Identification of small molecule inhibitors of the HIV-1 Nucleocapsid-Stem-Loop 3 RNA Complex

Journal of Medicinal Chemistry

Volumn 55, Issue 9, 2012, Pages 4132-4141

  Warui, Douglas M ^a   Baranger, Anne M ^a  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRETROVIRUS AGENT; DOUBLE STRANDED RNA; LIGAND; NUCLEIC ACID; NUCLEOCAPSID PROTEIN; NUCLEOCAPSID PROTEIN 7; PSI RNA; RNA; SINGLE STRANDED RNA; STEM LOOP 3 RNA; UNCLASSIFIED DRUG; VIRUS PROTEIN;

ANIMAL CELL; ANTIVIRAL ACTIVITY; ARTICLE; BINDING AFFINITY; CHEMICAL STRUCTURE; COMPUTATIONAL FLUID DYNAMICS; CONTROLLED STUDY; DRUG SOLUBILITY; DRUG TARGETING; ENZYME INHIBITION; HIGH THROUGHPUT SCREENING; HUMAN IMMUNODEFICIENCY VIRUS 1; IC 50; MOLECULAR DOCKING; MOLECULE; NONHUMAN; PROTEIN PROTEIN INTERACTION; RNA BINDING; VIRUS NUCLEOCAPSID; VIRUS REPLICATION;

AMINO ACID SEQUENCE; ANTI-HIV AGENTS; BASE SEQUENCE; ELECTROPHORETIC MOBILITY SHIFT ASSAY; GAG GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; HIV INFECTIONS; HIV-1; HUMANS; KINETICS; LIGANDS; MOLECULAR DYNAMICS SIMULATION; MOLECULAR SEQUENCE DATA; NUCLEIC ACID CONFORMATION; PROTEIN BINDING; RNA, VIRAL;

EID: 84861016261     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2007694     Document Type: Article

References (69)

1. Brisson-Noel, A.; Trieu-Cuot, P.; Courvalin, P. Mechanism of action of spiramycin and other macrolides Chemotherapy 1988, 22 (Suppl. B) 13-23
2. Heinz, B. A.; McKinght, K. l. RNA as a target for developing antivirals Antiviral Chem. Chemother. 2003, 14, 61-73 (Pubitemid 36781666)
3. Cheng, A. C.; Calabro, V.; Frankel, A. D. Design of RNA-binding proteins and ligands Curr. Opin. Struct. Biol. 2001, 11, 478-484 (Pubitemid 32728501)
4. DeJong, E. S.; Luy, B.; Marino, J. P. RNA and RNA-protein complexes as targets for therapeutic intervention Curr. Top. Med. Chem 2002, 2, 289-302
5. Schroeder, R.; Barta, A.; Semrad, K. Strategies for RNA folding and assembly Nat. Rev. Mol. Cell Biol. 2004, 5, 908-919 (Pubitemid 39486542)
6. Sevignani, C.; Calin, G. A.; Siracusa, L. D.; Crose, C. M. Mammalian microRNAs: a small world for fine-tuning gene expression Mamm. Genome 2006, 17, 189-202 (Pubitemid 43327650)
7. Vicens, Q.; Westhof, E. RNA as a drug target: the case of aminoglycosides ChemBioChem 2003, 4, 1018-1023 (Pubitemid 37267590)
8. Winkler, W. C.; Breaker, R. R. Genetic control by metabolite-binding riboswitches ChemBioChem 2003, 4, 1024-1032 (Pubitemid 37267591)
9. Bélanger, F.; Gagnon, M. G.; Steinberg, S. V.; Cunningham, P. R.; Brakier-Gingras, L. Study of the functional interaction of the 900 tetraloop of 16S ribosomal RNA with helix 24 within the bacterial ribosome J. Mol. Biol. 2004, 338, 683-693 (Pubitemid 38507414)
10. Bozdogan, B.; Appelbaum, P. C. Oxazolidinones: activity, mode of action, and mechanism of resistance Int. J. Antimicrob. Agents 2004, 23, 113-119 (Pubitemid 38175391)
11. Brodersen, D. E.; Clemons, W. M. J.; Carter, A. P.; Morgan-Warren, R. J.; Wimberly, B. T.; Ramakrishnan, V. The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit Cell 2000, 103, 1143-1154 (Pubitemid 32037400)
12. Tor, Y. The ribosomal A-site as an inspiration for the design of RNA binders Biochimie 2006, 88, 1045-1051
13. Thomas, J. R.; Hergenrother, P. J. Targeting RNA with small molecules Chem. Rev. 2008, 108, 1171-1224 (Pubitemid 351638813)
14. Lee, M. M.; Pushechnikov, A.; Disney, M. D. Rational and modular design of potent ligands targeting the RNA that causes myotonic dystrophy 2 ACS Chem. Biol. 2009, 4, 345-355
15. Pushechnikov, A.; Lee, M. M.; Childs-Disney, J. L.; Sobczak, K.; French, J. M.; Thornton, C. A.; Disney, M. D. Rational design of ligands targeting triplet repeating transcripts that cause RNA dominant disease: application to myotonic muscular dystrophy type 1 and spinocerebellar ataxia type 3 J. Am. Chem. Soc. 2009, 131, 9767-9779
16. Lee, M. M.; Childs-Disney, J. L.; Pushechnikov, A.; French, J. M.; Sobczak, K.; Thornton, C. A.; Disney, M. D. Controlling the specificity of modularly assembled small molecules for RNA via ligand module spacing: targeting the RNAs that cause myotonic muscular dystrophy J. Am. Chem. Soc. 2009, 131, 17464-17472
17. Tibodeau, J. D.; Fox, P. M.; Ropp, P. A.; Theil, E. C.; Thorp, H. H. The up-regulation of ferritin expression using a small-molecule ligand to the native mRNA Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 253-257 (Pubitemid 43122387)
18. Kirk, S. R.; Luedtke, N. W.; Tor, Y. Neomycin-acridine conjugate: a potent inhibitor of Rev-RRE binding J. Am. Chem. Soc. 2000, 122, 980-981 (Pubitemid 30094420)
19. Gayle, A. Y.; Baranger, A. M. Inhibition of the U1A-RNA complex by an aminoacridine derivative Bioorg. Med. Chem. Lett. 2002, 12, 2839-2842 (Pubitemid 35266745)
20. Manfroni, G.; Gatto, B.; Tabarrini, O.; Sabatini, S.; Cecchetti, V.; Giaretta, G.; Parolin, C.; Vecchio, C. D.; Calistri, A.; Palumbo, M.; Fravolini, A. Synthesis and biological evaluation of 2-phenylquinolones targeted at Tat/TAR interaction Bioorg. Med. Chem. Lett. 2009, 19, 714-717
21. Gareiss, P. C.; Sobczak, K.; McNaughton, B. R.; Palde, P. B.; Thornton, C. A.; Miller, B. L. Dynamic combinatorial selection of molecules capable of inhibiting the (CUG) repeat-MBNL1 interaction in vitro: discovery of lead compounds targeting myotonic dystrophy (DM1) J. Am. Chem. Soc. 2008, 130, 16254-16261
22. Galicia-Vazquez, G.; Lindqvist, L.; Wang, X.; Harvey, I. High-throughput assays probing protein-RNA interactions of eukaryotic translation initiation factors Anal. Biochem. 2009, 384
23. Arambula, J. F.; Ramisetty, R. R.; Baranger, A. M.; Zimmerman, S. C. A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 16068-16073
24. Warf, M. B.; Nakamori, M.; Matthys, C. M.; Thornton, C. A.; Berglund, J. A. Pentamidine reverses the splicing defects associated with myotonic dystrophy Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 18551-18556
25. Wang, D.; Iera, J.; Baker, H.; Hogan, P.; Ptak, R.; Yang, L.; Hartman, T.; Buckheit, R. W.; Desjardins, A.; Yang, A.; Legault, P.; Yedavalli, V.; Jeang, K.-T.; Apella, D. H. Multivalent binding oligomers inhibit HIV Tat-TAR interaction critical for viral replication Bioorg. Med. Chem. 2009, 19, 6893-6897
26. Xiao, G.; Kumar, A.; Li, K.; Rigle, C. T.; Bajic, M.; Davis, T. M.; Boykin, D. W.; Wilson, W. D. Inhibition of the HIV-1 Rev-RRE complex formation by unfused aromatic cations Bioorg. Med. Chem. 2001, 9, 1097-1113 (Pubitemid 32453270)
27. Schirle, N. T.; Goodman, R. A.; Krishnamurthy, M.; Beal, P. A. Selective inhibition of ADAR2-catalyzed editing of the serotonin 2c receptor pre-mRNA by a helix-threading peptide Org. Biomol. Chem. 2010, 8, 4898-4904
28. Bugaut, A.; Rodriguez, R.; Kumari, S.; Hsu, D. S.-T.; Balasubramanian, S. Small molecule-mediated inhibition of translation by targeting a native RNA G-quadruplex Org. Biomol. Chem. 2010, 8, 2771-2776
29. Gatto, B.; Tabarrini, O.; Massari, S.; Giaretta, G.; Sabatini, S.; Vecchio, C. D.; Parolin, C.; Fravolini, A.; Palumbo, M.; Cecchetti, V. 2-Phenylquinolones as inhibitors of the HIV-1 Tat-TAR interaction ChemMedChem 2009, 4, 935-938
30. Turner, K. B.; Hagan, N. A.; Fabris, D. Inhibitory effects of archetypical nucleic acid ligands on the interactions of HIV-1 nucleocapsid protein with elements of psi-RNA Nucleic Acids Res. 2006, 34, 1305-1316
31. Amarasinghe, G. K.; De Guzman, R. N.; Turner, R. B.; Chancellor, K. J.; Wu, Z. R.; Summers, M. F. NMR structure of the HIV-1 nucleocapsid protein bound to stem-loop SL2 of the Psi-RNA packaging signal. Implications for genome recognition J. Mol. Biol. 2000, 301, 491-511
32. Darlix, E.-L.; Lapadat-Tapolsky, M.; Rocquigny, H. D.; Roques, B. P. First glimpses at structure-function relationships of the nucleocapsid protein of retroviruses J. Mol. Biol. 1995, 254, 523-537 (Pubitemid 26001788)
33. Dietz, J. K., J.; Kaur, A.; Raja, C.; Stein, S.; Grez, M.; Pustowka, A.; Mensch, S.; Ferner, J.; Möller, L.; Bannert, N.; Tampé, R.; Divita, G.; Mély, Y.; Schwalbe, H.; Dietrich, U. Inhibition of HIV-1 by a peptide ligand of the genomic RNA packaging signal psi ChemMedChem 2008, 3, 749-755
34. Chadwick, D. R.; Lever, A. M. Antisense RNA sequences targeting the 5 leader packaging signal region of human immunodeficiency virus type-1 inhibits viral replication at post-transcriptional stages of the life cycle Gene Ther. 2000, 7, 1362-1368 (Pubitemid 30662241)
35. Clever, J.; Sassetti, C.; Parslow, T. G. RNA secondary structure and binding sites for gag gene products in the 5 packaging signal of human immunodeficiency virus type 1 J. Virol. 1995, 69, 2101-2109
36. Clever, J. L.; Eckstein, D. A.; Parslow, T. G. Genetic dissociation of the encapsidation and reverse transcription functions in the 5 R region of human immunodeficiency virus type 1 J. Virol. 1999, 73, 101-109 (Pubitemid 28565351)
37. Clever, J. L.; Parslow, T. G. Mutant human immunodeficiency virus type 1 genomes with defects in RNA dimerization or encapsidation J. Virol. 1997, 71, 3407-3414 (Pubitemid 27172349)
38. Damgaard, C. K.; Dyhr-Mikkelsen, H.; Kjems, J. Mapping the RNA binding sites for human immunodeficiency virus type-1 Gag and NC proteins within the complete HIV-1 and -2 untranslated leader regions Nucleic Acids Res. 1998, 26, 3667-3676 (Pubitemid 28367971)
39. Hayashi, T.; Shioda, T.; Iwakura, Y.; Shibuta, H. RNA packaging signal of human immunodeficiency virus type 1 Virology 1992, 188, 590-599
40. McBride, M. S.; Panganiban, A. T. The human immunodeficiency virus type 1 encapsidation site is a multipartite RNA element composed of functional hairpin structures J. Virol. 1996, 70, 2963-2973 (Pubitemid 26121910)
41. McBride, M. S.; Panganiban, A. T. Position dependence of functional hairpins important for human immunodeficiency virus type 1 RNA encapsidation in vivo J. Virol. 1997, 71, 2050-2058 (Pubitemid 27078583)
42. McBride, M. S.; Schwartz, M. D.; Panganiban, A. T. Efficient encapsidation of human immunodeficiency virus type 1 vectors and further characterization of cis elements required for encapsidation J. Virol. 1997, 71, 4544-4554 (Pubitemid 27204147)
43. Michael, F. S.; Andrew, C. P.; Bruce, S. H.; Philip, N. B. Affinities of packaging domain loops in HIV-1 RNA for the nucleocapsid protein Biochemistry 2002, 41, 5276-5282
44. Dorman, M. N.; Lever, A. M. L. Investigation of RNA transcripts containing HIV-1 packaging signal sequences as HIV-1 antivirals: generation of cell lines resistant to HIV-1 Gene Ther. 2001, 8, 157-165 (Pubitemid 32162429)
45. Jenkins, L. M. M.; Byrd, J. C.; Hara, T.; Srivastava, P.; Mazur, S. J.; Stahl, S. J.; Inman, J. K.; Appella, E.; Omichinski, J. G.; Legault, P. Studies on the mechanism of inactivation of the HIV-1 nucleocapsid protein NCp7 with 2-mercaptobenzamide thioesters J. Med. Chem. 2005, 48, 2847-2858 (Pubitemid 40548099)
46. Paillart, J.-C.; Shehu-Xhilaga, M.; Marquet, R.; Mak, J. Dimerization of retroviral RNA genomes: an inseparable pair Nat. Rev. Microbiol. 2004, 2, 461-472 (Pubitemid 39200013)
47. Rice, W. G.; Supko, J. G.; Malspeis, L.; Buckheit, R. W.; Clanton, D.; Bu, M.; Graham, L.; Schaeffer, C. A.; Turpin, J. A.; Domagala, J.; Gogliotti, R.; Bader, J. P.; Halliday, S. M.; Coren, L.; Sowder, R. C.; Arthur, L. O.; Henderson, L. E. Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the treatment of AIDS Science 1995, 270, 1194-1197
48. Skripkin, E.; Paillart, J.-C.; Marquet, R.; Blumenfeld, M.; Ehresmann, B.; Ehresmann, C. Mechanisms of inhibition of in vitro dimerization of HIV type I RNA by sense and antisense oligonucleotides J. Biol. Chem. 1996, 271, 28812-28817 (Pubitemid 26382578)
49. Warui, D. M.; Baranger, A. M. Identification of specific small molecule ligands for stem loop 3 ribonucleic acid of the packaging signal psi of human immunodeficiency virus-I J. Med. Chem. 2009, 52, 5462-5473
50. Yan, Z.; Sikri, S.; Beveridge, D. L.; Baranger, A. M. Identification of an aminoacridine derivative that binds to RNA tetraloops J. Med. Chem. 2007, 50, 4096-4104 (Pubitemid 47301741)
51. Haddad, J.; Kotra, L. P.; Liano-Sotelo, B.; Kim, C.; Azucena, E. F.; Liu, M.; Vakulenko, S. B.; Chow, C. S.; Mobashery, S. Design of novel antibiotics that bind to the ribosomal acyltransfer site J. Am. Chem. Soc. 2002, 124, 3229-3237 (Pubitemid 34270361)
52. Barbault, F.; Zhang, L.; Zhang, L.; Fan, B. T. Parametrization of a specific free energy function for automated docking against RNA targets using neural networks Chem. Intell. Lab. Syst. 2006, 82, 269-275
53. Chen, Q.; Kuntz, I. D.; Shafer, R. H. Structure-Based Design of Nucleic Acid Binding Drugs. In Structure, Motion, Interaction and Expression of Biological Macromolecules; Adenine Press: New York, 1997; pp 227-231.
54. Detering, C.; Varani, G. Validation of automated docking programs for docking and database screening against RNA drug targets J. Med. Chem. 2004, 47, 4188-4201 (Pubitemid 39045426)
55. Evans, D. A.; Neidle, S. Virtual screening of DNA minor groove binders J. Med. Chem. 2006, 49, 4232-4238 (Pubitemid 44036666)
56. Moitessier, N.; Westhof, E.; Hanessian, S. Docking of aminoglycosides to hydrated and flexible RNA J. Med. Chem. 2006, 49, 1023-1033 (Pubitemid 43221650)
57. Zhang, X.; Wang, X.; Liu, C. Molecular docking and 3D-QSAR study of pyranmycin derivatives against 16S rRNA A site J. Mol. Struct.: THEOCHEM 2005, 730, 85-94 (Pubitemid 41420921)
58. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function J. Comput. Chem. 1998, 19, 1639-1662 (Pubitemid 128590223)
59. De Guzman, R. N.; Wu, Z. R.; Stalling, C. C.; Pappalardo, L.; Borer, P. N.; Summers, M. F. Structure of the HIV-1 nucleocapsid protein bound to the SL3 psi-RNA recognition element Science 1998, 249, 384-388 (Pubitemid 28063374)
60. Liu, X.; Thomas, J. R.; Hergenrother, P. J. Deoxystreptamine dimers bind to RNA hairpin loops J. Am. Chem. Soc. 2004, 126, 9196-9197 (Pubitemid 38989433)
61. Thomas, J. R.; Liu, X.; Hergenrother, P. J. Size-specific ligands for RNA hairpin loops J. Am. Chem. Soc. 2005, 127, 12434-12435 (Pubitemid 41292130)
62. Ramisetty, S. R.; Baranger, A. M. Cooperative binding of a quinoline derivative to an RNA stem loop containing a dangling end Bioorg. Med. Chem. Lett. 2010, 20, 3134-3137
63. Shen, L. L.; Mitscher, L. A.; Sharma, P. N.; O'Donnell, T. J.; Chu, D. W. T.; Cooper, C. S.; Rosen, T.; Pernet, A. G. Mechanism of inhibition of DNA gyrase by quinolone antibacterials: a cooperative drug-DNA binding model Biochemistry 1989, 28, 3886-3894 (Pubitemid 19125438)
64. Kwon, M.; Strobel, S. A. Chemical basis of glycine riboswitch cooperativity RNA 2008, 14, 25-34
65. Mandal, M.; Lee, M.; Barrick, J. E.; Weinberg, Z.; Emilsson, G. M.; Ruzzo, W. L.; Breaker, R. R. A glycine-dependent riboswitch that uses cooperative binding to control gene expression Science 2004, 306, 275-279 (Pubitemid 39336872)
66. Llano-Sotelo, B.; Azucena, E.; Kotra, L.; Mobashery, S.; Chow, C. Aminoglycosides modified by resistance enzymes display diminished binding to the bacterial ribosomal aminoacyl-tRNA site Chem. Biol. 2002, 9, 455-463 (Pubitemid 34439764)
67. Llano-Sotelo, B.; Chow, C. S. RNA-aminoglycoside antibiotic interactions: fluorescence detection of binding and conformational change Bioorg. Med. Chem. Lett. 1999, 8, 213-216 (Pubitemid 29059531)
68. Carteau, S. G.; R., J.; Bushman, F. D. Coupled integration of human immunodeficiency virus type 1 cDNA ends by purified integrase in vitro: stimulation by the viral nucleocapsid protein J. Virol. 1999, 73, 6670-6679 (Pubitemid 29327849)
69. Stewart-Maynard, K. M.; Cruceanu, M.; Wang, F.; Vo, M.-N.; Gorelick, R. J.; Williams, M. C.; Rouzina, I.; Musier-Forsyth, K. Retroviral nucleocapsid proteins display nonequivalent levels of nucleic acid chaperone activity J. Virol. 2008, 82, 10129-10142