Targeting RNA: New opportunities to address drugless targets

Drug Discovery Today

Volumn 8, Issue 7, 2003, Pages 297-306

  Zaman, Guido J R ^a   Michiels, Paul J A ^a   Van Boeckel, Constant A A ^a  

^a NV ORGANON   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOGLYCOSIDE ANTIBIOTIC AGENT; BACTERIAL RNA; MESSENGER RNA; PROTEIN; RIBOSOME RNA; RNA; VIRUS RNA;

CLINICAL MEDICINE; DRUG INDUSTRY; DRUG TARGETING; GENE CONTROL; GENE TARGETING; GENETIC CODE; GENETIC DISORDER; REVIEW; RNA SEQUENCE; SPERMATOGENESIS;

AMINOGLYCOSIDES; ANIMALS; ANTI-BACTERIAL AGENTS; BINDING SITES; DRUG DESIGN; GENE EXPRESSION REGULATION; HUMANS; NUCLEIC ACID CONFORMATION; RNA; RNA, BACTERIAL; RNA, MESSENGER; RNA, RIBOSOMAL; RNA, VIRAL; RNA-BINDING PROTEINS;

EID: 0037376594     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1359-6446(03)02624-2     Document Type: Review

References (62)

1. Drews J. Drug discovery: a historical perspective. Science. 287:2000;1960-1964.
2. Venter J.C., et al. The sequence of the human genome. Science. 291:2001;1304-1351.
3. Fox S.J., et al. High-throughput screening 2002: moving toward increased success rates. J. Biomol. Screen. 7:2002;313-316.
4. Ecker D.J., Griffey R.H. RNA as a small-molecule drug target: doubling the value of genomics. Drug Discov. Today. 4:1999;420-429.
5. Wilson W.D., Li K. Targeting RNA with small molecules. Curr. Med. Chem. 7:2000;73-98.
6. Xavier K.A., et al. RNA as a drug target: methods for biophysical characterization and screening. Trends Biotechnol. 18:2000;349-356.
7. Fourmy D., et al. Structure of the A-site of E. coli 16S ribosomal RNA complexed with an aminoglycoside antibiotic. Science. 274:1996;1367-1371.
8. Wong C-H., et al. A library approach to the discovery of small molecules that recognize RNA: use of a 1,3-hydroxyamine motif as core. J. Am. Chem. Soc. 120:1998;8319-8327.
9. Griffey R.H., et al. Determinants of aminoglycoside-binding specificity for rRNA by using mass spectrometry. Proc. Natl. Acad. Sci. U. S. A. 96:1999;10129-10133.
10. Carter A.P., et al. Functional insights from the structure of the 30S ribosomal subunit and its interaction with antibiotics. Nature. 407:2000;340-348.
11. Davis B.D., et al. Misread protein creates membrane channels: An essential step in the bactericidal action of aminoglycosides. Proc. Natl. Acad. Sci. U. S. A. 83:1986;6164-6168.
12. Cundliffe E. How antibiotic-producing organisms avoid suicide. Annu Rev. Microbiol. 43:1989;207-233.
13. De Stasio E.A., et al. Mutations in 16S ribosomal RNA disrupt antibiotic - RNA interactions. EMBO J. 8:1989;1213-1216.
14. Wang Y., et al. Specificity of aminoglycoside binding to RNA constructs derived from the 16S rRNA decoding region and the HIV-RRE activator region. Biochemistry. 36:1997;768-779.
15. Ryu D.H., Rando R.R. Aminoglycoside binding to human and bacterial A-site rRNA decoding region constructs. Bioorg. Med. Chem. 9:2001;2601-2608.
16. Hamasaki K., Rando R.R. Specific binding of aminoglycosides to human rRNA construct based on a DNA polymorphism which causes aminoglycoside-induced deafness. Biochemistry. 36:1997;12323-12328.
17. Ryu D.H., Rando R.R. Decoding region bubble size and aminoglycoside antibiotic binding. Bioorg. Med. Chem. Lett. 12:2002;2241-2244.
18. Hutchin T., Cortopassi G. Proposed molecular and cellular mechanism for aminoglycoside ototoxicity. Antimicrob. Agents Chemother. 38:1994;2517-2520.
19. Recht M.I., et al. Basis for prokaryotic specificity of action of aminoglycoside antibiotics. EMBO J. 18:1999;3133-3138.
20. Schmitz C., et al. Megalin deficiency offers protection from renal aminoglycoside accumulation. J. Biol. Chem. 277:2002;618-622.
21. Dutton, G. (2000) Biotech counters bioterrorism. Gen. Engineering 20, No. 21, December 2000.
22. Howard M.B., et al. Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations. Nat. Med. 2:1996;467-469.
23. Bedwell D.M., et al. Suppression of a CFTR premature stop mutation in a bronchial epithelial cell line. Nat. Med. 3:1997;1280-1284.
24. Clancy J.P., et al. Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis. Am. J. Respir. Crit. Care Med. 163:2001;1683-1692.
25. Barton-Davis E.R., et al. Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. J. Clin. Invest. 104:1999;375-381.
26. Keeling K.M., et al. Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of α-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation. Hum. Mol. Genet. 10:2001;291-299.
27. Investigational Drugs Database available online at http://www.current-drugs.com.
28. Manuvakhova M., et al. Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translation system. RNA. 6:2000;1044-1055.
29. Zapp M.L., et al. Small molecules that selectively block RNA binding of HIV-1 Rev protein inhibit Rev function and viral production. Cell. 74:1993;969-978.
30. Mei H-Y., et al. Inhibition of an HIV-1 Tat-derived peptide binding to TAR RNA by aminoglycoside antibiotics. Bioorg. Med. Chem. Lett. 5:1995;2755-2760.
31. Mei H.Y., et al. Inhibitors of protein-RNA complexation that target the RNA: Specific recognition of human immunodeficiency virus type 1 TAR RNA by small organic molecules. Biochemistry. 37:1998;14204-14212.
32. Hwang S., et al. Inhibition of gene expression in human cells through small molecule-RNA interactions. Proc. Natl. Acad. Sci. U. S. A. 96:1999;12997-13002.
33. Theil E.C. Targeting mRNA to regulate iron and oxygen metabolism. Biochem. Pharmacol. 59:2000;87-93.
34. Rogers J.T., et al. An iron-responsive element type II in the 5·-untranslated region of the Alzheimer's amyloid precursor protein transcript. J. Biol. Chem. 277:2002;45518-45528.
35. Rogers J.T., et al. Alzheimer's disease drug discovery targeted to the APP mRNA 5′ untranslated region. J. Mol. Neurosci. 19:2002;77-82.
36. Tok J.B-H., et al. Aminoglycoside antibiotics are able to specifically bind the 5′-untranslated region of thymidylate synthase messenger RNA. Biochemistry. 38:1999;199-206.
37. Ekblom J. IRESes: New potential drug targets. Drug Discov. Today. 6:2001;1259-1260.
38. Chappell S.A., et al. A mutation in the c-myc-IRES leads to enhanced internal ribosome entry in multiple myeloma: a novel mechanism of oncogene deregulation. Oncogene. 19:2000;4437-4440.
39. Elliott D.J., Cooke H.J. The molecular genetics of male infertility. Bioessays. 19:1997;801-809.
40. Ruggiu M., et al. The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature. 389:1997;73-77.
41. Eberhart C.G., et al. Meiotic cell cycle requirement for a fly homologue of human deleted in azoospermia. Nature. 381:1996;783-785.
42. Slee R., et al. A human DAZ transgene confers partial rescue of the mouse Dazl null phenotype. Proc. Natl. Acad. Sci. U. S. A. 96:1999;8040-8045.
43. Jiao X., et al. Identification of target messenger RNA substrates for the murine deleted in azoospermia-like RNA-binding protein. Biol. Reprod. 66:2002;475-485.
44. Gatignol A., et al. Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR. Science. 251:1991;1597-1600.
45. Siffroi J.P., et al. Expression of the TAR RNA binding protein in human testis. Mol. Hum. Reprod. 7:2001;219-225.
46. Lee K., et al. A testis cytoplasmic RNA-binding protein that has the properties of a translational repressor. Mol. Cell. Biol. 16:1996;3023-3034.
47. Fajardo M.A., et al. Separate elements in the 3′ untranslated region of the mouse Protamine 1 mRNA regulate translational repression and activation during murine spermatogenesis. Dev. Biol. 191:1997;42-52.
48. Zhong J., et al. A double-stranded RNA binding protein required for activation of repressed messages in mammalian germ cells. Nat. Genet. 22:1999;171-174.
49. Pérez-Cañadillas J-M., Varani G. Recent advances in RNA-protein recognition. Curr. Opin. Struct. Biol. 11:2001;53-58.
50. Zuker M., Stiegler P. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. 9:1981;133-148.
51. Moore P.B. Structural motifs in RNA. Annu. Rev. Biochem. 68:1999;287-300.
52. Ehresmann C., et al. Probing the structure of RNAs in solution. Nucleic Acids Res. 15:1987;9109-9128.
53. Swayze E.E., et al. SAR by MS: A ligand based technique for drug lead discovery against structured RNA targets. J. Med. Chem. 45:2002;3816-3819.
54. Pope A.J., et al. Homogeneous fluorescence readouts for miniaturized high-throughput screening: theory and practice. Drug Discov. Today. 4:1999;350-362.
55. Mei H-Y., et al. Discovery of selective, small-molecule inhibitors of RNA complexes: I. The tat protein/TAR RNA complexes required for HIV-1 transcription. Bioorg. Med. Chem. 5:1997;1173-1184.
56. Huq, I. et al. (2002) Inhibitors of HIV-1 Tat-TAR Interactions: A Bead Based Combinatorial Chemistry Approach. RNA 2002, 7th annual meeting of the RNA society, Madison, Wisconsin, U.S.A.
57. Hobson, D. et al. (2002) Targeting RNA: Novel Ways to Screen an Old Player. RNA 2002, 7th annual meeting of the RNA society, Madison, Wisconsin, U.S.A.
58. Soukup G.A., Breaker R.R. Engineering precision RNA molecular switches. Proc. Natl. Acad. Sci. U.S A. 6:1999;3584-3589.
59. Nahvi A., et al. Genetic control by a metabolite binding mRNA. Chem. Biol. 9:2002;1043-1049.
60. Winkler W., et al. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature. 419:2002;952-956.
61. Vicens Q., Westhof E. Crystal structure of paromomycin docked into the eubacterial ribosomal decoding site. Structure. 9:2001;647-658.
62. Koradi R., et al. MOLMOL: a program for display and analysis of macromolecular structures. J. Mol. Graph. 14:1996;51-55.