riboflavin production by roseoflavin-resistant strains of some bacteria. Agric Biol Chem, 1982, 46: 2003–2008
Berezovskii VM, Stepanov AI, Polyakova NA, Tulchinskaya LS, Kukanova AY. Studies of a group of allo- and isoallxazine. XLVI. Synthesis and biological specificity of amino analogs. Bioorg Khim, 1977, 3: 521–524
Michel F, Umesono K, Ozeki H. Comparative and functional anatomy of group II catalytic introns a review. Gene, 1989, 82: 5–30
Cech TR. Self-splicing of group I introns. Annu Rev Biochem, 1990, 59: 543–568
Eckstein F, Bramlage B. The hammerhead ribozyme. Biopolymers, 1999, 52: 147–154
Ruffner D, Dahm S, Uhlenbeck O. Studies on the hammerhead RNA self-cleaving domain. Gene, 1989, 82(1): 31–41
Lazarev VN, Shmarov MM, Zakhartchouk AN, Yurov GK, Misurina OU, Akopian TA, Grinenko NF, Grodnitskaya NG, Kaverin NV, Naroditsky BS. Inhibition of influenza A virus reproduction by a ribozyme targeted against PB1 mRNA. Antiviral Res, 1999 42: 47–57
Sakamoto N, Wu CH, Wu GY. Intracellular cleavage of hepatitis C virus RNA and inhibition of viral protein translation by hammerhead ribozymes. J Clin Invest, 1996, 98: 2720–2728
Ideo G, Bellobuono A. New therapies for the treatment of chronic hepatitis C. Curr Pharm Des, 2002, 8: 959–966
Feng Y, Kong YY, Wang Y, Qi GR. Intracellular inhibition of the replication of hepatitis B virus by hammerhead ribozymes. J Gastroenterol Hepatol, 2001, 16: 1125–1130
Trang P, Lee K, Kiliani AF, Kim J, Liu F. Effective inhibition of herpes simplex virus 1 gene expression and growth by engineered RNase P ribozyme. Nucleic Acids Res, 2001, 29: 5071–5078
Trang P, Lee M, Nepomuceno E, Kim J, Zhu H, Liu F. Effective inhibition of human cytomegalovirus gene expression and replication by a ribozyme derived from the catalytic RNA subunit of RNase P from Escherichia coli. Proc Natl Acad Sci USA, 2000, 97: 5812–5817
Yamada O, Yu M, Yee JK, Kraus G, Looney D, Wong-Staal F. Intracellular immunization of human T cells with a hairpin ribozyme against human immunodeficiency virus type 1. Gene Ther, 1994, 1:34–45
Bai J, Banda N, Lee NS, Rossi J, Akkina R. RNA-based anti-HIV-1 gene therapeutic constructs in SCID-hu mouse model. Mol Ther, 2002, 6: 770–782
Akkina R, Banerjea A, Bai J, Anderson J, Li MJ, Rossi J. siRNAs, ribozymes and RNA decoys in modelling stem cell-based gene therapy for HIV/AIDS. Anticancer Res, 2003, 23: 1997–1005
Scherr M, Maurer AB, Klein S, Ganser A, Engels JW, Grez M. Effective reversal of a transformed phenotype by retrovirusmediated transfer of a ribozyme directed against mutant N-ras. Gene Ther, 1998, 5: 1227–1234
Schwab G, Chavany C, Duroux I, Goubin G, Lebeau J, Helene C, Saisonbehmoaras T. Antisense oligonucleotides adsorbed to polyalkylcyanoacrylate nanoparticles specifically inhibit mutated H-rasmediated cell proliferation and tumorigenicity in nude mice. Proc Natl Acad Sci USA, 1994, 91: 10460–10464
Bi F, Fan D, Hui H, Wang C, Zhang X. Reversion of the malignant phenotype of gastric cancer cells SGC7901 by c-erbB-2-specific hammerhead ribozyme. Cancer Gene Ther, 2001, 8: 835–842
Abounader R, Lal B, Luddy C, Koe G, Davidson B, Rosen EM, Laterra J. In vivo targeting of SF/HGF and c-met expression via U1snRNA/ribozymes inhibits glioma growth and angiogenesis and promotes apoptosis. FASEB J, 2002, 16: 108–110
Parthasarathy R, Cote GJ, Gagel RF. Hammerhead ribozymemediated inactivation of mutant RET in medullary thyroid carcinoma. Cancer Res, 1999, 59: 3911–3914
Deiner TO. Viroids and Viroid Diseases. New York: Wiley, 1979
Sheldon CC, Symons RH. Is hammerhead self-cleavage involved in the replication of a virusoid in vivo? Virology, 1993, 194(2): 463–474
Pease AC, Wemmer DE. Characterization of the secondary structure and melting of a self-cleaved RNA hammerhead domain by 1H NMR spectroscopy. Biochemistry, 1990, 29(38): 9039–9046
Hernández C, Flores R. Plus and minus RNAs of peach latent mosaic viroid self-cleave in vitro via hammerhead structures. Proc Natl Acad Sci USA, 1992, 89(9): 3711–3715
Hernández C, Daròs JA, Elena SF, Moya A, Flores R. The strands of both polarities of a small circular RNA from carnation self-cleave in vitro through alternative double- and single-hammerhead structures. Nucleic Acids Res, 1992, 20(23): 6323–6329
Stage TK, Hertel KJ, Uhlenbeck OC. Inhibition of the hammerhead ribozyme by neomycin. RNA. 1995, 1(1): 95–101
Dürckheimer W. Tetracyclines: Chemistry, biochemistry, and structure-activity relations. Angew Chem Int Ed Engl, 1975, 14 (11): 721–734
von Ahsen U, Davies J, Schroeder R. Antibiotic inhibition of group I ribozyme function. Nature. 1991, 353: 368–370
von Ahsen U, Davies J, Schroeder R. Non-competitive inhibition of group I intron RNA self-splicing by aminoglycoside antibiotics. J Mol Biol, 1992, 226(4): 935–941
Adams PL, Stahley MR, Kosek AB, Wang J, Strobel SA. Crystal structure of a self-splicing group I intron with both exons. Nature, 2004, 430: 45–50
Karn J. Tackling Tat. J Mol Biol, 1999, 293(2): 235–254
Zapp ML, Stern S, Green MR. Small molecules that selectively block RNA binding of HIV-1 Rev protein inhibit Rev function and viral production. Cell, 1993, 74(6): 969–978.
Faber C, Sticht H, Schweimer K, Rosch P. Structural rearrangements of HIV-1 Tat-responsive RNAupon binding of neomycin B. J Biol Chem, 2000, 275: 20660–20666
Davidson A, Leeper TC, Athanassiou Z, Patora-Komisarska K, Karn J, Robinson JA, Varani G. Stimultaneous recognition of HIV-1 TAR RNA bulge and loopsequences by cyclic peptide mimics of Tat protein. Proc Natl Acad Sci USA, 2009, 106: 11931–11936
Ogle JM, Carter AP, Ramakrishnan V. Insights into the decoding mechanism from recent ribosome structures. Trends Biochem Sci, 2003, 28: 259–266
Auerbach T, Bashan A, Yonath A. Ribosomal antibiotics:structural basis for resistance, synergism and selectivity. Trends Biotechnol, 2004, 22: 570–576
Knowles DJC, Foloppe N, Matassova NB, Murchie AIH. The bacterial ribosome, a promising focus for structure-based drug design. Curr Opin Pharmacol, 2002, 2: 501–506
Vicens Q, Westhof E. RNA as a drug target: the case of aminoglycosides. ChemBioChem, 2003, 4:1018–1023
Schmeing TM, Voorhees RM, Kelley AC, Gao YG, Murphy FV, Weir JR, Ramakrishnan V. The crystal structure of the ribosome bound to EF-Tu andaminoacyl-tRNA. Science, 2009, 326: 688–694
Moazed D, Noller HF. Interaction of antibiotics with functional sites in 16S ribosomal RNA. Nature, 1987, 327: 389–394
Purohit P, Stern S. Interactions of a small RNA with antibiotics and RNA ligands of the 30S subunit. Nature, 1994, 370: 659–662
Miyaguchi H, Narita H, Sakamoto K, Yokoyama S. An antibiotic-binding motif of an RNA fragment derived from the A-site related region of Escherichia coli 16S RNA. Nucleic Acids Res, 1996, 24: 3700–3706
Recht MI, Fourmy D, Blanchard SC, Dahlquist KD, Puglisi JD. RNA sequence determinants for aminogly-glycosides. J Mol Biol, 1996, 262: 421–436
Blanchard SC, Fourmy D, Eason RG, Puglisi JD. rRNA chemical groups required for aminoglycoside binding. Biochemistry, 1998, 37: 7716–7724
Vicens Q, Westhof E. Crystal structure of geneticin bound to a bacterial 16S ribosomal RNA A site oligonucleotide. J Mol Biol, 2003, 326: 1175–1188
Russell RJ, Murray JB, Lentzen G, Haddad J, Mobashery S. The complex of a designer antibiotic with a model aminoacyl site of the 30S ribosomal subunit revealed by X-ray crystallography. J Am Chem Soc, 2003, 125: 3410–3411
Francois B, Szychowski J, Adhikari SS, Pachamuthu K, Swayze EE, Griffey RH, Migawa MT, Westhof E, Hanessian S. Anti-bacterial aminoglycosides with a modified mode of binding to the ribosomal-RNA decoding site. Angew Chem Int Ed Engl, 2004, 43: 6735–6738
Vourloumis D, Winters GC, Simonsen KB, Takahashi M, Ayida BK, Shandrick S, Zhao Q, Han Q, Hermann T. Aminoglycoside-hybrid ligands targeting the ribosomal decoding site. ChemBioChem, 2005, 6: 58–65
Rodnina MV, Wintermeyer W. Peptide bond formation on the ribosome: Structure and mechanism. Curr Opin Struct Biol, 2003, 13: 334–340
Barbachyn MR, Ford CW. Oxazolidinone structure-activity relationships leading to linezolid. Angew ChemInt Ed Engl, 2003, 42: 2010–2023.
Zhou CC, Swaney SM, Shinabarger DL, Stockman BJ. 1H nuclear magnetic resonance study of oxazolidinone binding to bacterial ribosomes. Antimicrob Agents Chemother, 2002, 46: 625–629
Harms JM, Bartels H, Schlunzen F, Yonath A. Antibiotics acting on the translational machinery. J Cell Sci, 2003, 116: 1391–1393
Hansen JL, Moore PB, Steitz TA. Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit. J Mol Biol, 2003, 330: 1061–1075
Harms JM, Schlunzen F, Fucini P, Bartels H, Yonath A. Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin, BMC Biol, 2004, 2: 4–4
Hansen JL, Ippolito JA, Ban N, Nissen P, Moore PB, Steitz TA. The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol Cell, 2002, 10: 117–128
Schluenzen F, Harms JM, Franceschi F, Hansen HA, Bartels H, Zarivach R, Yonath A. Structural basis for the antibiotic activity of ketolides and azalides. Structure, 2003, 11: 329–338
Berisio R, Harms J, Schluenzen F, Zarivach R, Hansen HA, Fucini P, Yonath A. Structural insight into the antibiotic action of telithromycin against resistant mutants. J Bacteriol, 2003, 185: 4276–4279
Berisio R, Schluenzen F, Harms J, Bashan A, Auerbach T, Baram D, Yonath A. Structural insight into the role of the ribosomal tunnel in cellular regulation. Nat Struct Biol, 2003, 10: 366–370
Hansen JL, Ippolito JA, Ban N, Nissen P, Moore PB, Steitz TA. The structures of four macrolide antibiotics bound to the large ribosomal subunitt. Mol Cell, 2002, 10: 117–128
Liu LF. DNA topoisomerase poisons as antitumor drugs. Ann Rev Biochem, 1989: 58: 351–375
Corbett KD, Berger JM. Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases. Annu Rev Biophys Biomol Struct, 2004, 33: 95–118
Nitiss, JL. DNA topoisomerases in cancer chemotherapy: Using enzymes to generate selective DNA damage. Curr Opin Investig Drugs, 2002, 3: 1512–1516
Drlica K, Malik M, Kerns RJ, Zhao X. Quinolonemediated bacterial death. Antimicrob Agents Chemother, 2008, 52: 385–392
Forterre P, Gribaldo S, Gadelle D, Serre M C. Origin and evolution of DNA topoisomerases. Biochimie, 2007, 427-446
Lopez CR, Yang S, Deibler RW, Ray SA, Pennington JM, Digate RJ, Hastings PJ, Rosenberg SM, Zechiedrich EL. A role for topoisomerase III in a recombination pathway alternative to RuvABC. Mol Microbiol, 2005, 58: 80–101
Tabary X, Moreau N, Dureuil C, Le Goffic F. Effect of DNA gyrase inhibitors pefloxacin, five other quinolones, novobiocin, and clorobiocin on Escherichia coli topoisomerase I. Antimicrob Agents Chemother, 1987, 31: 1925–1928
Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB, Stewart L. The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc Natl Acad Sci USA, 2002, 99(24): 15387–15392
Chrencik JE, Burgin AB, Pommier Y, Stewart L, Redinbo MR. Structural impact of the leukemia drug 1-β-d-Arabinofuranosyt-osine (Ara-C) on the covalent human topoisomerase I-DNA complex. J Biol Chem, 2003, 278(14): 12461–12466
Bergerat A, Gadelle D, Forterre P. Purification of a DNA topoisomerase II from the hyperthermophilic archaeon Sulfolobus sh tures. J Biol Chem, 1994, 269: 27663–27669
Bergerat A, De Massy B, Gadelle D, Varoutas PC, Nicolas A, Forterre P. An atypical topoisomerase II from archaea with implications for meiotic recombination. Nature, 1999, 386: 414–417
Coates WJ. et al. Preparation of piperidinylalkylquinolines as antibacterials. European Patent, 1999, 051413
Wiener JJ, Gomez L, Venkatesan H, Santillán A Jr, Allison BD, Schwarz KL, Shinde S, Tang L, Hack MD, Morrow BJ, Motley ST, Goldschmidt RM, Shaw KJ, Jones TK, Grice CA. Tetrahydroindazole inhibitors of bacterial type II topoisomerases. Part 2: SAR development and potency against multidrugresistant strains. Bioorg Med Chem Lett, 2007, 7: 2718–2722
Black MT, Stachyra T, Platel D, Girard AM, Claudon M, Bruneau JM, Miossec C. Mechanism of action of the antibiotic NXL101, a novel nonfluoroquinolone inhibitor of bacterial type II topoisomerases. Antimicrob Agents Chemother, 2008, 52: 3339–3349
Bax BD, Chan PF, Eggleston DS, Fosberry A, Gentry DR, Gorrec F, Giordano L, Hann MM, Hennessy A, Hibbs M, Huang JZ, Jones E, Jones J, Brown KK, Lewis CJ, May EW, Saunders MR, Singh O, Spitzfaden CE, Shen C, XShillings A, Theobald AJ, Wohlkonig A, Pearson ND, Gwynn MN. Type IIA topoisomerase inhibition by a new class of antibacterial agents, Nature, 2010, 466: 935–939
Sheng J, Huang Z. Selenium derivatization of nucleic acids for X-ray crystal structure and function studies. Chem Biodiver, 2010, 7: 753–785
Sheng J, Salon J, Gan J-H, Huang Z. Synthesis and crystal structure study of 2′-Se-adenosine-derivatized DNA. Sci China Chem, 2010, 53: 78–85
Hassan AEA, Sheng J, Zhang W, Huang Z. High fidelity of base paring by 2-selenothymidine in DNA. J Am Chem Soc, 2010, 132: 2120–2121
Salon J, Jiang J, Sheng J, Gerlits OO, Huang Z. Derivatization of DNAs with selenium at 6-position of guanine for function and crystal structure studies. Nucleic Acids Res, 2008, 36: 7009–7018
Caton-Williams J, Huang Z. Synthesis and DNA polymerase incorporation of colored 4-selenothymidine triphosphate with a single atom substitution. Angew Chem Int Ed Engl, 2008, 47: 1723–1725
Salon J, Sheng J, Gan J-H, Huang Z. Synthesis and crystal structure of 2′-Se-modified guanosine containing DNA. J Org Chem, 2010, 75: 637–641
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Gan, J., Sheng, J. & Huang, Z. Chemical and structural biology of nucleic acids and protein-nucleic acid complexes for novel drug discovery. Sci. China Chem. 54, 3–23 (2011). https://doi.org/10.1007/s11426-010-4174-x
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DOI: https://doi.org/10.1007/s11426-010-4174-x