Structural and binding analysis of pyrimidinol carboxylic acid and N-hydroxy quinazolinedione HIV-1 RNase H inhibitors

Antimicrobial Agents and Chemotherapy

Volumn 55, Issue 6, 2011, Pages 2905-2915

  Lansdon, Eric B ^a   Liu, Qi ^a   Leavitt, Stephanie A ^a   Balakrishnan, Mini ^a   Perry, Jason K ^a   Lancaster Moyer, Candra ^a   Kutty, Nilima ^a,b   Liu, Xiaohong ^a   Squires, Neil H ^a   Watkins, William J ^a   Kirschberg, Thorsten A ^a  

^a GILEAD SCIENCES   (United States)

^b JAZZ PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CARBOXYLIC ACID DERIVATIVE; ESCHERICHIA COLI PROTEIN; INTEGRASE; MAGNESIUM ION; MANGANESE; N HYDROXY QUINAZOLINEDIONE DERIVATIVE; PHOSPHODIESTERASE; QUINAZOLINE DERIVATIVE; RALTEGRAVIR; RIBONUCLEASE H; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ARTICLE; CATALYSIS; CRYSTAL STRUCTURE; DNA RNA HYBRIDIZATION; DRUG PROTEIN BINDING; ENZYME ACTIVE SITE; ENZYME ANALYSIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; METAL BINDING; NONHUMAN; PHARMACOPHORE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVERSE TRANSCRIPTION; SEQUENCE ANALYSIS; STRUCTURE ANALYSIS; SURFACE PLASMON RESONANCE; VIRUS REPLICATION;

AMINO ACID SEQUENCE; ANTI-HIV AGENTS; CRYSTALLIZATION; HIV REVERSE TRANSCRIPTASE; HIV-1; MOLECULAR CONFORMATION; MOLECULAR SEQUENCE DATA; PYRIMIDINES; QUINAZOLINONES; RIBONUCLEASE H; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79956334444     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01594-10     Document Type: Article

References (61)

1. Adams, P. D., et al. 2010. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66:213-221.
2. Andreola, M. L., et al. 2002. HIV-1 integrase and RNase H activities as therapeutic targets. Expert Opin. Ther. Targets 6:433-446.
3. Arts, E. J., and S. F. Le Grice. 1998. Interaction of retroviral reverse transcriptase with template-primer duplexes during replication. Prog. Nucleic Acid Res. Mol. Biol. 58:339-393.
4. Billamboz, M., et al. 2008. Design, synthesis, and biological evaluation of a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones as dual inhibitors of human immunodeficiency virus type 1 integrase and the reverse transcriptase RNase H domain. J. Med. Chem. 51:7717-7730.
5. Bohlayer, W. P., and J. J. DeStefano. 2006. Tighter binding of HIV reverse transcriptase to RNA-DNA versus DNA-DNA results mostly from interactions in the polymerase domain and requires just a small stretch of RNA-DNA. Biochemistry 45:7628-7638.
6. Bokesch, H. R., et al. 2008. HIV-1 ribonuclease H inhibitory phenolic glycosides from Eugenia hyemalis. J. Nat. Prod. 71:1634-1636.
7. Borkow, G., et al. 1997. Inhibition of the ribonuclease H and DNA polymerase activities of HIV-1 reverse transcriptase by N-(4-tert-butylbenzoyl)- 2-hydroxy-1-naphthaldehyde hydrazone. Biochemistry 36:3179-3185. (Pubitemid 27142389)
8. Budihas, S. R., et al. 2005. Selective inhibition of HIV-1 reverse transcriptase- associated ribonuclease H activity by hydroxylated tropolones. Nucleic Acids Res. 33:1249-1256. (Pubitemid 41439918)
9. Champoux, J. J. 1993. Reverse transcriptase, p. 103-117. In A. M. Skalka and S. P. Goff (ed.), Reverse transcriptase. Cold Spring Harbor Laboratory Press, Plainview, NY.
10. Chung, S., et al. 2010. Structure-activity analysis of vinylogous urea inhibitors of human immunodeficiency virus-encoded ribonuclease H. Antimicrob. Agents Chemother. 54:3913-3921.
11. Cirino, N. M., et al. 1995. Divalent cation modulation of the ribonuclease functions of human immunodeficiency virus reverse transcriptase. Biochemistry 34:9936-9943.
12. Cowan, J. A., et al. 2000. Metal-ion stoichiometry of the HIV-1 RT ribonuclease H domain: evidence for two mutually exclusive sites leads to new mechanistic insights on metal-mediated hydrolysis in nucleic acid biochemistry. J. Biol. Inorg. Chem. 5:67-74.
13. Dat, N. T., et al. 2007. A dimeric lactone from Ardisia japonica with inhibitory activity for HIV-1 and HIV-2 ribonuclease H. J. Nat. Prod. 70:839-841.
14. Emsley, P., and K. Cowtan. 2004. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60:2126-2132.
15. Evans, D. B., K. Brawn, M. R. Deibel, Jr., W. G. Tarpley, and S. K. Sharma. 1991. A recombinant ribonuclease H domain of HIV-1 reverse transcriptase that is enzymatically active. J. Biol. Chem. 266:20583-20585.
16. Goody, R. S., B. Muller, and T. Restle. 1991. Factors contributing to the inhibition of HIV reverse transcriptase by chain-terminating nucleotides in vitro and in vivo. FEBS Lett. 291:1-5.
17. Halgren, T. 2007. New method for fast and accurate binding-site identification and analysis. Chem. Biol. Drug Des. 69:146-148.
18. Hang, J. Q., et al. 2004. Activity of the isolated HIV RNase H domain and specific inhibition by N-hydroxyimides. Biochem. Biophys. Res. Comm. 317:321-329.
19. Harding, M. M. 2001. Geometry of metal-ligand interactions in proteins. Acta Crystallogr. D Biol. Crystallogr. 57:401-411.
20. Harding, M. M. 1999. The geometry of metal-ligand interactions relevant to proteins. Acta Crystallogr. D Biol. Crystallogr. 55:1432-1443.
21. Hare, S., S. S. Gupta, E. Valkov, A. Engelman, and P. Cherepanov. 2010. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature 464:232-236.
22. Haren, L., B. Ton-Hoang, and M. Chandler. 1999. Integrating DNA: transposases and retroviral integrases. Annu. Rev. Microbiol. 53:245-281.
23. Himmel, D. M., et al. 2009. Structure of HIV-1 reverse transcriptase with the inhibitor beta-thujaplicinol bound at the RNase H active site. Structure 17:1625-1635.
24. Huang, H., R. Chopra, G. L. Verdine, and S. C. Harrison. 1998. Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 282:1669-1675.
25. Jones, T. A., J. Y. Zou, S. W. Cowan, and M. Kjeldgaard. 1991. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47(Pt. 2):110-119.
26. Keck, J. L., and S. Marqusee. 1995. Substitution of a highly basic helix/loop sequence into the RNase H domain of human immunodeficiency virus reverse transcriptase restores its Mn(2+)-dependent RNase H activity. Proc. Natl. Acad. Sci. U. S. A. 92:2740-2744.
27. Kirschberg, T. A., et al. 2009. RNase H active site inhibitors of human immunodeficiency virus type 1 reverse transcriptase: design, biochemical activity, and structural information. J. Med. Chem. 52:5781-5784.
28. Klumpp, K., et al. 2003. Two-metal ion mechanism of RNA cleavage by HIV RNase H and mechanism-based design of selective HIV RNase H inhibitors. Nucleic Acids Res. 31:6852-6859. (Pubitemid 37508792)
29. Klumpp, K., and T. Mirzadegan. 2006. Recent progress in the design of small molecule inhibitors of HIV RNase H. Curr. Pharm. Des. 12:1909-1922.
30. Koch, U., et al. 2006. 2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as inhibitors of the hepatitis C virus NS5B polymerase: discovery, SAR, modeling, and mutagenesis. J. Med. Chem. 49:1693-1705.
31. Lansdon, E. B., et al. 2010. Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278): implications for drug design. J. Med. Chem. 53:4295-4299.
32. Maguire, M. E., and J. A. Cowan. 2002. Magnesium chemistry and biochemistry. Biometals 15:203-210.
33. Mizrahi, V., M. T. Usdin, A. Harington, and L. R. Dudding. 1990. Site-directed mutagenesis of the conserved Asp-443 and Asp-498 carboxy-terminal residues of HIV-1 reverse transcriptase. Nucleic Acids Res. 18:5359-5363.
34. Navaza, J. 1993. On the computation of the fast rotation function. Acta Crystallogr. D Biol. Crystallogr. 49:588-591.
35. Nowotny, M., et al. 2008. Specific recognition of RNA/DNA hybrid and enhancement of human RNase H1 activity by HBD. EMBO J. 27:1172-1181. (Pubitemid 351508154)
36. Nowotny, M., S. A. Gaidamakov, R. J. Crouch, and W. Yang. 2005. Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis. Cell 121:1005-1016. (Pubitemid 40884393)
37. Nowotny, M., et al. 2007. Structure of human RNase H1 complexed with an RNA/DNA hybrid: insight into HIV reverse transcription. Mol. Cell 28:264-276. (Pubitemid 47599996)
38. Nowotny, M., and W. Yang. 2006. Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product release. EMBO J. 25:1924-1933.
39. Otwinowski, Z. M., and W. Minor. 1997. Processing of X-ray diffraction data collection in oscillation mode, p. 307-326. In C. W. Carter, Jr., and R. M. Sweet (ed.), Methods in enzymology, vol. 276. Academic Press, New York, NY. (Pubitemid 27085611)
40. Pari, K., G. A. Mueller, E. F. DeRose, T. W. Kirby, and R. E. London. 2003. Solution structure of the RNase H domain of the HIV-1 reverse transcriptase in the presence of magnesium. Biochemistry 42:639-650.
41. Parniak, M. A., K. L. Min, S. R. Budihas, S. F. Le Grice, and J. A. Beutler. 2003. A fluorescence-based high-throughput screening assay for inhibitors of human immunodeficiency virus-1 reverse transcriptase-associated ribonuclease H activity. Anal. Biochem. 322:33-39.
42. Rausch, J. W., and S. F. Le Grice. 2004. 'Binding, bending and bonding': polypurine tract-primed initiation of plus-strand DNA synthesis in human immunodeficiency virus. Int. J. Biochem. Cell Biol. 36:1752-1766.
43. Rausch, J. W., B. K. Sathyanarayana, M. K. Bona, and S. F. Le Grice. 2000. Probing contacts between the ribonuclease H domain of HIV-1 reverse transcriptase and nucleic acid by site-specific photocross-linking. J. Biol. Chem. 275:16015-16022.
44. Ren, J., and D. K. Stammers. 2008. Structural basis for drug resistance mechanisms for non-nucleoside inhibitors of HIV reverse transcriptase. Virus Res. 134:157-170.
45. Sarafianos, S. G., et al. 2001. Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA. EMBO J. 20:1449-1461. (Pubitemid 32233984)
46. Shaw-Reid, C. A., et al. 2003. Inhibition of HIV-1 ribonuclease H by a novel diketo acid, 4-[5-(benzoylamino)thien-2-yl]-2,4-dioxobutanoic acid. J. Biol. Chem. 278:2777-2780.
47. Smith, J. S., and M. J. Roth. 1993. Purification and characterization of an active human immunodeficiency virus type 1 RNase H domain. J. Virol. 67:4037-4049.
48. Stahl, S. J., J. D. Kaufman, S. Vikic-Topic, R. J. Crouch, and P. T. Wingfield. 1994. Construction of an enzymatically active ribonuclease H domain of human immunodeficiency virus type 1 reverse transcriptase. Protein Eng. 7:1103-1108.
49. Stammers, D. K., et al. 1991. Rapid purification and characterisation of HIV-1 reverse transcriptase and RNaseH engineered to incorporate a C-terminal tripeptide alpha-tubulin epitope. FEBS Lett. 283:298-302.
50. Steitz, T. A., S. J. Smerdon, J. Jager, and C. M. Joyce. 1994. A unified polymerase mechanism for nonhomologous DNA and RNA polymerases. Science 266:2022-2025.
51. Su, H. P., et al. 2010. Structural basis for the inhibition of RNase H activity of HIV-1 reverse transcriptase by RNase H active site-directed inhibitors. J. Virol. 84:7625-7633.
52. Summa, V., et al. 2008. Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection. J. Med. Chem. 51:5843-5855.
53. Takada, K., et al. 2007. An HIV RNase H inhibitory 1,3,4,5- tetragalloylapiitol from the African plant Hylodendron gabunensis. J. Nat. Prod. 70:1647-1649.
54. Tanese, N., A. Telesnitsky, and S. P. Goff. 1991. Abortive reverse transcription by mutants of Moloney murine leukemia virus deficient in the reverse transcriptase-associated RNase H function. J. Virol. 65:4387-4397.
55. Telesnitsky, A., and S. P. Goff. 1993. Two defective forms of reverse transcriptase can complement to restore retroviral infectivity. EMBO J. 12:4433-4438.
56. Tisdale, M., T. Schulze, B. A. Larder, and K. Moelling. 1991. Mutations within the RNase H domain of human immunodeficiency virus type 1 reverse transcriptase abolish virus infectivity. J. Gen. Virol. 72(Pt. 1):59-66.
57. Tramontano, E. 2006. HIV-1 RNase H: recent progress in an exciting, yet little explored, drug target. Mini Rev. Med. Chem. 6:727-737.
58. Tramontano, E., et al. 2005. 6-[1-(4-Fluorophenyl)methyl-1H-pyrrol-2-yl)] -2,4-dioxo-5-hexenoic acid ethyl ester, a novel diketo acid derivative which selectively inhibits the HIV-1 viral replication in cell culture and the ribonuclease H activity in vitro. Antiviral Res. 65:117-124. (Pubitemid 40222288)
59. Tumey, L. N., et al. 2005. The identification and optimization of a N-hydroxy urea series of flap endonuclease 1 inhibitors. Bioorg. Med. Chem. Lett. 15:277-281.
60. Wendeler, M., et al. 2008. Vinylogous ureas as a novel class of inhibitors of reverse transcriptase-associated ribonuclease H activity. ACS Chem. Biol. 3:635-644.
61. White, K. L., et al. 2005. A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. AIDS 19:1751-1760. (Pubitemid 41546593)